Heidi Splete

Health-related social needs and medical financial hardship are associated with increased risk of mortality in adult cancer survivors, based on data from more than 10,000 individuals.

Little is known about the specific association between health-related social needs (HRSNs) and mortality risk even though HRSNs, defined as challenges in affording food, housing, and other necessities of daily living, are potential challenges for cancer survivors, wrote Zhiyuan Zheng, PhD, of the American Cancer Society, Atlanta, and colleagues.

A 2020 study by Dr. Zheng and colleagues published in the Journal of the National Comprehensive Cancer Network (NCCN) showed that food insecurity and financial worries had a negative impact on cancer survivorship. In the new study, published in Cancer, the researchers identified cancer survivors using the 2013-2018 National Health Interview Survey (NHIS) and the NHIS Mortality File through December 31, 2019. The researchers examined mortality using the data from the Centers for Disease Control and Prevention’s National Death Index (NDI) through December 31, 2019, which links to the National Health Interview Survey Data used in the study.

Individuals’ HRSNs were categorized into three groups: severe, moderate, and minor/none. HRSNs included food insecurity and nonmedical financial concerns, such as housing costs (rent, mortgage). Medical financial hardship included material, psychological, and behavioral domains and was divided into three groups: 2-3 domains, 1 domain, or 0 domains.
 

What Are the Potential Financial Implications of this Research?

The high costs of cancer care often cause medical financial hardships for cancer survivors, and expenses also may cause psychological distress and nonmedical financial hardship as survivors try to make ends meet while facing medical bills, wrote Dr. Zheng and colleagues.

Policy makers are increasingly interested in adding HRSNs to insurance coverage; recent guidance from the Centers for Medicare & Medicaid Services (CMS) allows individual states to apply to provide nutrition and housing supports through state Medicaid programs, according to authors of a 2023 article published in JAMA Health Forum.

The new study adds to the understanding of how HRSNs impact people with cancer by examining the association with mortality risk, Yelak Biru, MSc, president and chief executive officer of the International Myeloma Foundation, said in an interview.

“This is a key area of study for addressing the disparities in treatments and outcomes that result in inequities,” said Mr. Biru, a patient advocate and multiple myeloma survivor who was not involved in the study.
 

What Does the New Study Show?

The new study characterized HRSNs in 5,855 adult cancer survivors aged 18-64 years and 5,918 aged 65-79 years. In the 18- to 64-year-old group, 25.5% reported moderate levels of HRSNs, and 18.3% reported severe HRSNs. In patients aged 65-79 years, 15.6% and 6.6% reported moderate HRSNs and severe HRSNs, respectively.

Severe HRSN was significantly associated with higher mortality risk in an adjusted analysis in patients aged 18-64 years (hazard ratio 2.00, P < .001).

Among adults aged 65-79 years, severe HRSN was not associated with higher mortality risk; however, in this older age group, those with 2-3 domains of medical financial hardship had significantly increased mortality risk compared with adults aged 65-79 years with zero domains of medical financial hardship (HR 1.58, P = .007).

Although the findings that HRSNs were associated with increased mortality risk, especially in the younger group, were not surprising, they serve as a call to action to address how HRSNs are contributing to cancer mortality, Mr. Biru said in an interview. “HRSNs, like food or housing insecurity, can lead to patients being unable to undergo the best treatment approach for their cancer,” he said.
 

What Are the Limitations and Research Gaps?

The study findings were limited by several factors including the use of self-reports to measure medical financial hardship, food insecurity, and nonmedical financial concerns in the NHIS, the researchers wrote in their discussion. More research with longer follow-up time beyond 1-5 years is needed, wrote Dr. Zheng and colleagues.

Studies also are needed to illustrate how patient navigation can help prevent patients from falling through the cracks with regard to social needs and financial hardships, Mr. Biru told this news organization.

Other areas for research include how addressing social needs affects health outcomes and whether programs designed to address social needs are effective, he said.

“Finally, qualitative research is needed to capture the lived experiences of cancer survivors facing these challenges. This knowledge can inform the development of more patient-centered interventions and policies that effectively address the social determinants of health and improve overall outcomes for all cancer survivors,” Mr. Biru said.
 

What Is the Takeaway Message for Clinicians?

HRSNs and financial hardship are significantly associated with increased risk of mortality in adult cancer survivors, Dr. Zheng and colleagues concluded. Looking ahead, comprehensive assessment of HRSNs and financial hardship may help clinicians connect patients with relevant services to mitigate the social and financial impacts of cancer, they wrote.

“The takeaway message for oncologists in practice is that addressing [HRSNs] and financial hardship is crucial for providing comprehensive and equitable cancer care,” Mr. Biru said during his interview.

“The impact of social determinants of health on cancer outcomes cannot be ignored, and oncologists play a vital role in identifying and addressing these needs,” he said. Sensitive, discussion-based screenings are needed to identify core needs such as food and transportation, but clinicians also can consider broader social factors and work with a team to connect patients to appropriate resources, he added.

“By recognizing the importance of HRSN screening and taking proactive steps to address these needs, oncologists can contribute to improving health outcomes, reducing healthcare disparities, and providing more equitable cancer care for their patients,” he said.
 

What Other Guidance Is Available?

“High-quality cancer care requires treating the whole person; measuring and addressing anything in their life that could result in poorer health outcomes is a key component of comprehensive care,” Mr. Biru emphasized.

In September 2023, the National Comprehensive Cancer Network (NCCN) convened a working group cochaired by Mr. Biru that developed recommendations for how oncology practices should routinely measure HRSNs (NCCN.org/social-needs).

“The working group proposed that every cancer patient be assessed for food, transportation access, and financial and housing security at least once a year, and be reassessed at every care transition point as well,” Mr. Biru said. Such screenings should include follow-up to connect patients with services to address any HRSNs they are experiencing, he added.

Lead author Dr. Zheng is employed by the American Cancer Society, which as a nonprofit receives funds from the public through fundraising and contributions, as well as some support from corporations and industry to support its mission programs and services. Mr. Biru had no financial conflicts to disclose.

Health-related social needs and medical financial hardship are associated with increased risk of mortality in adult cancer survivors, based on data from more than 10,000 individuals.

Little is known about the specific association between health-related social needs (HRSNs) and mortality risk even though HRSNs, defined as challenges in affording food, housing, and other necessities of daily living, are potential challenges for cancer survivors, wrote Zhiyuan Zheng, PhD, of the American Cancer Society, Atlanta, and colleagues.

A 2020 study by Dr. Zheng and colleagues published in the Journal of the National Comprehensive Cancer Network (NCCN) showed that food insecurity and financial worries had a negative impact on cancer survivorship. In the new study, published in Cancer, the researchers identified cancer survivors using the 2013-2018 National Health Interview Survey (NHIS) and the NHIS Mortality File through December 31, 2019. The researchers examined mortality using the data from the Centers for Disease Control and Prevention’s National Death Index (NDI) through December 31, 2019, which links to the National Health Interview Survey Data used in the study.

Individuals’ HRSNs were categorized into three groups: severe, moderate, and minor/none. HRSNs included food insecurity and nonmedical financial concerns, such as housing costs (rent, mortgage). Medical financial hardship included material, psychological, and behavioral domains and was divided into three groups: 2-3 domains, 1 domain, or 0 domains.
 

What Are the Potential Financial Implications of this Research?

The high costs of cancer care often cause medical financial hardships for cancer survivors, and expenses also may cause psychological distress and nonmedical financial hardship as survivors try to make ends meet while facing medical bills, wrote Dr. Zheng and colleagues.

Policy makers are increasingly interested in adding HRSNs to insurance coverage; recent guidance from the Centers for Medicare & Medicaid Services (CMS) allows individual states to apply to provide nutrition and housing supports through state Medicaid programs, according to authors of a 2023 article published in JAMA Health Forum.

The new study adds to the understanding of how HRSNs impact people with cancer by examining the association with mortality risk, Yelak Biru, MSc, president and chief executive officer of the International Myeloma Foundation, said in an interview.

“This is a key area of study for addressing the disparities in treatments and outcomes that result in inequities,” said Mr. Biru, a patient advocate and multiple myeloma survivor who was not involved in the study.
 

What Does the New Study Show?

The new study characterized HRSNs in 5,855 adult cancer survivors aged 18-64 years and 5,918 aged 65-79 years. In the 18- to 64-year-old group, 25.5% reported moderate levels of HRSNs, and 18.3% reported severe HRSNs. In patients aged 65-79 years, 15.6% and 6.6% reported moderate HRSNs and severe HRSNs, respectively.

Severe HRSN was significantly associated with higher mortality risk in an adjusted analysis in patients aged 18-64 years (hazard ratio 2.00, P < .001).

Among adults aged 65-79 years, severe HRSN was not associated with higher mortality risk; however, in this older age group, those with 2-3 domains of medical financial hardship had significantly increased mortality risk compared with adults aged 65-79 years with zero domains of medical financial hardship (HR 1.58, P = .007).

Although the findings that HRSNs were associated with increased mortality risk, especially in the younger group, were not surprising, they serve as a call to action to address how HRSNs are contributing to cancer mortality, Mr. Biru said in an interview. “HRSNs, like food or housing insecurity, can lead to patients being unable to undergo the best treatment approach for their cancer,” he said.
 

What Are the Limitations and Research Gaps?

The study findings were limited by several factors including the use of self-reports to measure medical financial hardship, food insecurity, and nonmedical financial concerns in the NHIS, the researchers wrote in their discussion. More research with longer follow-up time beyond 1-5 years is needed, wrote Dr. Zheng and colleagues.

Studies also are needed to illustrate how patient navigation can help prevent patients from falling through the cracks with regard to social needs and financial hardships, Mr. Biru told this news organization.

Other areas for research include how addressing social needs affects health outcomes and whether programs designed to address social needs are effective, he said.

“Finally, qualitative research is needed to capture the lived experiences of cancer survivors facing these challenges. This knowledge can inform the development of more patient-centered interventions and policies that effectively address the social determinants of health and improve overall outcomes for all cancer survivors,” Mr. Biru said.
 

What Is the Takeaway Message for Clinicians?

HRSNs and financial hardship are significantly associated with increased risk of mortality in adult cancer survivors, Dr. Zheng and colleagues concluded. Looking ahead, comprehensive assessment of HRSNs and financial hardship may help clinicians connect patients with relevant services to mitigate the social and financial impacts of cancer, they wrote.

“The takeaway message for oncologists in practice is that addressing [HRSNs] and financial hardship is crucial for providing comprehensive and equitable cancer care,” Mr. Biru said during his interview.

“The impact of social determinants of health on cancer outcomes cannot be ignored, and oncologists play a vital role in identifying and addressing these needs,” he said. Sensitive, discussion-based screenings are needed to identify core needs such as food and transportation, but clinicians also can consider broader social factors and work with a team to connect patients to appropriate resources, he added.

“By recognizing the importance of HRSN screening and taking proactive steps to address these needs, oncologists can contribute to improving health outcomes, reducing healthcare disparities, and providing more equitable cancer care for their patients,” he said.
 

What Other Guidance Is Available?

“High-quality cancer care requires treating the whole person; measuring and addressing anything in their life that could result in poorer health outcomes is a key component of comprehensive care,” Mr. Biru emphasized.

In September 2023, the National Comprehensive Cancer Network (NCCN) convened a working group cochaired by Mr. Biru that developed recommendations for how oncology practices should routinely measure HRSNs (NCCN.org/social-needs).

“The working group proposed that every cancer patient be assessed for food, transportation access, and financial and housing security at least once a year, and be reassessed at every care transition point as well,” Mr. Biru said. Such screenings should include follow-up to connect patients with services to address any HRSNs they are experiencing, he added.

Lead author Dr. Zheng is employed by the American Cancer Society, which as a nonprofit receives funds from the public through fundraising and contributions, as well as some support from corporations and industry to support its mission programs and services. Mr. Biru had no financial conflicts to disclose.

Health-related social needs and medical financial hardship are associated with increased risk of mortality in adult cancer survivors, based on data from more than 10,000 individuals.

Little is known about the specific association between health-related social needs (HRSNs) and mortality risk even though HRSNs, defined as challenges in affording food, housing, and other necessities of daily living, are potential challenges for cancer survivors, wrote Zhiyuan Zheng, PhD, of the American Cancer Society, Atlanta, and colleagues.

A 2020 study by Dr. Zheng and colleagues published in the Journal of the National Comprehensive Cancer Network (NCCN) showed that food insecurity and financial worries had a negative impact on cancer survivorship. In the new study, published in Cancer, the researchers identified cancer survivors using the 2013-2018 National Health Interview Survey (NHIS) and the NHIS Mortality File through December 31, 2019. The researchers examined mortality using the data from the Centers for Disease Control and Prevention’s National Death Index (NDI) through December 31, 2019, which links to the National Health Interview Survey Data used in the study.

Individuals’ HRSNs were categorized into three groups: severe, moderate, and minor/none. HRSNs included food insecurity and nonmedical financial concerns, such as housing costs (rent, mortgage). Medical financial hardship included material, psychological, and behavioral domains and was divided into three groups: 2-3 domains, 1 domain, or 0 domains.
 

What Are the Potential Financial Implications of this Research?

The high costs of cancer care often cause medical financial hardships for cancer survivors, and expenses also may cause psychological distress and nonmedical financial hardship as survivors try to make ends meet while facing medical bills, wrote Dr. Zheng and colleagues.

Policy makers are increasingly interested in adding HRSNs to insurance coverage; recent guidance from the Centers for Medicare & Medicaid Services (CMS) allows individual states to apply to provide nutrition and housing supports through state Medicaid programs, according to authors of a 2023 article published in JAMA Health Forum.

The new study adds to the understanding of how HRSNs impact people with cancer by examining the association with mortality risk, Yelak Biru, MSc, president and chief executive officer of the International Myeloma Foundation, said in an interview.

“This is a key area of study for addressing the disparities in treatments and outcomes that result in inequities,” said Mr. Biru, a patient advocate and multiple myeloma survivor who was not involved in the study.
 

What Does the New Study Show?

The new study characterized HRSNs in 5,855 adult cancer survivors aged 18-64 years and 5,918 aged 65-79 years. In the 18- to 64-year-old group, 25.5% reported moderate levels of HRSNs, and 18.3% reported severe HRSNs. In patients aged 65-79 years, 15.6% and 6.6% reported moderate HRSNs and severe HRSNs, respectively.

Severe HRSN was significantly associated with higher mortality risk in an adjusted analysis in patients aged 18-64 years (hazard ratio 2.00, P < .001).

Among adults aged 65-79 years, severe HRSN was not associated with higher mortality risk; however, in this older age group, those with 2-3 domains of medical financial hardship had significantly increased mortality risk compared with adults aged 65-79 years with zero domains of medical financial hardship (HR 1.58, P = .007).

Although the findings that HRSNs were associated with increased mortality risk, especially in the younger group, were not surprising, they serve as a call to action to address how HRSNs are contributing to cancer mortality, Mr. Biru said in an interview. “HRSNs, like food or housing insecurity, can lead to patients being unable to undergo the best treatment approach for their cancer,” he said.
 

What Are the Limitations and Research Gaps?

The study findings were limited by several factors including the use of self-reports to measure medical financial hardship, food insecurity, and nonmedical financial concerns in the NHIS, the researchers wrote in their discussion. More research with longer follow-up time beyond 1-5 years is needed, wrote Dr. Zheng and colleagues.

Studies also are needed to illustrate how patient navigation can help prevent patients from falling through the cracks with regard to social needs and financial hardships, Mr. Biru told this news organization.

Other areas for research include how addressing social needs affects health outcomes and whether programs designed to address social needs are effective, he said.

“Finally, qualitative research is needed to capture the lived experiences of cancer survivors facing these challenges. This knowledge can inform the development of more patient-centered interventions and policies that effectively address the social determinants of health and improve overall outcomes for all cancer survivors,” Mr. Biru said.
 

What Is the Takeaway Message for Clinicians?

HRSNs and financial hardship are significantly associated with increased risk of mortality in adult cancer survivors, Dr. Zheng and colleagues concluded. Looking ahead, comprehensive assessment of HRSNs and financial hardship may help clinicians connect patients with relevant services to mitigate the social and financial impacts of cancer, they wrote.

“The takeaway message for oncologists in practice is that addressing [HRSNs] and financial hardship is crucial for providing comprehensive and equitable cancer care,” Mr. Biru said during his interview.

“The impact of social determinants of health on cancer outcomes cannot be ignored, and oncologists play a vital role in identifying and addressing these needs,” he said. Sensitive, discussion-based screenings are needed to identify core needs such as food and transportation, but clinicians also can consider broader social factors and work with a team to connect patients to appropriate resources, he added.

“By recognizing the importance of HRSN screening and taking proactive steps to address these needs, oncologists can contribute to improving health outcomes, reducing healthcare disparities, and providing more equitable cancer care for their patients,” he said.
 

What Other Guidance Is Available?

“High-quality cancer care requires treating the whole person; measuring and addressing anything in their life that could result in poorer health outcomes is a key component of comprehensive care,” Mr. Biru emphasized.

In September 2023, the National Comprehensive Cancer Network (NCCN) convened a working group cochaired by Mr. Biru that developed recommendations for how oncology practices should routinely measure HRSNs (NCCN.org/social-needs).

“The working group proposed that every cancer patient be assessed for food, transportation access, and financial and housing security at least once a year, and be reassessed at every care transition point as well,” Mr. Biru said. Such screenings should include follow-up to connect patients with services to address any HRSNs they are experiencing, he added.

Lead author Dr. Zheng is employed by the American Cancer Society, which as a nonprofit receives funds from the public through fundraising and contributions, as well as some support from corporations and industry to support its mission programs and services. Mr. Biru had no financial conflicts to disclose.

New and evolving research in locally advanced rectal cancer suggests that selective use of treatments in some patients can achieve outcomes similar to those of standard regimens, according to the chair of the Department of Radiation Oncology at Duke University School of Medicine, Durham, North Carolina.

Total neoadjuvant therapy (TNT) is the standard treatment that involves systemic chemotherapy and radiation therapy before surgery for patients with locally advanced rectal cancer, Christopher G. Willett, MD, explained, in an interview. However, recent clinical trials support several strategies for “deintensification” of TNT for patients with locally advanced rectal cancer, he said.

Some patients may not require surgery or radiation therapy, or they may not require any treatment modalities including radiation therapy, chemotherapy, and surgery, Dr. Willett continued.

However, “these patients require close surveillance post treatment to identify any recurrence that may require salvage treatment,” he added.

During a presentation at the 2024 National Comprehensive Cancer Network Annual Conference, Dr. Willett primarily discussed the following three strategies for deintensifying overall therapy for locally advanced rectal cancer:

• Selective surgical omission for patients with rectal cancer having a complete clinical response after TNT with close surveillance following treatment.
• Selective omission of radiation therapy for patients with surgery such as sphincter-sparing surgery.
• Selective omission of all treatment modalities (radiation therapy, chemotherapy and surgery). 

Does Watch and Wait Work?

Selective surgical omission, also known as a “watch and wait” or nonoperative management (NOM), involves treating patients with chemotherapy or a combination of chemo and radiation therapy but without surgery, Dr. Willett said during his presentation at the meeting.

Data from the OPRA trial published in the Journal of Clinical Oncology showed that 36% of patients who started on NOM developed tumor regrowth, most of which occurred in the first 2-3 years. Five-year disease-free survival rates were similar in patients who had total mesorectal excision (TME) upfront and those who had salvage TME procedures after tumor regrowth (61% and 62%, respectively). An update to the OPRA trial showed that the clinical outcomes persisted, and the results suggest no significant differences in disease-free survival between upfront surgery vs. watch and wait, Dr. Willett said.
 

Does Selective Omission of Radiotherapy Work?

Selective omission of radiotherapy is another option for reducing the overall treatment burden in patients with locally advanced rectal cancer, Dr. Willett. For these patients, who are at relatively low risk for recurrence, radiation along with surgery may not be needed.

Data from the FOWARC trial, published in the Journal of Clinical Oncology in 2016 and 2019, included 495 patients from 15 centers in China. In the randomized trial, the researchers found no significant difference in the primary outcome of disease-free survival between patients assigned in a 1:1:1 ratio to three arms:

• FOLFOX chemotherapy alone (a combination of chemotherapy drugs including folinic acid, fluorouracil, and oxaliplatin).
• FOLFOX plus chemoradiation.
• FU (fluorouracil)/LV (leucovorin calcium) plus chemoradiation.

Although the data were ultimately inconclusive because of potential staging bias, the findings were “promising for recommending radiation omission in these patients,” Dr. Willett said.

The larger PROSPECT study published in The New England Journal of Medicine in 2023 was similarly encouraging, he said. In this trial, 1194 patients with locally advanced rectal cancer were randomized to FOLFOX or chemoradiation prior to sphincter-sparing surgery. The two groups showed similar 5-year estimated overall survival, complete resection (R0), and pathological complete response.

“These further data support the idea that we don’t need radiotherapy anymore,” Dr. Willett said.

PROSPECT was “a very well-done trial” that also showed important patient reported outcomes, he said. At 12 months after surgery, patients in the chemoradiation group had higher scores on fatigue and neuropathy measures, but less than 15% were severe. Sexual function scores for men and women were worse in the chemoradiation group, although overall health-related quality-of-life scores were not significantly different between the groups, he noted.
 

Does Dropping Everything But Immunotherapy Work?

Research is very preliminary, but a small study of 12 patients with mismatch repair-deficit (MMRd) locally advanced rectal cancer published in The New England Journal of Medicine “lends optimism” to a personalized treatment approach via a programmed death 1 (PD-1) blockade, Dr. Willett said. The “small, but impressive numbers” showed that all 12 patients treated with dostarlimab only (an anti-PD-1 monoclonal antibody) had durable disease control at a follow-up of 6-24 months.

This option is feasible for patients with MMRd locally advanced rectal cancer, Dr. Willett said in an interview. “Patients treated with only dostarlimab (a PD-1 inhibitor) had excellent outcomes and did not require radiation therapy, chemotherapy, and surgery. This is potentially a new paradigm of treatment for MMRd rectal cancer.”

What are the Clinical Implications and Next Steps?

Patients should be carefully evaluated and selected for treatment approaches by experienced multidisciplinary teams with vigilant posttreatment surveillance, including history and physical exam, endoscopy, computed tomography (CT) of the chest, and abdomen and pelvic magnetic resonance imaging (MRI), Dr. Willett said in the interview.

Data on the treatment of patients with MMRd rectal cancer using dostarlimab and other immune checkpoint inhibitors are preliminary; more patients and further follow-up are required, he said. This treatment is applicable to only 5%-10% of patients with rectal cancer, he continued.

“There is a need for biomarkers such as circulating tumor DNA to further aid in selection and monitoring of patients with rectal cancer,” Dr. Willett said.

Other preliminary research is examining circulating tumor DNA analysis to guide adjuvant treatment for patients with resected stage II colon cancer, he noted in his presentation. Currently, ctDNA-driven therapy is not recommended by the NCCN, but more research is needed to determine whether this strategy might be applied to decision-making in rectal cancer patients, especially with watch and wait/nonoperative strategies, he said.
 

What Are the Takeaways for Deintensifying Treatment of Rectal Cancer?

The global continuum of rectal cancer clinical trials has provided significant evidence that, for select patients, the deintensification of treatment strategies may result in the avoidance of radiation and even avoidance of surgery, which can profoundly improve long-term quality of life, Al B. Benson III, MD, said in an interview.

“A critical takeaway message for clinicians who are determining which individual patient might benefit from a less intensive regimen to treat locally advanced rectal cancer is to first have a multidisciplinary consensus which should encompass review of a rectal MRI, pathology, chest and abdominal imaging, colonoscopy, as well as the patient’s clinical status including comorbidities,” said Dr. Benson, who served as chair of the NCCN Guidelines Panel for Colon/Rectal/Anal Cancers and Small Intestine Adenocarcinoma.

“The location of the rectal tumor (distal versus proximal) and clinical TNM stage also will inform the discussion as to which of the potential total neoadjuvant therapy regimens would be most optimal to reduce the risk of local recurrence and maintain long-term quality of life for the individual patient,” explained Dr. Benson, professor of medicine at Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago.

The effectiveness of less intense treatment for rectal cancer remains a work in progress, Dr. Benson said in an interview. “There is much we still do not know, such as the optimal selection of patients and the durability of this approach over time.”

Patients who undergo watch and wait require intensive follow-up, including sigmoidoscopy, digital rectal exam, and rectal MRI, to detect any evidence of local recurrence that would warrant further intervention, including possible radiation and surgery, he said. A highly skilled multidisciplinary team is a must for individuals who are potential candidates for a less intense treatment regimen, he emphasized.  

The treatment of locally advanced rectal cancer continues to evolve, but there is no question that TNT has transformed patient outcomes, including the ability to deintensify treatment for select patients, Dr. Benson said. 

However, many research gaps remain, Dr. Benson said in an interview. “For the MSI/dMMR patient who has achieved a complete response from immunotherapy we will need more long-term data to determine the durability of a complete clinical response and long-term avoidance of other interventions including radiation, chemotherapy and surgery.

“The wait and watch strategy for the much more common MSS patient also will require much longer follow-up to determine which patients are destined to recur and which are not,” he added.

“The introduction of monitoring with ctDNA determination over time offers an opportunity to streamline surveillance of patients who have completed combination therapy and for those undergoing watch and wait; however, much more information is required to determine which of the various ctDNA assays are most optimal, and the frequency and duration of ctDNA determination that will lend this approach as a standard of care,” Dr. Benson said.

Dr. Willett and Dr. Benson had no financial conflicts to disclose.

New and evolving research in locally advanced rectal cancer suggests that selective use of treatments in some patients can achieve outcomes similar to those of standard regimens, according to the chair of the Department of Radiation Oncology at Duke University School of Medicine, Durham, North Carolina.

Total neoadjuvant therapy (TNT) is the standard treatment that involves systemic chemotherapy and radiation therapy before surgery for patients with locally advanced rectal cancer, Christopher G. Willett, MD, explained, in an interview. However, recent clinical trials support several strategies for “deintensification” of TNT for patients with locally advanced rectal cancer, he said.

Some patients may not require surgery or radiation therapy, or they may not require any treatment modalities including radiation therapy, chemotherapy, and surgery, Dr. Willett continued.

However, “these patients require close surveillance post treatment to identify any recurrence that may require salvage treatment,” he added.

During a presentation at the 2024 National Comprehensive Cancer Network Annual Conference, Dr. Willett primarily discussed the following three strategies for deintensifying overall therapy for locally advanced rectal cancer:

• Selective surgical omission for patients with rectal cancer having a complete clinical response after TNT with close surveillance following treatment.
• Selective omission of radiation therapy for patients with surgery such as sphincter-sparing surgery.
• Selective omission of all treatment modalities (radiation therapy, chemotherapy and surgery). 

Does Watch and Wait Work?

Selective surgical omission, also known as a “watch and wait” or nonoperative management (NOM), involves treating patients with chemotherapy or a combination of chemo and radiation therapy but without surgery, Dr. Willett said during his presentation at the meeting.

Data from the OPRA trial published in the Journal of Clinical Oncology showed that 36% of patients who started on NOM developed tumor regrowth, most of which occurred in the first 2-3 years. Five-year disease-free survival rates were similar in patients who had total mesorectal excision (TME) upfront and those who had salvage TME procedures after tumor regrowth (61% and 62%, respectively). An update to the OPRA trial showed that the clinical outcomes persisted, and the results suggest no significant differences in disease-free survival between upfront surgery vs. watch and wait, Dr. Willett said.
 

Does Selective Omission of Radiotherapy Work?

Selective omission of radiotherapy is another option for reducing the overall treatment burden in patients with locally advanced rectal cancer, Dr. Willett. For these patients, who are at relatively low risk for recurrence, radiation along with surgery may not be needed.

Data from the FOWARC trial, published in the Journal of Clinical Oncology in 2016 and 2019, included 495 patients from 15 centers in China. In the randomized trial, the researchers found no significant difference in the primary outcome of disease-free survival between patients assigned in a 1:1:1 ratio to three arms:

• FOLFOX chemotherapy alone (a combination of chemotherapy drugs including folinic acid, fluorouracil, and oxaliplatin).
• FOLFOX plus chemoradiation.
• FU (fluorouracil)/LV (leucovorin calcium) plus chemoradiation.

Although the data were ultimately inconclusive because of potential staging bias, the findings were “promising for recommending radiation omission in these patients,” Dr. Willett said.

The larger PROSPECT study published in The New England Journal of Medicine in 2023 was similarly encouraging, he said. In this trial, 1194 patients with locally advanced rectal cancer were randomized to FOLFOX or chemoradiation prior to sphincter-sparing surgery. The two groups showed similar 5-year estimated overall survival, complete resection (R0), and pathological complete response.

“These further data support the idea that we don’t need radiotherapy anymore,” Dr. Willett said.

PROSPECT was “a very well-done trial” that also showed important patient reported outcomes, he said. At 12 months after surgery, patients in the chemoradiation group had higher scores on fatigue and neuropathy measures, but less than 15% were severe. Sexual function scores for men and women were worse in the chemoradiation group, although overall health-related quality-of-life scores were not significantly different between the groups, he noted.
 

Does Dropping Everything But Immunotherapy Work?

Research is very preliminary, but a small study of 12 patients with mismatch repair-deficit (MMRd) locally advanced rectal cancer published in The New England Journal of Medicine “lends optimism” to a personalized treatment approach via a programmed death 1 (PD-1) blockade, Dr. Willett said. The “small, but impressive numbers” showed that all 12 patients treated with dostarlimab only (an anti-PD-1 monoclonal antibody) had durable disease control at a follow-up of 6-24 months.

This option is feasible for patients with MMRd locally advanced rectal cancer, Dr. Willett said in an interview. “Patients treated with only dostarlimab (a PD-1 inhibitor) had excellent outcomes and did not require radiation therapy, chemotherapy, and surgery. This is potentially a new paradigm of treatment for MMRd rectal cancer.”

What are the Clinical Implications and Next Steps?

Patients should be carefully evaluated and selected for treatment approaches by experienced multidisciplinary teams with vigilant posttreatment surveillance, including history and physical exam, endoscopy, computed tomography (CT) of the chest, and abdomen and pelvic magnetic resonance imaging (MRI), Dr. Willett said in the interview.

Data on the treatment of patients with MMRd rectal cancer using dostarlimab and other immune checkpoint inhibitors are preliminary; more patients and further follow-up are required, he said. This treatment is applicable to only 5%-10% of patients with rectal cancer, he continued.

“There is a need for biomarkers such as circulating tumor DNA to further aid in selection and monitoring of patients with rectal cancer,” Dr. Willett said.

Other preliminary research is examining circulating tumor DNA analysis to guide adjuvant treatment for patients with resected stage II colon cancer, he noted in his presentation. Currently, ctDNA-driven therapy is not recommended by the NCCN, but more research is needed to determine whether this strategy might be applied to decision-making in rectal cancer patients, especially with watch and wait/nonoperative strategies, he said.
 

What Are the Takeaways for Deintensifying Treatment of Rectal Cancer?

The global continuum of rectal cancer clinical trials has provided significant evidence that, for select patients, the deintensification of treatment strategies may result in the avoidance of radiation and even avoidance of surgery, which can profoundly improve long-term quality of life, Al B. Benson III, MD, said in an interview.

“A critical takeaway message for clinicians who are determining which individual patient might benefit from a less intensive regimen to treat locally advanced rectal cancer is to first have a multidisciplinary consensus which should encompass review of a rectal MRI, pathology, chest and abdominal imaging, colonoscopy, as well as the patient’s clinical status including comorbidities,” said Dr. Benson, who served as chair of the NCCN Guidelines Panel for Colon/Rectal/Anal Cancers and Small Intestine Adenocarcinoma.

“The location of the rectal tumor (distal versus proximal) and clinical TNM stage also will inform the discussion as to which of the potential total neoadjuvant therapy regimens would be most optimal to reduce the risk of local recurrence and maintain long-term quality of life for the individual patient,” explained Dr. Benson, professor of medicine at Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago.

The effectiveness of less intense treatment for rectal cancer remains a work in progress, Dr. Benson said in an interview. “There is much we still do not know, such as the optimal selection of patients and the durability of this approach over time.”

Patients who undergo watch and wait require intensive follow-up, including sigmoidoscopy, digital rectal exam, and rectal MRI, to detect any evidence of local recurrence that would warrant further intervention, including possible radiation and surgery, he said. A highly skilled multidisciplinary team is a must for individuals who are potential candidates for a less intense treatment regimen, he emphasized.  

The treatment of locally advanced rectal cancer continues to evolve, but there is no question that TNT has transformed patient outcomes, including the ability to deintensify treatment for select patients, Dr. Benson said. 

However, many research gaps remain, Dr. Benson said in an interview. “For the MSI/dMMR patient who has achieved a complete response from immunotherapy we will need more long-term data to determine the durability of a complete clinical response and long-term avoidance of other interventions including radiation, chemotherapy and surgery.

“The wait and watch strategy for the much more common MSS patient also will require much longer follow-up to determine which patients are destined to recur and which are not,” he added.

“The introduction of monitoring with ctDNA determination over time offers an opportunity to streamline surveillance of patients who have completed combination therapy and for those undergoing watch and wait; however, much more information is required to determine which of the various ctDNA assays are most optimal, and the frequency and duration of ctDNA determination that will lend this approach as a standard of care,” Dr. Benson said.

Dr. Willett and Dr. Benson had no financial conflicts to disclose.

New and evolving research in locally advanced rectal cancer suggests that selective use of treatments in some patients can achieve outcomes similar to those of standard regimens, according to the chair of the Department of Radiation Oncology at Duke University School of Medicine, Durham, North Carolina.

Total neoadjuvant therapy (TNT) is the standard treatment that involves systemic chemotherapy and radiation therapy before surgery for patients with locally advanced rectal cancer, Christopher G. Willett, MD, explained, in an interview. However, recent clinical trials support several strategies for “deintensification” of TNT for patients with locally advanced rectal cancer, he said.

Some patients may not require surgery or radiation therapy, or they may not require any treatment modalities including radiation therapy, chemotherapy, and surgery, Dr. Willett continued.

However, “these patients require close surveillance post treatment to identify any recurrence that may require salvage treatment,” he added.

During a presentation at the 2024 National Comprehensive Cancer Network Annual Conference, Dr. Willett primarily discussed the following three strategies for deintensifying overall therapy for locally advanced rectal cancer:

• Selective surgical omission for patients with rectal cancer having a complete clinical response after TNT with close surveillance following treatment.
• Selective omission of radiation therapy for patients with surgery such as sphincter-sparing surgery.
• Selective omission of all treatment modalities (radiation therapy, chemotherapy and surgery). 

Does Watch and Wait Work?

Selective surgical omission, also known as a “watch and wait” or nonoperative management (NOM), involves treating patients with chemotherapy or a combination of chemo and radiation therapy but without surgery, Dr. Willett said during his presentation at the meeting.

Data from the OPRA trial published in the Journal of Clinical Oncology showed that 36% of patients who started on NOM developed tumor regrowth, most of which occurred in the first 2-3 years. Five-year disease-free survival rates were similar in patients who had total mesorectal excision (TME) upfront and those who had salvage TME procedures after tumor regrowth (61% and 62%, respectively). An update to the OPRA trial showed that the clinical outcomes persisted, and the results suggest no significant differences in disease-free survival between upfront surgery vs. watch and wait, Dr. Willett said.
 

Does Selective Omission of Radiotherapy Work?

Selective omission of radiotherapy is another option for reducing the overall treatment burden in patients with locally advanced rectal cancer, Dr. Willett. For these patients, who are at relatively low risk for recurrence, radiation along with surgery may not be needed.

Data from the FOWARC trial, published in the Journal of Clinical Oncology in 2016 and 2019, included 495 patients from 15 centers in China. In the randomized trial, the researchers found no significant difference in the primary outcome of disease-free survival between patients assigned in a 1:1:1 ratio to three arms:

• FOLFOX chemotherapy alone (a combination of chemotherapy drugs including folinic acid, fluorouracil, and oxaliplatin).
• FOLFOX plus chemoradiation.
• FU (fluorouracil)/LV (leucovorin calcium) plus chemoradiation.

Although the data were ultimately inconclusive because of potential staging bias, the findings were “promising for recommending radiation omission in these patients,” Dr. Willett said.

The larger PROSPECT study published in The New England Journal of Medicine in 2023 was similarly encouraging, he said. In this trial, 1194 patients with locally advanced rectal cancer were randomized to FOLFOX or chemoradiation prior to sphincter-sparing surgery. The two groups showed similar 5-year estimated overall survival, complete resection (R0), and pathological complete response.

“These further data support the idea that we don’t need radiotherapy anymore,” Dr. Willett said.

PROSPECT was “a very well-done trial” that also showed important patient reported outcomes, he said. At 12 months after surgery, patients in the chemoradiation group had higher scores on fatigue and neuropathy measures, but less than 15% were severe. Sexual function scores for men and women were worse in the chemoradiation group, although overall health-related quality-of-life scores were not significantly different between the groups, he noted.
 

Does Dropping Everything But Immunotherapy Work?

Research is very preliminary, but a small study of 12 patients with mismatch repair-deficit (MMRd) locally advanced rectal cancer published in The New England Journal of Medicine “lends optimism” to a personalized treatment approach via a programmed death 1 (PD-1) blockade, Dr. Willett said. The “small, but impressive numbers” showed that all 12 patients treated with dostarlimab only (an anti-PD-1 monoclonal antibody) had durable disease control at a follow-up of 6-24 months.

This option is feasible for patients with MMRd locally advanced rectal cancer, Dr. Willett said in an interview. “Patients treated with only dostarlimab (a PD-1 inhibitor) had excellent outcomes and did not require radiation therapy, chemotherapy, and surgery. This is potentially a new paradigm of treatment for MMRd rectal cancer.”

What are the Clinical Implications and Next Steps?

Patients should be carefully evaluated and selected for treatment approaches by experienced multidisciplinary teams with vigilant posttreatment surveillance, including history and physical exam, endoscopy, computed tomography (CT) of the chest, and abdomen and pelvic magnetic resonance imaging (MRI), Dr. Willett said in the interview.

Data on the treatment of patients with MMRd rectal cancer using dostarlimab and other immune checkpoint inhibitors are preliminary; more patients and further follow-up are required, he said. This treatment is applicable to only 5%-10% of patients with rectal cancer, he continued.

“There is a need for biomarkers such as circulating tumor DNA to further aid in selection and monitoring of patients with rectal cancer,” Dr. Willett said.

Other preliminary research is examining circulating tumor DNA analysis to guide adjuvant treatment for patients with resected stage II colon cancer, he noted in his presentation. Currently, ctDNA-driven therapy is not recommended by the NCCN, but more research is needed to determine whether this strategy might be applied to decision-making in rectal cancer patients, especially with watch and wait/nonoperative strategies, he said.
 

What Are the Takeaways for Deintensifying Treatment of Rectal Cancer?

The global continuum of rectal cancer clinical trials has provided significant evidence that, for select patients, the deintensification of treatment strategies may result in the avoidance of radiation and even avoidance of surgery, which can profoundly improve long-term quality of life, Al B. Benson III, MD, said in an interview.

“A critical takeaway message for clinicians who are determining which individual patient might benefit from a less intensive regimen to treat locally advanced rectal cancer is to first have a multidisciplinary consensus which should encompass review of a rectal MRI, pathology, chest and abdominal imaging, colonoscopy, as well as the patient’s clinical status including comorbidities,” said Dr. Benson, who served as chair of the NCCN Guidelines Panel for Colon/Rectal/Anal Cancers and Small Intestine Adenocarcinoma.

“The location of the rectal tumor (distal versus proximal) and clinical TNM stage also will inform the discussion as to which of the potential total neoadjuvant therapy regimens would be most optimal to reduce the risk of local recurrence and maintain long-term quality of life for the individual patient,” explained Dr. Benson, professor of medicine at Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago.

The effectiveness of less intense treatment for rectal cancer remains a work in progress, Dr. Benson said in an interview. “There is much we still do not know, such as the optimal selection of patients and the durability of this approach over time.”

Patients who undergo watch and wait require intensive follow-up, including sigmoidoscopy, digital rectal exam, and rectal MRI, to detect any evidence of local recurrence that would warrant further intervention, including possible radiation and surgery, he said. A highly skilled multidisciplinary team is a must for individuals who are potential candidates for a less intense treatment regimen, he emphasized.  

The treatment of locally advanced rectal cancer continues to evolve, but there is no question that TNT has transformed patient outcomes, including the ability to deintensify treatment for select patients, Dr. Benson said. 

However, many research gaps remain, Dr. Benson said in an interview. “For the MSI/dMMR patient who has achieved a complete response from immunotherapy we will need more long-term data to determine the durability of a complete clinical response and long-term avoidance of other interventions including radiation, chemotherapy and surgery.

“The wait and watch strategy for the much more common MSS patient also will require much longer follow-up to determine which patients are destined to recur and which are not,” he added.

“The introduction of monitoring with ctDNA determination over time offers an opportunity to streamline surveillance of patients who have completed combination therapy and for those undergoing watch and wait; however, much more information is required to determine which of the various ctDNA assays are most optimal, and the frequency and duration of ctDNA determination that will lend this approach as a standard of care,” Dr. Benson said.

Dr. Willett and Dr. Benson had no financial conflicts to disclose.

Approximately one third of pregnant individuals with syphilis were inadequately treated or not treated for syphilis despite receiving timely prenatal care, based on data from nearly 1500 patients.

Although congenital syphilis is preventable with treatment before or early in pregnancy, data from the Centers for Disease Control and Prevention (CDC) show a doubling of syphilis rates in the United States between 2018 and 2021 wrote Ayzsa Tannis, MPH, of the Centers for Disease Control and Prevention, Atlanta, and colleagues.

To better understand factors contributing to inadequate syphilis treatment during pregnancy, the researchers examined data from 1476 individuals with syphilis during pregnancy. The study population came from six jurisdictions that participated in the Surveillance for Emerging Threats to Pregnant People and Infants Network, and sources included case investigations, medical records, and links between laboratory data and vital records.

The researchers characterized the status of syphilis during pregnancy as adequate, inadequate, or not treated based on the CDC’s Sexually Transmitted Infections Treatment Guidelines, 2021. Prenatal care was defined as timely (at least 30 days prior to pregnancy outcome), nontimely (less than 30 days before pregnancy outcome), and no prenatal care. The findings were published in Obstetrics & Gynecology.

Of the 1476 individuals studied, 855 (57.9%) were adequately treated for syphilis and 621 (42.1%) were inadequately or not treated.

Overall, 82% of the study population received timely prenatal care. However, 32.1% of those who received timely prenatal care were inadequately treated, including 14.8% who received no syphilis treatment. Individuals with nontimely or no prenatal care were significantly more likely to receive inadequate or no treatment for syphilis than those who received timely care (risk ratio, 2.50 and 2.73, respectively).

The findings were consistent with previous studies of missed opportunities for prevention and treatment, the researchers noted. Factors behind nontimely treatment (less than 30 days before pregnancy outcome) may include intermittent shortages of benzathine penicillin G, the standard treatment for syphilis, as well as the lack of time and administrative support for clinicians to communicate with patients and health departments, and to expedite treatment, the researchers wrote.

The results were limited by several factors including the use of data from six US jurisdictions that may not generalize to other areas, the variations in reporting years for the different jurisdictions, and variation in mandates for syphilis screening during pregnancy, the researchers noted.

More research is needed to improve syphilis testing itself, and to develop more treatment options, the researchers concluded. Partnerships among public health, patient advocacy groups, prenatal care clinicians, and other clinicians outside the prenatal care setting also are needed for effective intervention in pregnant individuals with syphilis, they said.

The study was carried out as part of the regular work of the CDC, supported by the Epidemiology and Laboratory Capacity for Prevention and Control of Emerging Infectious Diseases Cooperative Agreement and through contractual mechanisms including the Local Health Department Initiative to Chickasaw Health Consulting. The researchers had no financial conflicts to disclose.

Approximately one third of pregnant individuals with syphilis were inadequately treated or not treated for syphilis despite receiving timely prenatal care, based on data from nearly 1500 patients.

Although congenital syphilis is preventable with treatment before or early in pregnancy, data from the Centers for Disease Control and Prevention (CDC) show a doubling of syphilis rates in the United States between 2018 and 2021 wrote Ayzsa Tannis, MPH, of the Centers for Disease Control and Prevention, Atlanta, and colleagues.

To better understand factors contributing to inadequate syphilis treatment during pregnancy, the researchers examined data from 1476 individuals with syphilis during pregnancy. The study population came from six jurisdictions that participated in the Surveillance for Emerging Threats to Pregnant People and Infants Network, and sources included case investigations, medical records, and links between laboratory data and vital records.

The researchers characterized the status of syphilis during pregnancy as adequate, inadequate, or not treated based on the CDC’s Sexually Transmitted Infections Treatment Guidelines, 2021. Prenatal care was defined as timely (at least 30 days prior to pregnancy outcome), nontimely (less than 30 days before pregnancy outcome), and no prenatal care. The findings were published in Obstetrics & Gynecology.

Of the 1476 individuals studied, 855 (57.9%) were adequately treated for syphilis and 621 (42.1%) were inadequately or not treated.

Overall, 82% of the study population received timely prenatal care. However, 32.1% of those who received timely prenatal care were inadequately treated, including 14.8% who received no syphilis treatment. Individuals with nontimely or no prenatal care were significantly more likely to receive inadequate or no treatment for syphilis than those who received timely care (risk ratio, 2.50 and 2.73, respectively).

The findings were consistent with previous studies of missed opportunities for prevention and treatment, the researchers noted. Factors behind nontimely treatment (less than 30 days before pregnancy outcome) may include intermittent shortages of benzathine penicillin G, the standard treatment for syphilis, as well as the lack of time and administrative support for clinicians to communicate with patients and health departments, and to expedite treatment, the researchers wrote.

The results were limited by several factors including the use of data from six US jurisdictions that may not generalize to other areas, the variations in reporting years for the different jurisdictions, and variation in mandates for syphilis screening during pregnancy, the researchers noted.

More research is needed to improve syphilis testing itself, and to develop more treatment options, the researchers concluded. Partnerships among public health, patient advocacy groups, prenatal care clinicians, and other clinicians outside the prenatal care setting also are needed for effective intervention in pregnant individuals with syphilis, they said.

The study was carried out as part of the regular work of the CDC, supported by the Epidemiology and Laboratory Capacity for Prevention and Control of Emerging Infectious Diseases Cooperative Agreement and through contractual mechanisms including the Local Health Department Initiative to Chickasaw Health Consulting. The researchers had no financial conflicts to disclose.

Approximately one third of pregnant individuals with syphilis were inadequately treated or not treated for syphilis despite receiving timely prenatal care, based on data from nearly 1500 patients.

Although congenital syphilis is preventable with treatment before or early in pregnancy, data from the Centers for Disease Control and Prevention (CDC) show a doubling of syphilis rates in the United States between 2018 and 2021 wrote Ayzsa Tannis, MPH, of the Centers for Disease Control and Prevention, Atlanta, and colleagues.

To better understand factors contributing to inadequate syphilis treatment during pregnancy, the researchers examined data from 1476 individuals with syphilis during pregnancy. The study population came from six jurisdictions that participated in the Surveillance for Emerging Threats to Pregnant People and Infants Network, and sources included case investigations, medical records, and links between laboratory data and vital records.

The researchers characterized the status of syphilis during pregnancy as adequate, inadequate, or not treated based on the CDC’s Sexually Transmitted Infections Treatment Guidelines, 2021. Prenatal care was defined as timely (at least 30 days prior to pregnancy outcome), nontimely (less than 30 days before pregnancy outcome), and no prenatal care. The findings were published in Obstetrics & Gynecology.

Of the 1476 individuals studied, 855 (57.9%) were adequately treated for syphilis and 621 (42.1%) were inadequately or not treated.

Overall, 82% of the study population received timely prenatal care. However, 32.1% of those who received timely prenatal care were inadequately treated, including 14.8% who received no syphilis treatment. Individuals with nontimely or no prenatal care were significantly more likely to receive inadequate or no treatment for syphilis than those who received timely care (risk ratio, 2.50 and 2.73, respectively).

The findings were consistent with previous studies of missed opportunities for prevention and treatment, the researchers noted. Factors behind nontimely treatment (less than 30 days before pregnancy outcome) may include intermittent shortages of benzathine penicillin G, the standard treatment for syphilis, as well as the lack of time and administrative support for clinicians to communicate with patients and health departments, and to expedite treatment, the researchers wrote.

The results were limited by several factors including the use of data from six US jurisdictions that may not generalize to other areas, the variations in reporting years for the different jurisdictions, and variation in mandates for syphilis screening during pregnancy, the researchers noted.

More research is needed to improve syphilis testing itself, and to develop more treatment options, the researchers concluded. Partnerships among public health, patient advocacy groups, prenatal care clinicians, and other clinicians outside the prenatal care setting also are needed for effective intervention in pregnant individuals with syphilis, they said.

The study was carried out as part of the regular work of the CDC, supported by the Epidemiology and Laboratory Capacity for Prevention and Control of Emerging Infectious Diseases Cooperative Agreement and through contractual mechanisms including the Local Health Department Initiative to Chickasaw Health Consulting. The researchers had no financial conflicts to disclose.

TOPLINE:

Exposure to furan, a chemical present in agricultural products, stabilizers, pharmaceuticals, and heat-processed foods, shows a significant positive correlation with the prevalence and respiratory mortality of chronic obstructive pulmonary disease (COPD).

METHODOLOGY:

• The researchers reviewed data from the National Health and Nutrition Examination Survey database from 2013 to 2018 and identified 270 adults with a diagnosis of COPD and 7212 without.
• Exposure to furan was based on blood furan levels, and participants were divided into five groups on the basis of quartiles of log10-transformed blood furan levels.
• The researchers used a restricted cubic spline analysis to examine the association between COPD risk and blood furan levels and mediating analysis to explore the impact of inflammation.
• The primary outcome of the study was respiratory mortality.

TAKEAWAY:

• Ten COPD patients died of respiratory diseases; adjusted analysis showed a positive correlation between log10-transformed blood furan levels and respiratory mortality in COPD patients (hazard ratio, 41.00, P = .003).
• In a logistic regression analysis, log10-transformed blood furan levels were significantly associated with increased risk for COPD; individuals in the fifth quartile had significantly increased risk compared with the first quartile (odds ratio, 4.47; P = .006).
• COPD demonstrated a significant positive association with monocytes, neutrophils, and basophils, which showed mediated proportions of 8.73%, 20.90%, and 10.94%, respectively, in the relationship between furan exposure and prevalence of COPD (P < .05 for all).

IN PRACTICE:

“The implication [of the findings] is that reducing exposure to furan in the environment could potentially lower the incidence of COPD and improve the prognosis for COPD patients,” but large-scale prospective cohort studies are needed, the researchers wrote in their conclusion.

SOURCE:

The lead author of the study was Di Sun, MD, of Capital Medical University, Beijing, China. The study was published online in BMC Public Health.

LIMITATIONS:

The cross-sectional design prevented establishment of a causal relationship between furan exposure and COPD; lack of data on the conditions of furan exposure and the reliance on self-reports for COPD diagnosis were among the factors that limited the study findings.

DISCLOSURES:

The study was supported by the High Level Public Health Technology Talent Construction Project and Reform and Development Program of Beijing Institute of Respiratory Medicine. The researchers had no financial conflicts to disclose.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Exposure to furan, a chemical present in agricultural products, stabilizers, pharmaceuticals, and heat-processed foods, shows a significant positive correlation with the prevalence and respiratory mortality of chronic obstructive pulmonary disease (COPD).

METHODOLOGY:

• The researchers reviewed data from the National Health and Nutrition Examination Survey database from 2013 to 2018 and identified 270 adults with a diagnosis of COPD and 7212 without.
• Exposure to furan was based on blood furan levels, and participants were divided into five groups on the basis of quartiles of log10-transformed blood furan levels.
• The researchers used a restricted cubic spline analysis to examine the association between COPD risk and blood furan levels and mediating analysis to explore the impact of inflammation.
• The primary outcome of the study was respiratory mortality.

TAKEAWAY:

• Ten COPD patients died of respiratory diseases; adjusted analysis showed a positive correlation between log10-transformed blood furan levels and respiratory mortality in COPD patients (hazard ratio, 41.00, P = .003).
• In a logistic regression analysis, log10-transformed blood furan levels were significantly associated with increased risk for COPD; individuals in the fifth quartile had significantly increased risk compared with the first quartile (odds ratio, 4.47; P = .006).
• COPD demonstrated a significant positive association with monocytes, neutrophils, and basophils, which showed mediated proportions of 8.73%, 20.90%, and 10.94%, respectively, in the relationship between furan exposure and prevalence of COPD (P < .05 for all).

IN PRACTICE:

“The implication [of the findings] is that reducing exposure to furan in the environment could potentially lower the incidence of COPD and improve the prognosis for COPD patients,” but large-scale prospective cohort studies are needed, the researchers wrote in their conclusion.

SOURCE:

The lead author of the study was Di Sun, MD, of Capital Medical University, Beijing, China. The study was published online in BMC Public Health.

LIMITATIONS:

The cross-sectional design prevented establishment of a causal relationship between furan exposure and COPD; lack of data on the conditions of furan exposure and the reliance on self-reports for COPD diagnosis were among the factors that limited the study findings.

DISCLOSURES:

The study was supported by the High Level Public Health Technology Talent Construction Project and Reform and Development Program of Beijing Institute of Respiratory Medicine. The researchers had no financial conflicts to disclose.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Exposure to furan, a chemical present in agricultural products, stabilizers, pharmaceuticals, and heat-processed foods, shows a significant positive correlation with the prevalence and respiratory mortality of chronic obstructive pulmonary disease (COPD).

METHODOLOGY:

• The researchers reviewed data from the National Health and Nutrition Examination Survey database from 2013 to 2018 and identified 270 adults with a diagnosis of COPD and 7212 without.
• Exposure to furan was based on blood furan levels, and participants were divided into five groups on the basis of quartiles of log10-transformed blood furan levels.
• The researchers used a restricted cubic spline analysis to examine the association between COPD risk and blood furan levels and mediating analysis to explore the impact of inflammation.
• The primary outcome of the study was respiratory mortality.

TAKEAWAY:

• Ten COPD patients died of respiratory diseases; adjusted analysis showed a positive correlation between log10-transformed blood furan levels and respiratory mortality in COPD patients (hazard ratio, 41.00, P = .003).
• In a logistic regression analysis, log10-transformed blood furan levels were significantly associated with increased risk for COPD; individuals in the fifth quartile had significantly increased risk compared with the first quartile (odds ratio, 4.47; P = .006).
• COPD demonstrated a significant positive association with monocytes, neutrophils, and basophils, which showed mediated proportions of 8.73%, 20.90%, and 10.94%, respectively, in the relationship between furan exposure and prevalence of COPD (P < .05 for all).

IN PRACTICE:

“The implication [of the findings] is that reducing exposure to furan in the environment could potentially lower the incidence of COPD and improve the prognosis for COPD patients,” but large-scale prospective cohort studies are needed, the researchers wrote in their conclusion.

SOURCE:

The lead author of the study was Di Sun, MD, of Capital Medical University, Beijing, China. The study was published online in BMC Public Health.

LIMITATIONS:

The cross-sectional design prevented establishment of a causal relationship between furan exposure and COPD; lack of data on the conditions of furan exposure and the reliance on self-reports for COPD diagnosis were among the factors that limited the study findings.

DISCLOSURES:

The study was supported by the High Level Public Health Technology Talent Construction Project and Reform and Development Program of Beijing Institute of Respiratory Medicine. The researchers had no financial conflicts to disclose.
 

A version of this article appeared on Medscape.com.

A drug prototype known as NZ-97 showed promise for treating pulmonary disease by stimulating growth of new stem cells to repair damaged tissue, based on data from a new proof-of-concept study.

In many pulmonary diseases, insufficient stem cells allow damage to progress, but researchers have developed a lung-targeted, drug-like small molecule to stimulate the growth of lung stem cells, according to data published in Proceedings of the National Academy of Sciences.

Michael J. Bollong, PhD, associate professor in the department of chemistry at Scripps Research, San Diego, and colleagues used ReFRAME, a drug repurposing library and database created by the Calibr-Skaggs Institute for Innovative Medicines (the drug discovery arm of Scripps Research) to test existing drugs as foundations to promote stem cell growth and repair in the lungs.

“At present, there are no drugs which promote regenerative repair of the lung,” Dr. Bollong said in an interview. “This is especially important in idiopathic pulmonary fibrosis, as this disease is driven by an insufficiency of the stem cell population of the lower airway, alveolar type 2 cells (AEC2s), to proliferate and to regenerate the gas exchange epithelium,” he said.

The researchers identified dipeptidyl peptidase 4 (DPP4) inhibitors as potential tools to help promote production of stem cells in the lower airway called AEC2s. Dysfunction of AEC2 is thought to play a key role in the pathogenesis of idiopathic pulmonary fibrosis, the researchers noted in the study. They created a new and highly soluble DPP4 inhibitor known as NZ-97 that could be administered via intratracheal injection.

In a mouse model of lung disease, NZ-97 induced the growth of AEC2 cells and improved damaged lung tissue. “Importantly, NZ-97 demonstrated good tolerability when dosed intratracheally every day in naive animals,” the researchers wrote in the study.

In addition, 1 month of treatment with 0.5 mg/kg of NZ-97 every fourth day showed no detectable changes in alveolar structure, increased inflammation, or cellular hyperplasia.

The current research “identifies a novel mechanism for promoting alveolar repair” and treating not only idiopathic pulmonary fibrosis (IPF) but potentially other pulmonary diseases, such as chronic obstructive pulmonary disease, Dr. Bollong said.

“Here we reported a drug prototype, NZ-97, a locally delivered and lung-retained molecule that inhibits DPP4 in the lumen of the lung,” Bollong explained. The NZ-97 prototype drug is chemically similar to CMR316, a new clinical drug candidate from researchers at Calibr-Skaggs that is scheduled to start a phase 1 clinical trial later in the summer of 2024, according to Dr. Bollong.

CMR316 is designed to be delivered once a week in mist form via a nebulizer. “If CMR316 demonstrates ameliorative efficacy in IPF, it could provide a novel avenue for regenerating the lung and could be added on top of standard-of-care anti-fibrotic drugs to delay or potentially even reverse disease progression,” Dr. Bollong told this news organization.

“The key challenge will be understanding if the identified regenerative mechanism will show ameliorative efficacy in a clinical trial,” Dr. Bollong said. “While we have shown effects in animal models and patient-derived cells, the degree and duration of the ameliorative effect in patients will ultimately be determined in the clinic.”

Looking ahead, the CMR316 phase 1 clinical trial is designed to evaluate safety and target engagement, Dr. Bollong said. Dr. Bollong’s lab continues to collaborate with Calibr to develop other regenerative approaches to the treatment of disease in other organs, he said.
 

Meeting the Need for Regenerative Treatment

The current study and the ongoing research into NZ-97 address the need for regenerative therapies in pulmonary disease, Dharani K. Narendra, MD, of Baylor College of Medicine, Houston, Texas, said in an interview.

“Identifying DPP4 inhibitors, particularly NZ-97, as potential agents for expanding type 2 alveolar epithelial cells (AEC2s) represents a promising therapeutic strategy to stimulate the regeneration of damaged alveolar epithelium,” she said. “The AEC2s play a crucial role in lung repair, and targeting these could potentially ameliorate various lung diseases that currently lack effective treatments,” she explained.

“DPP4 inhibitors are well-established in diabetes management and have known biological actions; however, the successful repurposing and effectiveness of NZ-97 in promoting lung repair are surprising to some extent,” said Dr. Narendra. “This surprise stems from this medication’s novel application and efficacy in a pulmonary context, showing significant potential where traditional DPP4 inhibitors required higher, potentially unsafe doses to achieve similar effects,” she said.

Should research prove successful, NZ-97 could offer substantial clinical benefits for treating pulmonary diseases such as IPF and other conditions involving alveolar damage. By enhancing AEC2 proliferation, NZ-97 may improve patient outcomes by mitigating lung damage and promoting regenerative repair, possibly reducing the dependency on more invasive treatments like lung transplantation.

More research on NZ-97 is needed in order to identify potential barriers to its use, Dr. Narendra said. “Further studies are needed to evaluate the long-term effects of NZ-97, understand its mechanisms in human lung tissue, and determine its safety and efficacy in clinical settings.”

Dr. Narendra had no financial conflicts to disclose but served on the Editorial Board of Chest Physician.
 

A version of this article appeared on Medscape.com.

A drug prototype known as NZ-97 showed promise for treating pulmonary disease by stimulating growth of new stem cells to repair damaged tissue, based on data from a new proof-of-concept study.

In many pulmonary diseases, insufficient stem cells allow damage to progress, but researchers have developed a lung-targeted, drug-like small molecule to stimulate the growth of lung stem cells, according to data published in Proceedings of the National Academy of Sciences.

Michael J. Bollong, PhD, associate professor in the department of chemistry at Scripps Research, San Diego, and colleagues used ReFRAME, a drug repurposing library and database created by the Calibr-Skaggs Institute for Innovative Medicines (the drug discovery arm of Scripps Research) to test existing drugs as foundations to promote stem cell growth and repair in the lungs.

“At present, there are no drugs which promote regenerative repair of the lung,” Dr. Bollong said in an interview. “This is especially important in idiopathic pulmonary fibrosis, as this disease is driven by an insufficiency of the stem cell population of the lower airway, alveolar type 2 cells (AEC2s), to proliferate and to regenerate the gas exchange epithelium,” he said.

The researchers identified dipeptidyl peptidase 4 (DPP4) inhibitors as potential tools to help promote production of stem cells in the lower airway called AEC2s. Dysfunction of AEC2 is thought to play a key role in the pathogenesis of idiopathic pulmonary fibrosis, the researchers noted in the study. They created a new and highly soluble DPP4 inhibitor known as NZ-97 that could be administered via intratracheal injection.

In a mouse model of lung disease, NZ-97 induced the growth of AEC2 cells and improved damaged lung tissue. “Importantly, NZ-97 demonstrated good tolerability when dosed intratracheally every day in naive animals,” the researchers wrote in the study.

In addition, 1 month of treatment with 0.5 mg/kg of NZ-97 every fourth day showed no detectable changes in alveolar structure, increased inflammation, or cellular hyperplasia.

The current research “identifies a novel mechanism for promoting alveolar repair” and treating not only idiopathic pulmonary fibrosis (IPF) but potentially other pulmonary diseases, such as chronic obstructive pulmonary disease, Dr. Bollong said.

“Here we reported a drug prototype, NZ-97, a locally delivered and lung-retained molecule that inhibits DPP4 in the lumen of the lung,” Bollong explained. The NZ-97 prototype drug is chemically similar to CMR316, a new clinical drug candidate from researchers at Calibr-Skaggs that is scheduled to start a phase 1 clinical trial later in the summer of 2024, according to Dr. Bollong.

CMR316 is designed to be delivered once a week in mist form via a nebulizer. “If CMR316 demonstrates ameliorative efficacy in IPF, it could provide a novel avenue for regenerating the lung and could be added on top of standard-of-care anti-fibrotic drugs to delay or potentially even reverse disease progression,” Dr. Bollong told this news organization.

“The key challenge will be understanding if the identified regenerative mechanism will show ameliorative efficacy in a clinical trial,” Dr. Bollong said. “While we have shown effects in animal models and patient-derived cells, the degree and duration of the ameliorative effect in patients will ultimately be determined in the clinic.”

Looking ahead, the CMR316 phase 1 clinical trial is designed to evaluate safety and target engagement, Dr. Bollong said. Dr. Bollong’s lab continues to collaborate with Calibr to develop other regenerative approaches to the treatment of disease in other organs, he said.
 

Meeting the Need for Regenerative Treatment

The current study and the ongoing research into NZ-97 address the need for regenerative therapies in pulmonary disease, Dharani K. Narendra, MD, of Baylor College of Medicine, Houston, Texas, said in an interview.

“Identifying DPP4 inhibitors, particularly NZ-97, as potential agents for expanding type 2 alveolar epithelial cells (AEC2s) represents a promising therapeutic strategy to stimulate the regeneration of damaged alveolar epithelium,” she said. “The AEC2s play a crucial role in lung repair, and targeting these could potentially ameliorate various lung diseases that currently lack effective treatments,” she explained.

“DPP4 inhibitors are well-established in diabetes management and have known biological actions; however, the successful repurposing and effectiveness of NZ-97 in promoting lung repair are surprising to some extent,” said Dr. Narendra. “This surprise stems from this medication’s novel application and efficacy in a pulmonary context, showing significant potential where traditional DPP4 inhibitors required higher, potentially unsafe doses to achieve similar effects,” she said.

Should research prove successful, NZ-97 could offer substantial clinical benefits for treating pulmonary diseases such as IPF and other conditions involving alveolar damage. By enhancing AEC2 proliferation, NZ-97 may improve patient outcomes by mitigating lung damage and promoting regenerative repair, possibly reducing the dependency on more invasive treatments like lung transplantation.

More research on NZ-97 is needed in order to identify potential barriers to its use, Dr. Narendra said. “Further studies are needed to evaluate the long-term effects of NZ-97, understand its mechanisms in human lung tissue, and determine its safety and efficacy in clinical settings.”

Dr. Narendra had no financial conflicts to disclose but served on the Editorial Board of Chest Physician.
 

A version of this article appeared on Medscape.com.

A drug prototype known as NZ-97 showed promise for treating pulmonary disease by stimulating growth of new stem cells to repair damaged tissue, based on data from a new proof-of-concept study.

In many pulmonary diseases, insufficient stem cells allow damage to progress, but researchers have developed a lung-targeted, drug-like small molecule to stimulate the growth of lung stem cells, according to data published in Proceedings of the National Academy of Sciences.

Michael J. Bollong, PhD, associate professor in the department of chemistry at Scripps Research, San Diego, and colleagues used ReFRAME, a drug repurposing library and database created by the Calibr-Skaggs Institute for Innovative Medicines (the drug discovery arm of Scripps Research) to test existing drugs as foundations to promote stem cell growth and repair in the lungs.

“At present, there are no drugs which promote regenerative repair of the lung,” Dr. Bollong said in an interview. “This is especially important in idiopathic pulmonary fibrosis, as this disease is driven by an insufficiency of the stem cell population of the lower airway, alveolar type 2 cells (AEC2s), to proliferate and to regenerate the gas exchange epithelium,” he said.

The researchers identified dipeptidyl peptidase 4 (DPP4) inhibitors as potential tools to help promote production of stem cells in the lower airway called AEC2s. Dysfunction of AEC2 is thought to play a key role in the pathogenesis of idiopathic pulmonary fibrosis, the researchers noted in the study. They created a new and highly soluble DPP4 inhibitor known as NZ-97 that could be administered via intratracheal injection.

In a mouse model of lung disease, NZ-97 induced the growth of AEC2 cells and improved damaged lung tissue. “Importantly, NZ-97 demonstrated good tolerability when dosed intratracheally every day in naive animals,” the researchers wrote in the study.

In addition, 1 month of treatment with 0.5 mg/kg of NZ-97 every fourth day showed no detectable changes in alveolar structure, increased inflammation, or cellular hyperplasia.

The current research “identifies a novel mechanism for promoting alveolar repair” and treating not only idiopathic pulmonary fibrosis (IPF) but potentially other pulmonary diseases, such as chronic obstructive pulmonary disease, Dr. Bollong said.

“Here we reported a drug prototype, NZ-97, a locally delivered and lung-retained molecule that inhibits DPP4 in the lumen of the lung,” Bollong explained. The NZ-97 prototype drug is chemically similar to CMR316, a new clinical drug candidate from researchers at Calibr-Skaggs that is scheduled to start a phase 1 clinical trial later in the summer of 2024, according to Dr. Bollong.

CMR316 is designed to be delivered once a week in mist form via a nebulizer. “If CMR316 demonstrates ameliorative efficacy in IPF, it could provide a novel avenue for regenerating the lung and could be added on top of standard-of-care anti-fibrotic drugs to delay or potentially even reverse disease progression,” Dr. Bollong told this news organization.

“The key challenge will be understanding if the identified regenerative mechanism will show ameliorative efficacy in a clinical trial,” Dr. Bollong said. “While we have shown effects in animal models and patient-derived cells, the degree and duration of the ameliorative effect in patients will ultimately be determined in the clinic.”

Looking ahead, the CMR316 phase 1 clinical trial is designed to evaluate safety and target engagement, Dr. Bollong said. Dr. Bollong’s lab continues to collaborate with Calibr to develop other regenerative approaches to the treatment of disease in other organs, he said.
 

Meeting the Need for Regenerative Treatment

The current study and the ongoing research into NZ-97 address the need for regenerative therapies in pulmonary disease, Dharani K. Narendra, MD, of Baylor College of Medicine, Houston, Texas, said in an interview.

“Identifying DPP4 inhibitors, particularly NZ-97, as potential agents for expanding type 2 alveolar epithelial cells (AEC2s) represents a promising therapeutic strategy to stimulate the regeneration of damaged alveolar epithelium,” she said. “The AEC2s play a crucial role in lung repair, and targeting these could potentially ameliorate various lung diseases that currently lack effective treatments,” she explained.

“DPP4 inhibitors are well-established in diabetes management and have known biological actions; however, the successful repurposing and effectiveness of NZ-97 in promoting lung repair are surprising to some extent,” said Dr. Narendra. “This surprise stems from this medication’s novel application and efficacy in a pulmonary context, showing significant potential where traditional DPP4 inhibitors required higher, potentially unsafe doses to achieve similar effects,” she said.

Should research prove successful, NZ-97 could offer substantial clinical benefits for treating pulmonary diseases such as IPF and other conditions involving alveolar damage. By enhancing AEC2 proliferation, NZ-97 may improve patient outcomes by mitigating lung damage and promoting regenerative repair, possibly reducing the dependency on more invasive treatments like lung transplantation.

More research on NZ-97 is needed in order to identify potential barriers to its use, Dr. Narendra said. “Further studies are needed to evaluate the long-term effects of NZ-97, understand its mechanisms in human lung tissue, and determine its safety and efficacy in clinical settings.”

Dr. Narendra had no financial conflicts to disclose but served on the Editorial Board of Chest Physician.
 

A version of this article appeared on Medscape.com.

The latest research supports immune checkpoint inhibitor therapy for clear cell and non–clear cell renal cell carcinoma, but patient selection is key to optimize outcomes, according to a medical oncologist from the Dana-Farber Cancer Institute, Boston.

Michael Serzan, MD, who works in the Lank Center for Genitourinary Oncology at the institute, stated this at the 2024 National Comprehensive Cancer Network Annual Conference, during a presentation.

A systematic review and meta-analysis published in 2022 in European Urology Open Science summarized six randomized controlled trials with a total of 5121 adult patients. In the review, the researchers found that immune checkpoint inhibitors plus vascular endothelial growth factor tyrosine kinase inhibitors (VEGF TKI) were associated with consistent improvements across all risk groups for metastatic renal cell carcinoma.

Additional newer research supports the use of immunotherapy combinations or other immunotherapy plus tyrosine kinase inhibitors as first-line or adjuvant treatments for renal cell carcinoma, Dr. Serzan said during an interview. However, more genomic and histology-directed therapies are needed, he noted.
 

Tips for Evaluating Risk When Treating Renal Cell Carcinoma?

For patients with localized clear cell renal cell carcinoma who have undergone partial or radical nephrectomy, there are several models that estimate the risk of recurrence based on pathologic tumor stage, grade, histology, invasion, and the extent of necrosis, Dr. Serzan said. These models can help guide selection of patients who may be at high risk of recurrence and, therefore, may benefit from adjuvant therapy.

For patients with metastatic clear cell renal cell carcinoma, the IMDC and MSKCC prognostic models stratify patients to favorable, intermediate, and poor risk groups based on clinical and lab factors. The IMDC risk stratification model is used as a prognostic model to stratify patients diagnosed with metastatic kidney cancer, Dr. Serzan said.
 

What Research Supports Treatments for Clear Cell and Non–Clear Cell Renal Cell Carcinoma?

The US Food and Drug Administration (FDA) approved pembrolizumab in 2021 for the adjuvant treatment of renal cell carcinoma (RCC) in patients with intermediate-risk or high-risk of recurrence after nephrectomy or after nephrectomy and resection of metastatic lesions.

Pembrolizumab is the first adjuvant therapy shown to significantly improve overall survival in these patients, Dr. Serzan said. In the KEYNOTE-564 study, published in 2024 in the Journal of Clinical Oncology, pembrolizumab demonstrated an improvement in disease free survival as well as overall survival when compared with placebo.

Several similar studies of adjuvant immune checkpoint inhibitors for renal cell carcinoma involving atezolizumab vs. placebo, nivolumab plus ipilimumab vs. placebo, and nivolumab vs. observation have not shown significant benefits in terms of disease-free survival, Dr. Serzan noted.

The current NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer (Version: 3.2024), which were updated this year, support the use of adjuvant pembrolizumab for patients with stage II, III, or IV clear cell renal cell carcinoma after partial or radical nephrectomy, he said.

Looking ahead, biomarkers are needed to understand the risk of recurrence, and which patients benefit from adjuvant pembrolizumab, Dr. Serzan added.
 

Where Do VEGF-TKIs Fit In?

VEGF is a treatment target for renal cancer, and angiogenesis inhibition with VEGF TKIs continues to be a subject for study, Dr. Serzan said. In the CABOSUN study, published in the Journal of Clinical Oncology in 2017, patients were randomized to cabozantinib or sunitinib. Progression-free survival was significantly greater in the cabozantinib group, but overall survival was similar between the groups.

In another randomized trial, the CheckMate 214 study, patients received either sunitinib or a combination of nivolumab plus ipilimumab in four doses given every 3 weeks, followed by nivolumab alone every 2 weeks, and these patients were stratified by risk, Dr. Serzan noted.

The median progression-free survival was 12.4 months in the combination group vs. 8.5 months in the sunitinib group for patients at intermediate or poor risk of recurrence. The median progression-free survival was significantly greater in sunitinib patients with favorable risk vs. combination patients with favorable risk (28.9 months vs. 12.4 months).

Overall survival was higher for all patients with combination therapy vs. sunitinib regardless of risk stratification.

Dr. Serzan reviewed the pros of VEGF/PD1 (programmed death-ligand 1) combinations as including a high response rate (generally 52%-72%) and a low rate of primary progressive disease (5%-12%), as well as favorable progression-free and overall survival and low rates of immune-related adverse events.

However, cons of this treatment include lack of data on treatment-free survival as well as the decrease in progression-free survival and overall survival hazard ratios over time and potential chronic VEGF/TKI toxicities, he said.
 

What Treatments Are Recommended for Metastatic Clear Cell Renal Cell Carcinoma Now?

Clear cell renal cell carcinoma (ccRCC) is the most prevalent histological subtype of kidney cancer, accounting for 70%-75% of cases, and these patients are prone to metastasis, recurrence, and resistance to radiotherapy and chemotherapy, according to authors of a recent review published in Frontiers in Oncology.

Dr. Serzan shared his preferred protocol for treatment-naive metastatic ccRCC patients, based on the NCCN guidelines for Kidney Cancer (Version: 3.2024) that had been updated in 2024.

For those with sarcomatoid features, he favors the use of nivolumab/ipilimumab combination, while those without sarcomatoid features, if highly symptomatic, may be treated with any of several combinations: nivolumab/ipilimumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.

For asymptomatic patients without sarcomatoid features, treatment depends on eligibility for immune checkpoint inhibitors or ipilimumab, Dr. Serzan said. His first choice for those eligible is nivolumab/ipilimumab; those not eligible for ipilimumab could receive nivolumab, pembrolizumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.

For patients not eligible for ICIs because of uncontrolled autoimmune disease, or high-dose glucocorticoids, Dr. Serzan recommended treatment with cabozantinib, lenvatinib/everolimus, pazopanib, or sunitinib.
 

What are Some Takeaway Points About Immunotherapy and Renal Cell Carcinoma?

“Immunotherapy has revolutionized treatment for renal cell carcinoma, with significant increases in overall survival, and a small but consistent cure fraction that was unimaginable 10 years ago,” Eric Jonasch, MD, of The University of Texas MD Anderson Cancer Center and vice-chair of the NCCN Guidelines Panel for Kidney Cancer, said in an interview.

However, challenges to implementing new treatments in clinical practice are ongoing, he said. The major challenges facing clinicians, patients, and their families include the cost of therapy, logistics of treatment administration, and managing toxicities, Dr. Jonasch said.  

Patient selection is key to optimize outcomes with immunotherapy, and shared decision-making is essential to ensure that choice of therapy matches patient expectations and needs — and to maintain clear and open channels of communication while patients are on therapy, Dr. Jonasch said. “In my clinic, we empower patients to take treatment breaks to manage side effects, thereby optimizing quality of life while maintaining treatment efficacy,” he said.

Although significant progress has been made in managing renal cell carcinoma, more research is needed to increase the proportion of patients cured, said Dr. Jonasch. “A clearer understanding of the determinants of response and resistance, which will be driven by information rich clinical trials, will help move us in that direction,” he said.

Dr. Serzan had no financial conflicts to disclose. Dr. Jonasch disclosed research support from AbbVie, Arrowhead, Aveo, BMS, Corvus, Merck, NiKang, ProfoundBio, and Telix, as well as honoraria from Aveo, Eisai, Exelixis, GlaxoSmithKline, Ipsen, Merck, Novartis, NiKang, and Takeda.

The latest research supports immune checkpoint inhibitor therapy for clear cell and non–clear cell renal cell carcinoma, but patient selection is key to optimize outcomes, according to a medical oncologist from the Dana-Farber Cancer Institute, Boston.

Michael Serzan, MD, who works in the Lank Center for Genitourinary Oncology at the institute, stated this at the 2024 National Comprehensive Cancer Network Annual Conference, during a presentation.

A systematic review and meta-analysis published in 2022 in European Urology Open Science summarized six randomized controlled trials with a total of 5121 adult patients. In the review, the researchers found that immune checkpoint inhibitors plus vascular endothelial growth factor tyrosine kinase inhibitors (VEGF TKI) were associated with consistent improvements across all risk groups for metastatic renal cell carcinoma.

Additional newer research supports the use of immunotherapy combinations or other immunotherapy plus tyrosine kinase inhibitors as first-line or adjuvant treatments for renal cell carcinoma, Dr. Serzan said during an interview. However, more genomic and histology-directed therapies are needed, he noted.
 

Tips for Evaluating Risk When Treating Renal Cell Carcinoma?

For patients with localized clear cell renal cell carcinoma who have undergone partial or radical nephrectomy, there are several models that estimate the risk of recurrence based on pathologic tumor stage, grade, histology, invasion, and the extent of necrosis, Dr. Serzan said. These models can help guide selection of patients who may be at high risk of recurrence and, therefore, may benefit from adjuvant therapy.

For patients with metastatic clear cell renal cell carcinoma, the IMDC and MSKCC prognostic models stratify patients to favorable, intermediate, and poor risk groups based on clinical and lab factors. The IMDC risk stratification model is used as a prognostic model to stratify patients diagnosed with metastatic kidney cancer, Dr. Serzan said.
 

What Research Supports Treatments for Clear Cell and Non–Clear Cell Renal Cell Carcinoma?

The US Food and Drug Administration (FDA) approved pembrolizumab in 2021 for the adjuvant treatment of renal cell carcinoma (RCC) in patients with intermediate-risk or high-risk of recurrence after nephrectomy or after nephrectomy and resection of metastatic lesions.

Pembrolizumab is the first adjuvant therapy shown to significantly improve overall survival in these patients, Dr. Serzan said. In the KEYNOTE-564 study, published in 2024 in the Journal of Clinical Oncology, pembrolizumab demonstrated an improvement in disease free survival as well as overall survival when compared with placebo.

Several similar studies of adjuvant immune checkpoint inhibitors for renal cell carcinoma involving atezolizumab vs. placebo, nivolumab plus ipilimumab vs. placebo, and nivolumab vs. observation have not shown significant benefits in terms of disease-free survival, Dr. Serzan noted.

The current NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer (Version: 3.2024), which were updated this year, support the use of adjuvant pembrolizumab for patients with stage II, III, or IV clear cell renal cell carcinoma after partial or radical nephrectomy, he said.

Looking ahead, biomarkers are needed to understand the risk of recurrence, and which patients benefit from adjuvant pembrolizumab, Dr. Serzan added.
 

Where Do VEGF-TKIs Fit In?

VEGF is a treatment target for renal cancer, and angiogenesis inhibition with VEGF TKIs continues to be a subject for study, Dr. Serzan said. In the CABOSUN study, published in the Journal of Clinical Oncology in 2017, patients were randomized to cabozantinib or sunitinib. Progression-free survival was significantly greater in the cabozantinib group, but overall survival was similar between the groups.

In another randomized trial, the CheckMate 214 study, patients received either sunitinib or a combination of nivolumab plus ipilimumab in four doses given every 3 weeks, followed by nivolumab alone every 2 weeks, and these patients were stratified by risk, Dr. Serzan noted.

The median progression-free survival was 12.4 months in the combination group vs. 8.5 months in the sunitinib group for patients at intermediate or poor risk of recurrence. The median progression-free survival was significantly greater in sunitinib patients with favorable risk vs. combination patients with favorable risk (28.9 months vs. 12.4 months).

Overall survival was higher for all patients with combination therapy vs. sunitinib regardless of risk stratification.

Dr. Serzan reviewed the pros of VEGF/PD1 (programmed death-ligand 1) combinations as including a high response rate (generally 52%-72%) and a low rate of primary progressive disease (5%-12%), as well as favorable progression-free and overall survival and low rates of immune-related adverse events.

However, cons of this treatment include lack of data on treatment-free survival as well as the decrease in progression-free survival and overall survival hazard ratios over time and potential chronic VEGF/TKI toxicities, he said.
 

What Treatments Are Recommended for Metastatic Clear Cell Renal Cell Carcinoma Now?

Clear cell renal cell carcinoma (ccRCC) is the most prevalent histological subtype of kidney cancer, accounting for 70%-75% of cases, and these patients are prone to metastasis, recurrence, and resistance to radiotherapy and chemotherapy, according to authors of a recent review published in Frontiers in Oncology.

Dr. Serzan shared his preferred protocol for treatment-naive metastatic ccRCC patients, based on the NCCN guidelines for Kidney Cancer (Version: 3.2024) that had been updated in 2024.

For those with sarcomatoid features, he favors the use of nivolumab/ipilimumab combination, while those without sarcomatoid features, if highly symptomatic, may be treated with any of several combinations: nivolumab/ipilimumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.

For asymptomatic patients without sarcomatoid features, treatment depends on eligibility for immune checkpoint inhibitors or ipilimumab, Dr. Serzan said. His first choice for those eligible is nivolumab/ipilimumab; those not eligible for ipilimumab could receive nivolumab, pembrolizumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.

For patients not eligible for ICIs because of uncontrolled autoimmune disease, or high-dose glucocorticoids, Dr. Serzan recommended treatment with cabozantinib, lenvatinib/everolimus, pazopanib, or sunitinib.
 

What are Some Takeaway Points About Immunotherapy and Renal Cell Carcinoma?

“Immunotherapy has revolutionized treatment for renal cell carcinoma, with significant increases in overall survival, and a small but consistent cure fraction that was unimaginable 10 years ago,” Eric Jonasch, MD, of The University of Texas MD Anderson Cancer Center and vice-chair of the NCCN Guidelines Panel for Kidney Cancer, said in an interview.

However, challenges to implementing new treatments in clinical practice are ongoing, he said. The major challenges facing clinicians, patients, and their families include the cost of therapy, logistics of treatment administration, and managing toxicities, Dr. Jonasch said.  

Patient selection is key to optimize outcomes with immunotherapy, and shared decision-making is essential to ensure that choice of therapy matches patient expectations and needs — and to maintain clear and open channels of communication while patients are on therapy, Dr. Jonasch said. “In my clinic, we empower patients to take treatment breaks to manage side effects, thereby optimizing quality of life while maintaining treatment efficacy,” he said.

Although significant progress has been made in managing renal cell carcinoma, more research is needed to increase the proportion of patients cured, said Dr. Jonasch. “A clearer understanding of the determinants of response and resistance, which will be driven by information rich clinical trials, will help move us in that direction,” he said.

Dr. Serzan had no financial conflicts to disclose. Dr. Jonasch disclosed research support from AbbVie, Arrowhead, Aveo, BMS, Corvus, Merck, NiKang, ProfoundBio, and Telix, as well as honoraria from Aveo, Eisai, Exelixis, GlaxoSmithKline, Ipsen, Merck, Novartis, NiKang, and Takeda.

The latest research supports immune checkpoint inhibitor therapy for clear cell and non–clear cell renal cell carcinoma, but patient selection is key to optimize outcomes, according to a medical oncologist from the Dana-Farber Cancer Institute, Boston.

Michael Serzan, MD, who works in the Lank Center for Genitourinary Oncology at the institute, stated this at the 2024 National Comprehensive Cancer Network Annual Conference, during a presentation.

A systematic review and meta-analysis published in 2022 in European Urology Open Science summarized six randomized controlled trials with a total of 5121 adult patients. In the review, the researchers found that immune checkpoint inhibitors plus vascular endothelial growth factor tyrosine kinase inhibitors (VEGF TKI) were associated with consistent improvements across all risk groups for metastatic renal cell carcinoma.

Additional newer research supports the use of immunotherapy combinations or other immunotherapy plus tyrosine kinase inhibitors as first-line or adjuvant treatments for renal cell carcinoma, Dr. Serzan said during an interview. However, more genomic and histology-directed therapies are needed, he noted.
 

Tips for Evaluating Risk When Treating Renal Cell Carcinoma?

For patients with localized clear cell renal cell carcinoma who have undergone partial or radical nephrectomy, there are several models that estimate the risk of recurrence based on pathologic tumor stage, grade, histology, invasion, and the extent of necrosis, Dr. Serzan said. These models can help guide selection of patients who may be at high risk of recurrence and, therefore, may benefit from adjuvant therapy.

For patients with metastatic clear cell renal cell carcinoma, the IMDC and MSKCC prognostic models stratify patients to favorable, intermediate, and poor risk groups based on clinical and lab factors. The IMDC risk stratification model is used as a prognostic model to stratify patients diagnosed with metastatic kidney cancer, Dr. Serzan said.
 

What Research Supports Treatments for Clear Cell and Non–Clear Cell Renal Cell Carcinoma?

The US Food and Drug Administration (FDA) approved pembrolizumab in 2021 for the adjuvant treatment of renal cell carcinoma (RCC) in patients with intermediate-risk or high-risk of recurrence after nephrectomy or after nephrectomy and resection of metastatic lesions.

Pembrolizumab is the first adjuvant therapy shown to significantly improve overall survival in these patients, Dr. Serzan said. In the KEYNOTE-564 study, published in 2024 in the Journal of Clinical Oncology, pembrolizumab demonstrated an improvement in disease free survival as well as overall survival when compared with placebo.

Several similar studies of adjuvant immune checkpoint inhibitors for renal cell carcinoma involving atezolizumab vs. placebo, nivolumab plus ipilimumab vs. placebo, and nivolumab vs. observation have not shown significant benefits in terms of disease-free survival, Dr. Serzan noted.

The current NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer (Version: 3.2024), which were updated this year, support the use of adjuvant pembrolizumab for patients with stage II, III, or IV clear cell renal cell carcinoma after partial or radical nephrectomy, he said.

Looking ahead, biomarkers are needed to understand the risk of recurrence, and which patients benefit from adjuvant pembrolizumab, Dr. Serzan added.
 

Where Do VEGF-TKIs Fit In?

VEGF is a treatment target for renal cancer, and angiogenesis inhibition with VEGF TKIs continues to be a subject for study, Dr. Serzan said. In the CABOSUN study, published in the Journal of Clinical Oncology in 2017, patients were randomized to cabozantinib or sunitinib. Progression-free survival was significantly greater in the cabozantinib group, but overall survival was similar between the groups.

In another randomized trial, the CheckMate 214 study, patients received either sunitinib or a combination of nivolumab plus ipilimumab in four doses given every 3 weeks, followed by nivolumab alone every 2 weeks, and these patients were stratified by risk, Dr. Serzan noted.

The median progression-free survival was 12.4 months in the combination group vs. 8.5 months in the sunitinib group for patients at intermediate or poor risk of recurrence. The median progression-free survival was significantly greater in sunitinib patients with favorable risk vs. combination patients with favorable risk (28.9 months vs. 12.4 months).

Overall survival was higher for all patients with combination therapy vs. sunitinib regardless of risk stratification.

Dr. Serzan reviewed the pros of VEGF/PD1 (programmed death-ligand 1) combinations as including a high response rate (generally 52%-72%) and a low rate of primary progressive disease (5%-12%), as well as favorable progression-free and overall survival and low rates of immune-related adverse events.

However, cons of this treatment include lack of data on treatment-free survival as well as the decrease in progression-free survival and overall survival hazard ratios over time and potential chronic VEGF/TKI toxicities, he said.
 

What Treatments Are Recommended for Metastatic Clear Cell Renal Cell Carcinoma Now?

Clear cell renal cell carcinoma (ccRCC) is the most prevalent histological subtype of kidney cancer, accounting for 70%-75% of cases, and these patients are prone to metastasis, recurrence, and resistance to radiotherapy and chemotherapy, according to authors of a recent review published in Frontiers in Oncology.

Dr. Serzan shared his preferred protocol for treatment-naive metastatic ccRCC patients, based on the NCCN guidelines for Kidney Cancer (Version: 3.2024) that had been updated in 2024.

For those with sarcomatoid features, he favors the use of nivolumab/ipilimumab combination, while those without sarcomatoid features, if highly symptomatic, may be treated with any of several combinations: nivolumab/ipilimumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.

For asymptomatic patients without sarcomatoid features, treatment depends on eligibility for immune checkpoint inhibitors or ipilimumab, Dr. Serzan said. His first choice for those eligible is nivolumab/ipilimumab; those not eligible for ipilimumab could receive nivolumab, pembrolizumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.

For patients not eligible for ICIs because of uncontrolled autoimmune disease, or high-dose glucocorticoids, Dr. Serzan recommended treatment with cabozantinib, lenvatinib/everolimus, pazopanib, or sunitinib.
 

What are Some Takeaway Points About Immunotherapy and Renal Cell Carcinoma?

“Immunotherapy has revolutionized treatment for renal cell carcinoma, with significant increases in overall survival, and a small but consistent cure fraction that was unimaginable 10 years ago,” Eric Jonasch, MD, of The University of Texas MD Anderson Cancer Center and vice-chair of the NCCN Guidelines Panel for Kidney Cancer, said in an interview.

However, challenges to implementing new treatments in clinical practice are ongoing, he said. The major challenges facing clinicians, patients, and their families include the cost of therapy, logistics of treatment administration, and managing toxicities, Dr. Jonasch said.  

Patient selection is key to optimize outcomes with immunotherapy, and shared decision-making is essential to ensure that choice of therapy matches patient expectations and needs — and to maintain clear and open channels of communication while patients are on therapy, Dr. Jonasch said. “In my clinic, we empower patients to take treatment breaks to manage side effects, thereby optimizing quality of life while maintaining treatment efficacy,” he said.

Although significant progress has been made in managing renal cell carcinoma, more research is needed to increase the proportion of patients cured, said Dr. Jonasch. “A clearer understanding of the determinants of response and resistance, which will be driven by information rich clinical trials, will help move us in that direction,” he said.

Dr. Serzan had no financial conflicts to disclose. Dr. Jonasch disclosed research support from AbbVie, Arrowhead, Aveo, BMS, Corvus, Merck, NiKang, ProfoundBio, and Telix, as well as honoraria from Aveo, Eisai, Exelixis, GlaxoSmithKline, Ipsen, Merck, Novartis, NiKang, and Takeda.

Recent cases of botulism-like illness following neurotoxin injections in nonmedical settings have prompted the American Society for Dermatologic Surgery Association (ASDSA) to call on states to increase oversight of medical care in all settings, including medical spas.

In a press release issued on April 12, the ASDSA referenced investigations in Illinois and Tennessee in which suspected counterfeit neurotoxins were associated with individuals’ symptoms resembling botulism, including several that required hospitalization. These cases “emphasize the patient safety risks associated with receiving medical procedures in unlicensed, unapproved settings without proper oversight of medical care,” the release adds.

The cases also “highlight the need for increased public protection measures, like the recommendations in the ASDSA’s “Medical Spa Safety Act” to ensure patients’ safety,” according to the press release, which notes the increasing demand for facial fillers and neuromodulators in the United States.

Enforcement is needed to ensure that all patients receive US Food and Drug Administration (FDA)-approved products “and not counterfeit products or unsafe treatments,” ASDSA president Seth L. Matarasso, MD, who practices dermatology in San Francisco, said in the press release. “Lack of regulation and enforcement has enabled many to offer medical procedures for cosmetic purposes outside of their training and expertise,” he said.

Key Takeaways

All clinicians need to understand that aesthetic procedures are medical procedures and require a level of due diligence in patient evaluation and care before, during, and after the procedure, Pooja Sodha, MD, director of the Center for Laser and Cosmetic Dermatology at George Washington University, Washington, said in an interview.

Dr. Sodha

“FDA-approved medications should only be offered, and these should be obtained through well-defined sources to ensure their safety and purity,” she said.

However, some challenges to the enforcement of safety in medical spa settings persist, Dr. Sodha told this news organization. “To my knowledge, state and federal policies providing clear and up-to-date safety and legal guidelines for aesthetic procedures performed at medical spas by registered nurses, nurse practitioners, physician assistants, and physicians are limited, and in our current medical care structure, national oversight is challenging,” she said.

A pretreatment checklist assessment, she suggested, could be helpful “to ensure patient safety and help to standardize clinical practice in nonmedical settings.”

Other challenges include a lack of clear guidelines for aesthetic providers regarding initial assessment examinations, postprocedure follow-up, and evaluation for any future medical treatment, as well as “continued ambiguity on the exact meaning of physician oversight for those sites that delegate aesthetic services and appropriate and clear guidelines on what procedures require a licensed provider to perform versus oversee the treatment,” she said.
 

Additional Guidance, Actions Needed

As for additional guidance or actions, “we may be migrating towards a system that designates and assigns clearer licenses and authorizations to perform these services and care for patients,” said Dr. Sodha. A licensing process would entail academic understanding of anatomy, pharmacology, and tissue interactions, as well as practical hands-on training that emphasizes the importance of the preprocedure consultation and postprocedure follow-up and care, she said. “Experience in caring for the unintended outcomes is vital to delivering the best care we can,” she added.

D. Sodha had no financial conflicts to disclose.
 

A version of this article appeared on Medscape.com.

Recent cases of botulism-like illness following neurotoxin injections in nonmedical settings have prompted the American Society for Dermatologic Surgery Association (ASDSA) to call on states to increase oversight of medical care in all settings, including medical spas.

In a press release issued on April 12, the ASDSA referenced investigations in Illinois and Tennessee in which suspected counterfeit neurotoxins were associated with individuals’ symptoms resembling botulism, including several that required hospitalization. These cases “emphasize the patient safety risks associated with receiving medical procedures in unlicensed, unapproved settings without proper oversight of medical care,” the release adds.

The cases also “highlight the need for increased public protection measures, like the recommendations in the ASDSA’s “Medical Spa Safety Act” to ensure patients’ safety,” according to the press release, which notes the increasing demand for facial fillers and neuromodulators in the United States.

Enforcement is needed to ensure that all patients receive US Food and Drug Administration (FDA)-approved products “and not counterfeit products or unsafe treatments,” ASDSA president Seth L. Matarasso, MD, who practices dermatology in San Francisco, said in the press release. “Lack of regulation and enforcement has enabled many to offer medical procedures for cosmetic purposes outside of their training and expertise,” he said.

Key Takeaways

All clinicians need to understand that aesthetic procedures are medical procedures and require a level of due diligence in patient evaluation and care before, during, and after the procedure, Pooja Sodha, MD, director of the Center for Laser and Cosmetic Dermatology at George Washington University, Washington, said in an interview.

Dr. Sodha

“FDA-approved medications should only be offered, and these should be obtained through well-defined sources to ensure their safety and purity,” she said.

However, some challenges to the enforcement of safety in medical spa settings persist, Dr. Sodha told this news organization. “To my knowledge, state and federal policies providing clear and up-to-date safety and legal guidelines for aesthetic procedures performed at medical spas by registered nurses, nurse practitioners, physician assistants, and physicians are limited, and in our current medical care structure, national oversight is challenging,” she said.

A pretreatment checklist assessment, she suggested, could be helpful “to ensure patient safety and help to standardize clinical practice in nonmedical settings.”

Other challenges include a lack of clear guidelines for aesthetic providers regarding initial assessment examinations, postprocedure follow-up, and evaluation for any future medical treatment, as well as “continued ambiguity on the exact meaning of physician oversight for those sites that delegate aesthetic services and appropriate and clear guidelines on what procedures require a licensed provider to perform versus oversee the treatment,” she said.
 

Additional Guidance, Actions Needed

As for additional guidance or actions, “we may be migrating towards a system that designates and assigns clearer licenses and authorizations to perform these services and care for patients,” said Dr. Sodha. A licensing process would entail academic understanding of anatomy, pharmacology, and tissue interactions, as well as practical hands-on training that emphasizes the importance of the preprocedure consultation and postprocedure follow-up and care, she said. “Experience in caring for the unintended outcomes is vital to delivering the best care we can,” she added.

D. Sodha had no financial conflicts to disclose.
 

A version of this article appeared on Medscape.com.

Recent cases of botulism-like illness following neurotoxin injections in nonmedical settings have prompted the American Society for Dermatologic Surgery Association (ASDSA) to call on states to increase oversight of medical care in all settings, including medical spas.

In a press release issued on April 12, the ASDSA referenced investigations in Illinois and Tennessee in which suspected counterfeit neurotoxins were associated with individuals’ symptoms resembling botulism, including several that required hospitalization. These cases “emphasize the patient safety risks associated with receiving medical procedures in unlicensed, unapproved settings without proper oversight of medical care,” the release adds.

The cases also “highlight the need for increased public protection measures, like the recommendations in the ASDSA’s “Medical Spa Safety Act” to ensure patients’ safety,” according to the press release, which notes the increasing demand for facial fillers and neuromodulators in the United States.

Enforcement is needed to ensure that all patients receive US Food and Drug Administration (FDA)-approved products “and not counterfeit products or unsafe treatments,” ASDSA president Seth L. Matarasso, MD, who practices dermatology in San Francisco, said in the press release. “Lack of regulation and enforcement has enabled many to offer medical procedures for cosmetic purposes outside of their training and expertise,” he said.

Key Takeaways

All clinicians need to understand that aesthetic procedures are medical procedures and require a level of due diligence in patient evaluation and care before, during, and after the procedure, Pooja Sodha, MD, director of the Center for Laser and Cosmetic Dermatology at George Washington University, Washington, said in an interview.

Dr. Sodha

“FDA-approved medications should only be offered, and these should be obtained through well-defined sources to ensure their safety and purity,” she said.

However, some challenges to the enforcement of safety in medical spa settings persist, Dr. Sodha told this news organization. “To my knowledge, state and federal policies providing clear and up-to-date safety and legal guidelines for aesthetic procedures performed at medical spas by registered nurses, nurse practitioners, physician assistants, and physicians are limited, and in our current medical care structure, national oversight is challenging,” she said.

A pretreatment checklist assessment, she suggested, could be helpful “to ensure patient safety and help to standardize clinical practice in nonmedical settings.”

Other challenges include a lack of clear guidelines for aesthetic providers regarding initial assessment examinations, postprocedure follow-up, and evaluation for any future medical treatment, as well as “continued ambiguity on the exact meaning of physician oversight for those sites that delegate aesthetic services and appropriate and clear guidelines on what procedures require a licensed provider to perform versus oversee the treatment,” she said.
 

Additional Guidance, Actions Needed

As for additional guidance or actions, “we may be migrating towards a system that designates and assigns clearer licenses and authorizations to perform these services and care for patients,” said Dr. Sodha. A licensing process would entail academic understanding of anatomy, pharmacology, and tissue interactions, as well as practical hands-on training that emphasizes the importance of the preprocedure consultation and postprocedure follow-up and care, she said. “Experience in caring for the unintended outcomes is vital to delivering the best care we can,” she added.

D. Sodha had no financial conflicts to disclose.
 

A version of this article appeared on Medscape.com.

Reported burnout among internal medicine physicians decreased over the past year based on data from Medscape’s annual survey of burnout and depression among physicians in the United States.

Approximately 80% of male internists and 85% of female internists said that their feelings of burnout and/or depression were driven by their jobs all or most of the time. The job-related stress and burnout come home with them — 76% of respondents overall said that burnout had negatively affected their personal relationships.

Too many bureaucratic tasks such as charting and paperwork were by far the top contributor to burnout, reported by 70% of respondents, with insufficient compensation and lack of respect from employers, colleagues, and staff as relatively distant second and third contributors (40% and 37%, respectively).

In addition, nearly half of the physicians said that their burnout was severe enough that they might leave medicine. 

To help manage burnout, more internists reported positive coping strategies such as exercise (51%), talking with friends and family (47%), spending time alone (41%), and sleeping (40%), compared to less healthy strategies such as eating junk food, drinking alcohol, and using nicotine or cannabis products.

When asked what workplace measures would help with burnout, no one strategy rose to the top, but the top three were increased compensation (49%), additional support staff (48%), and more flexible work schedules (45%).

Notably, 62% of internists reported depression they defined as colloquial (feeling down or sad) and 27% described their depression as clinical. However, only 9% said they had sought professional help for depression, and 15% said they had sought help for burnout.
 

Staying in Practice Despite Burnout

The percentage of physicians across specialties who report depression and burnout worsened during the COVID-19 pandemic, said Noel Deep, MD, an internal medicine physician in group practice in Antigo, Wisconsin, in an interview.

Since the pandemic, newer stressors have replaced the pandemic-related stressors, and increasing bureaucratic burdens and paperwork continue to cause more physicians to report burnout, he said.

“If not assessed and addressed, this will lead to attrition in the physician workforce leading to increased burden on other physicians and impact patient access to healthcare,” he added.

The survey findings reflect Dr. Deep’s observations. “When talking to physicians across specialties, I have heard universally from many physicians about their experiences and ongoing struggles with potential burnout and mood-related issues,” he said. “While many of them feel that they are getting to the point of burnout, most of them also stoically continue to provide care to patients because they feel an obligation to them,” he said.

This feeling of obligation to patients is why less than one third of the physicians who consider retiring or leaving medicine because of burnout actually do, he said.

As for measures to reduce burnout, “I personally feel that increasing the compensation will not lead to decreased burnout,” Dr. Deep said. Although more money may provide temporary satisfaction, it will not yield long-term improvement in burnout, he said. “Based on personal experiences and my interactions with physicians, providing them more autonomy and control over their practices ... would contribute to decreasing the burnout,” Dr. Deep emphasized.
 

What Is to Be Done?

“I would favor having physician leaders in healthcare organizations take the time to talk to physicians [and] provide mentoring programs when new physicians are recruited, with ongoing discussions at operations and governance meetings about physician health and wellness,” Dr. Deep said. Providing frequent updates to physicians about wellness resources and encouraging them to seek out help anonymously through Employee Assistance Programs and other counseling services would be beneficial, he added.

“I would also consider peer mentoring when possible. Employers, healthcare organizations, and other key stakeholders should continue to work toward decreasing the stigma of depression and burnout,” Dr. Deep said.

Employers can help physicians manage and reduce burnout and depression by engaging with them, listening to their concerns, and trying to address them, said Dr. Deep. These actions will increase physicians’ trust in their administrations and promote a positive and healthy work environment, he said. “This will lead to reduced attrition in the workforce, retention of experienced physicians and support staff, and lead to increased patient satisfaction as well.”

The data come from Medscape’s annual report on Physician Burnout & Depression, which included 9226 practicing physicians in the United States across more than 29 specialties.

Dr. Deep had no financial conflicts to disclose; he serves on the Editorial Advisory Board of Internal Medicine News.

Reported burnout among internal medicine physicians decreased over the past year based on data from Medscape’s annual survey of burnout and depression among physicians in the United States.

Approximately 80% of male internists and 85% of female internists said that their feelings of burnout and/or depression were driven by their jobs all or most of the time. The job-related stress and burnout come home with them — 76% of respondents overall said that burnout had negatively affected their personal relationships.

Too many bureaucratic tasks such as charting and paperwork were by far the top contributor to burnout, reported by 70% of respondents, with insufficient compensation and lack of respect from employers, colleagues, and staff as relatively distant second and third contributors (40% and 37%, respectively).

In addition, nearly half of the physicians said that their burnout was severe enough that they might leave medicine. 

To help manage burnout, more internists reported positive coping strategies such as exercise (51%), talking with friends and family (47%), spending time alone (41%), and sleeping (40%), compared to less healthy strategies such as eating junk food, drinking alcohol, and using nicotine or cannabis products.

When asked what workplace measures would help with burnout, no one strategy rose to the top, but the top three were increased compensation (49%), additional support staff (48%), and more flexible work schedules (45%).

Notably, 62% of internists reported depression they defined as colloquial (feeling down or sad) and 27% described their depression as clinical. However, only 9% said they had sought professional help for depression, and 15% said they had sought help for burnout.
 

Staying in Practice Despite Burnout

The percentage of physicians across specialties who report depression and burnout worsened during the COVID-19 pandemic, said Noel Deep, MD, an internal medicine physician in group practice in Antigo, Wisconsin, in an interview.

Since the pandemic, newer stressors have replaced the pandemic-related stressors, and increasing bureaucratic burdens and paperwork continue to cause more physicians to report burnout, he said.

“If not assessed and addressed, this will lead to attrition in the physician workforce leading to increased burden on other physicians and impact patient access to healthcare,” he added.

The survey findings reflect Dr. Deep’s observations. “When talking to physicians across specialties, I have heard universally from many physicians about their experiences and ongoing struggles with potential burnout and mood-related issues,” he said. “While many of them feel that they are getting to the point of burnout, most of them also stoically continue to provide care to patients because they feel an obligation to them,” he said.

This feeling of obligation to patients is why less than one third of the physicians who consider retiring or leaving medicine because of burnout actually do, he said.

As for measures to reduce burnout, “I personally feel that increasing the compensation will not lead to decreased burnout,” Dr. Deep said. Although more money may provide temporary satisfaction, it will not yield long-term improvement in burnout, he said. “Based on personal experiences and my interactions with physicians, providing them more autonomy and control over their practices ... would contribute to decreasing the burnout,” Dr. Deep emphasized.
 

What Is to Be Done?

“I would favor having physician leaders in healthcare organizations take the time to talk to physicians [and] provide mentoring programs when new physicians are recruited, with ongoing discussions at operations and governance meetings about physician health and wellness,” Dr. Deep said. Providing frequent updates to physicians about wellness resources and encouraging them to seek out help anonymously through Employee Assistance Programs and other counseling services would be beneficial, he added.

“I would also consider peer mentoring when possible. Employers, healthcare organizations, and other key stakeholders should continue to work toward decreasing the stigma of depression and burnout,” Dr. Deep said.

Employers can help physicians manage and reduce burnout and depression by engaging with them, listening to their concerns, and trying to address them, said Dr. Deep. These actions will increase physicians’ trust in their administrations and promote a positive and healthy work environment, he said. “This will lead to reduced attrition in the workforce, retention of experienced physicians and support staff, and lead to increased patient satisfaction as well.”

The data come from Medscape’s annual report on Physician Burnout & Depression, which included 9226 practicing physicians in the United States across more than 29 specialties.

Dr. Deep had no financial conflicts to disclose; he serves on the Editorial Advisory Board of Internal Medicine News.

Reported burnout among internal medicine physicians decreased over the past year based on data from Medscape’s annual survey of burnout and depression among physicians in the United States.

Approximately 80% of male internists and 85% of female internists said that their feelings of burnout and/or depression were driven by their jobs all or most of the time. The job-related stress and burnout come home with them — 76% of respondents overall said that burnout had negatively affected their personal relationships.

Too many bureaucratic tasks such as charting and paperwork were by far the top contributor to burnout, reported by 70% of respondents, with insufficient compensation and lack of respect from employers, colleagues, and staff as relatively distant second and third contributors (40% and 37%, respectively).

In addition, nearly half of the physicians said that their burnout was severe enough that they might leave medicine. 

To help manage burnout, more internists reported positive coping strategies such as exercise (51%), talking with friends and family (47%), spending time alone (41%), and sleeping (40%), compared to less healthy strategies such as eating junk food, drinking alcohol, and using nicotine or cannabis products.

When asked what workplace measures would help with burnout, no one strategy rose to the top, but the top three were increased compensation (49%), additional support staff (48%), and more flexible work schedules (45%).

Notably, 62% of internists reported depression they defined as colloquial (feeling down or sad) and 27% described their depression as clinical. However, only 9% said they had sought professional help for depression, and 15% said they had sought help for burnout.
 

Staying in Practice Despite Burnout

The percentage of physicians across specialties who report depression and burnout worsened during the COVID-19 pandemic, said Noel Deep, MD, an internal medicine physician in group practice in Antigo, Wisconsin, in an interview.

Since the pandemic, newer stressors have replaced the pandemic-related stressors, and increasing bureaucratic burdens and paperwork continue to cause more physicians to report burnout, he said.

“If not assessed and addressed, this will lead to attrition in the physician workforce leading to increased burden on other physicians and impact patient access to healthcare,” he added.

The survey findings reflect Dr. Deep’s observations. “When talking to physicians across specialties, I have heard universally from many physicians about their experiences and ongoing struggles with potential burnout and mood-related issues,” he said. “While many of them feel that they are getting to the point of burnout, most of them also stoically continue to provide care to patients because they feel an obligation to them,” he said.

This feeling of obligation to patients is why less than one third of the physicians who consider retiring or leaving medicine because of burnout actually do, he said.

As for measures to reduce burnout, “I personally feel that increasing the compensation will not lead to decreased burnout,” Dr. Deep said. Although more money may provide temporary satisfaction, it will not yield long-term improvement in burnout, he said. “Based on personal experiences and my interactions with physicians, providing them more autonomy and control over their practices ... would contribute to decreasing the burnout,” Dr. Deep emphasized.
 

What Is to Be Done?

“I would favor having physician leaders in healthcare organizations take the time to talk to physicians [and] provide mentoring programs when new physicians are recruited, with ongoing discussions at operations and governance meetings about physician health and wellness,” Dr. Deep said. Providing frequent updates to physicians about wellness resources and encouraging them to seek out help anonymously through Employee Assistance Programs and other counseling services would be beneficial, he added.

“I would also consider peer mentoring when possible. Employers, healthcare organizations, and other key stakeholders should continue to work toward decreasing the stigma of depression and burnout,” Dr. Deep said.

Employers can help physicians manage and reduce burnout and depression by engaging with them, listening to their concerns, and trying to address them, said Dr. Deep. These actions will increase physicians’ trust in their administrations and promote a positive and healthy work environment, he said. “This will lead to reduced attrition in the workforce, retention of experienced physicians and support staff, and lead to increased patient satisfaction as well.”

The data come from Medscape’s annual report on Physician Burnout & Depression, which included 9226 practicing physicians in the United States across more than 29 specialties.

Dr. Deep had no financial conflicts to disclose; he serves on the Editorial Advisory Board of Internal Medicine News.

Reported burnout among family physicians was down slightly in 2023 from the previous year, but burnout lasted longer, based on data from this news organization’s annual survey of burnout and depression among physicians in the United States.

Overall, 70% of internists surveyed said they had felt burned out for at least 13 months, compared with 60% in the 2023 survey. Of these, 41% said they had experienced feelings of burnout out for more than 2 years.

Overall, 82% of both male and female family physicians who reported feeling burned out or depressed attributed their burnout or depression to job stress rather than stress in their personal lives.

Bureaucratic tasks such as charting and paperwork were cited by 73% of respondents as the greatest contributor to family physicians’ burnout, followed by too many hours at work (39%) and lack of respect from administrators, colleagues, or staff.

Notably, 45% responded with either a 4 or 5 on a 1-5 scale that their burnout was severe enough that they might consider leaving practice, and 73% of respondents said that burnout was taking a negative toll on their personal relationships, up from 67% in last year’s survey.

Depression also remains a problem for family physicians, but fewer than 20% reported seeking help for either depression or burnout (15% and 16%, respectively)

Among the 27% of respondents who reported clinical depression, 69% cited job burnout as a significant contributor.

The top three strategies cited by respondents to reduce burnout were more support staff, more flexible work schedules, and lighter patient loads.
 

Take Needs for Support Seriously

The findings reflect the need not only of increased administrative support, but also personal and emotional support to reduce burnout among family physicians, Susan K. Fidler, MD, associate director of the Family Medicine Residency Program at Jefferson Health, Abington, Pennsylvania, said in an interview.

“Family physicians are a critically important societal resource to support the health of communities,” she said.

“It takes at least 7 years to train a family physician, and we need to create a culture in medicine to keep these highly-trained specialists engaged in their work to continue to provide continuity of care to their communities,” said Dr. Fidler. “Losing a family physician to burnout directly impacts the care that community receives and further worsens someone’s ability to access care,” she said.

Dr. Fidler was not surprised by the impact of administrative work on a physicians’ experience of burnout. “Physicians are energized by taking care of patients, and it is hard to feel like you are helping people by wading through the paperwork and administrative burden associated with our healthcare system,” she said.

However, she was surprised by the higher burnout rate in female physicians compared with males (55% vs. 45%, respectively). “As the proportion of the family physician workforce becomes increasing female, it becomes critical to understand this difference and provide support to address their specific needs,” she said.

Dr. Fidler said she agreed with the reported top three measures that might reduce burnout among family physicians. “In order to take care of the complex needs of our patients, more support staff and more time with patients can increase satisfaction with the practice of medicine,” she added.

Currently, physicians are often choosing between staying on time in short appointment slots and taking the necessary time to address patients’ needs, said Dr. Fidler.

“Longer appointments and more support staff allow family physicians to use their excellent training to provide whole-person care,” she said.

Previous research has shown that helping family physicians identify the most meaningful aspects of their work can reduce burnout, Dr. Fidler said. “It is up to healthcare administrators to allow physicians the flexibility to find their meaning in work and to support the systems that allow physicians to practice efficiently and effectively,” she said.

The data come from Medscape’s annual report on Physician Burnout & Depression, which included 9226 practicing physicians in the United States across more than 29 specialties.

Dr. Fidler had no financial conflicts to disclose.

Reported burnout among family physicians was down slightly in 2023 from the previous year, but burnout lasted longer, based on data from this news organization’s annual survey of burnout and depression among physicians in the United States.

Overall, 70% of internists surveyed said they had felt burned out for at least 13 months, compared with 60% in the 2023 survey. Of these, 41% said they had experienced feelings of burnout out for more than 2 years.

Overall, 82% of both male and female family physicians who reported feeling burned out or depressed attributed their burnout or depression to job stress rather than stress in their personal lives.

Bureaucratic tasks such as charting and paperwork were cited by 73% of respondents as the greatest contributor to family physicians’ burnout, followed by too many hours at work (39%) and lack of respect from administrators, colleagues, or staff.

Notably, 45% responded with either a 4 or 5 on a 1-5 scale that their burnout was severe enough that they might consider leaving practice, and 73% of respondents said that burnout was taking a negative toll on their personal relationships, up from 67% in last year’s survey.

Depression also remains a problem for family physicians, but fewer than 20% reported seeking help for either depression or burnout (15% and 16%, respectively)

Among the 27% of respondents who reported clinical depression, 69% cited job burnout as a significant contributor.

The top three strategies cited by respondents to reduce burnout were more support staff, more flexible work schedules, and lighter patient loads.
 

Take Needs for Support Seriously

The findings reflect the need not only of increased administrative support, but also personal and emotional support to reduce burnout among family physicians, Susan K. Fidler, MD, associate director of the Family Medicine Residency Program at Jefferson Health, Abington, Pennsylvania, said in an interview.

“Family physicians are a critically important societal resource to support the health of communities,” she said.

“It takes at least 7 years to train a family physician, and we need to create a culture in medicine to keep these highly-trained specialists engaged in their work to continue to provide continuity of care to their communities,” said Dr. Fidler. “Losing a family physician to burnout directly impacts the care that community receives and further worsens someone’s ability to access care,” she said.

Dr. Fidler was not surprised by the impact of administrative work on a physicians’ experience of burnout. “Physicians are energized by taking care of patients, and it is hard to feel like you are helping people by wading through the paperwork and administrative burden associated with our healthcare system,” she said.

However, she was surprised by the higher burnout rate in female physicians compared with males (55% vs. 45%, respectively). “As the proportion of the family physician workforce becomes increasing female, it becomes critical to understand this difference and provide support to address their specific needs,” she said.

Dr. Fidler said she agreed with the reported top three measures that might reduce burnout among family physicians. “In order to take care of the complex needs of our patients, more support staff and more time with patients can increase satisfaction with the practice of medicine,” she added.

Currently, physicians are often choosing between staying on time in short appointment slots and taking the necessary time to address patients’ needs, said Dr. Fidler.

“Longer appointments and more support staff allow family physicians to use their excellent training to provide whole-person care,” she said.

Previous research has shown that helping family physicians identify the most meaningful aspects of their work can reduce burnout, Dr. Fidler said. “It is up to healthcare administrators to allow physicians the flexibility to find their meaning in work and to support the systems that allow physicians to practice efficiently and effectively,” she said.

The data come from Medscape’s annual report on Physician Burnout & Depression, which included 9226 practicing physicians in the United States across more than 29 specialties.

Dr. Fidler had no financial conflicts to disclose.

Reported burnout among family physicians was down slightly in 2023 from the previous year, but burnout lasted longer, based on data from this news organization’s annual survey of burnout and depression among physicians in the United States.

Overall, 70% of internists surveyed said they had felt burned out for at least 13 months, compared with 60% in the 2023 survey. Of these, 41% said they had experienced feelings of burnout out for more than 2 years.

Overall, 82% of both male and female family physicians who reported feeling burned out or depressed attributed their burnout or depression to job stress rather than stress in their personal lives.

Bureaucratic tasks such as charting and paperwork were cited by 73% of respondents as the greatest contributor to family physicians’ burnout, followed by too many hours at work (39%) and lack of respect from administrators, colleagues, or staff.

Notably, 45% responded with either a 4 or 5 on a 1-5 scale that their burnout was severe enough that they might consider leaving practice, and 73% of respondents said that burnout was taking a negative toll on their personal relationships, up from 67% in last year’s survey.

Depression also remains a problem for family physicians, but fewer than 20% reported seeking help for either depression or burnout (15% and 16%, respectively)

Among the 27% of respondents who reported clinical depression, 69% cited job burnout as a significant contributor.

The top three strategies cited by respondents to reduce burnout were more support staff, more flexible work schedules, and lighter patient loads.
 

Take Needs for Support Seriously

The findings reflect the need not only of increased administrative support, but also personal and emotional support to reduce burnout among family physicians, Susan K. Fidler, MD, associate director of the Family Medicine Residency Program at Jefferson Health, Abington, Pennsylvania, said in an interview.

“Family physicians are a critically important societal resource to support the health of communities,” she said.

“It takes at least 7 years to train a family physician, and we need to create a culture in medicine to keep these highly-trained specialists engaged in their work to continue to provide continuity of care to their communities,” said Dr. Fidler. “Losing a family physician to burnout directly impacts the care that community receives and further worsens someone’s ability to access care,” she said.

Dr. Fidler was not surprised by the impact of administrative work on a physicians’ experience of burnout. “Physicians are energized by taking care of patients, and it is hard to feel like you are helping people by wading through the paperwork and administrative burden associated with our healthcare system,” she said.

However, she was surprised by the higher burnout rate in female physicians compared with males (55% vs. 45%, respectively). “As the proportion of the family physician workforce becomes increasing female, it becomes critical to understand this difference and provide support to address their specific needs,” she said.

Dr. Fidler said she agreed with the reported top three measures that might reduce burnout among family physicians. “In order to take care of the complex needs of our patients, more support staff and more time with patients can increase satisfaction with the practice of medicine,” she added.

Currently, physicians are often choosing between staying on time in short appointment slots and taking the necessary time to address patients’ needs, said Dr. Fidler.

“Longer appointments and more support staff allow family physicians to use their excellent training to provide whole-person care,” she said.

Previous research has shown that helping family physicians identify the most meaningful aspects of their work can reduce burnout, Dr. Fidler said. “It is up to healthcare administrators to allow physicians the flexibility to find their meaning in work and to support the systems that allow physicians to practice efficiently and effectively,” she said.

The data come from Medscape’s annual report on Physician Burnout & Depression, which included 9226 practicing physicians in the United States across more than 29 specialties.

Dr. Fidler had no financial conflicts to disclose.

The advent of new immune checkpoint inhibitor combinations for urothelial carcinoma has yielded dramatic changes in patient care, according to Thomas W. Flaig, MD, vice chancellor for research at the University of Colorado Anschutz Medical Campus, Aurora.

Combination therapies involving enfortumab and nivolumab are demonstrating success in recent studies and have been incorporated into the latest guidelines, Dr. Flaig said in a presentation at the National Comprehensive Cancer Network (NCCN) annual conference.
 

What's New in The Updated Guidelines?

Advances in the treatment options for metastatic urothelial carcinoma in the last decade have been dramatic, with ongoing developments and new emerging treatment options, Dr. Flaig told the audience of his session.

This has led to the identification of new and effective immune checkpoint inhibitor combinations. Consequently, immune checkpoint inhibitors are currently included in all preferred/other recommended first-line treatment regimens, he said.

“Enfortumab vedotin plus pembrolizumab is now the sole preferred first-line regimen for locally advanced or metastatic disease.” Based on the recent research, the mindset regarding cisplatin-eligible patient selection may be changing, he added.

“We have used cisplatin eligibility as a key factor in determining first-line therapy for years, and that paradigm is now shifting with the emergence of enfortumab plus pembrolizumab, a new non–cisplatin containing regimen” Dr. Flaig noted.

Although the optimal choice for second- or third-line therapy after immune checkpoint inhibitors is not well-defined, options include platinum regimens, antibody-drug conjugate, and erdafitinib in eligible patients, he said.
 

Other Current Strategies for Localized Bladder Cancer Management

The incidence of bladder cancer has been stable for decades, with minimal therapeutic developments until the approval of immune checkpoint inhibitors in the last decade, Dr. Flaig said.

Bladder cancer is more common in older adults, with an average onset age of 73 years, and most patients (75%) are male, he said. Comorbid disease is common in these patients, and many have a history of smoking, Dr. Flaig added.

The traditional medical approach to treating bladder cancer has been based on combination therapies including cisplatin. This has also reflected the approach used in the treatment of lung cancer, historically, Dr. Flaig said.

Cisplatin, while effective, is a challenging therapy to administer and is not an option for all bladder cancer patients because of potential adverse effects, he noted. Antibody drug conjugates and immune checkpoint inhibitors are new alternatives for some who are not able to receive cisplatin.

What are the New Options for Treating Metastatic Urothelial Bladder Cancer?

The approval of antibody drug conjugates offers new treatment with a “specific target and therapeutic payload,” said Dr. Flaig in his presentation. Two antibody drug conjugates, enfortumab vedotin and sacituzumab govitecan, have been approved by the US Food and Drug Administration (FDA), he said. Enforumab vedotin was approved by the FDA in 2021 for adults with locally advanced or metastatic urothelial cancer for subsequent line therapy in select patients. In a 2021 study published in The New England Journal of Medicine, the primary outcome of overall response rate was significantly greater in patients with advanced urothelial carcinoma who were treated with enfortumab vedotin than in those treated with standard chemotherapy (overall response rate [ORR] 40.6% vs 17.9%, respectively).

Side effects associated with enfortumab vedotin “are intrinsic to the payload toxicity and the target distribution. Ideally, the target would be present on all of the cancer cells and none of the normal tissue,” said Dr. Flaig. With enfortumab, specific toxicities included neuropathy, skin reactions, and blood glucose elevation/diabetic ketoacidosis, he said.

A second agent, sacituzumab govitecan, was approved by the FDA for metastatic urothelial cancer patients in 2021, based on data from the TROPHY-U-O1 phase 2 open-label study of 113 individuals. In that study, the ORR was 27% at a median follow-up of 9.1 months. Adverse events included neutropenia, leukopenia, and diarrhea.
 

What Do the Latest Studies of Combination Therapy Show?

Immune checkpoint inhibitor combinations are significantly changing the landscape of bladder cancer treatment, Dr. Flaig explained.

A recent phase 3 study published in 2024 in The New England Journal of Medicine comparing enfortumab vedotin plus pembrolizumab to platinum-based combination chemotherapy showed an overall response rate of 67.7% vs 44.4% in favor of enfortumab/pembrolizumab, said Dr. Flaig. In addition, the risk of disease progression or death was approximately 55% lower in the enfortumab vedotin-pembrolizumab group vs the chemotherapy group (hazard ratio [HR], 0.45; P less than .001) and the median progression-free survival was approximately doubled (12.5 months vs 6.3 months).

Dr. Flaig described this study as “very notable”because “the enfortumab plus pembrolizumab arm was clearly more effective than the long-standing chemotherapy arm, now becoming the preferred, first-line treatment in the NCCN guidelines. Based on preliminary results of the study, this combination was approved by the FDA in 2023 for locally advanced or metastatic urothelial cancer patients regardless of their eligibility for cisplatin.

Another promising combination, nivolumab plus gemcitabine-cisplatin, was associated with significantly longer overall and progression-free survival in patients with previously untreated unresectable or metastatic urothelial carcinoma, Dr. Flaig said. The therapy was approved by the FDA in March 2024 for first-line therapy.

In a study of 608 patients published in The New England Journal of Medicine, median overall survival was 21.7 months for the nivolumab group vs 18.9 months for the gemcitabine-cisplatin alone group. The overall response rates were 57.6% in the nivolumab group vs 43.1% in the gemcitabine-cisplatin–alone group, and complete response rates were 21.7% and 11.8%, respectively. Serious adverse events (grade 3 or higher) were similar between the groups (61.8% and 51.7%, respectively).
 

What About Targeted Therapy?

Erdafitinib, a tyrosine kinase inhibitor of FGFR1–4, was approved by the FDA in January 2024 for adults with locally advanced or metastatic urothelial carcinoma who had susceptible FGFR3 genetic alterations, said Dr. Flaig, during his presentation. The limitation of this treatment to only those patients with an FGFR3 mutation is a recent update in its use, he noted.

“Up to 20% of patients with advanced urothelial carcinoma have FGFR alterations,” he said. In an open-label phase 2 study of 99 individuals with unresectable or metastatic urothelial carcinoma, past chemotherapy, and FGFR alterations, confirmed response to erdafitinib was 40% with a median overall survival of 13.8 months.

Dr. Flaig disclosed grant/research support from Agensys; Astellas Pharma US; AstraZeneca Pharmaceuticals LP; Bristol Myers Squibb; Genentech, Inc.; Janssen Pharmaceutica Products, LP; Merck & Co.; Sanofi-Aventis U.S.; and SeaGen. He also disclosed equity interest/stock options and intellectual property rights in Aurora Oncology, and serving as a consultant or scientific advisor for Janssen Pharmaceutica Product, LP, and Criterium, Inc.

The advent of new immune checkpoint inhibitor combinations for urothelial carcinoma has yielded dramatic changes in patient care, according to Thomas W. Flaig, MD, vice chancellor for research at the University of Colorado Anschutz Medical Campus, Aurora.

Combination therapies involving enfortumab and nivolumab are demonstrating success in recent studies and have been incorporated into the latest guidelines, Dr. Flaig said in a presentation at the National Comprehensive Cancer Network (NCCN) annual conference.
 

What's New in The Updated Guidelines?

Advances in the treatment options for metastatic urothelial carcinoma in the last decade have been dramatic, with ongoing developments and new emerging treatment options, Dr. Flaig told the audience of his session.

This has led to the identification of new and effective immune checkpoint inhibitor combinations. Consequently, immune checkpoint inhibitors are currently included in all preferred/other recommended first-line treatment regimens, he said.

“Enfortumab vedotin plus pembrolizumab is now the sole preferred first-line regimen for locally advanced or metastatic disease.” Based on the recent research, the mindset regarding cisplatin-eligible patient selection may be changing, he added.

“We have used cisplatin eligibility as a key factor in determining first-line therapy for years, and that paradigm is now shifting with the emergence of enfortumab plus pembrolizumab, a new non–cisplatin containing regimen” Dr. Flaig noted.

Although the optimal choice for second- or third-line therapy after immune checkpoint inhibitors is not well-defined, options include platinum regimens, antibody-drug conjugate, and erdafitinib in eligible patients, he said.
 

Other Current Strategies for Localized Bladder Cancer Management

The incidence of bladder cancer has been stable for decades, with minimal therapeutic developments until the approval of immune checkpoint inhibitors in the last decade, Dr. Flaig said.

Bladder cancer is more common in older adults, with an average onset age of 73 years, and most patients (75%) are male, he said. Comorbid disease is common in these patients, and many have a history of smoking, Dr. Flaig added.

The traditional medical approach to treating bladder cancer has been based on combination therapies including cisplatin. This has also reflected the approach used in the treatment of lung cancer, historically, Dr. Flaig said.

Cisplatin, while effective, is a challenging therapy to administer and is not an option for all bladder cancer patients because of potential adverse effects, he noted. Antibody drug conjugates and immune checkpoint inhibitors are new alternatives for some who are not able to receive cisplatin.

What are the New Options for Treating Metastatic Urothelial Bladder Cancer?

The approval of antibody drug conjugates offers new treatment with a “specific target and therapeutic payload,” said Dr. Flaig in his presentation. Two antibody drug conjugates, enfortumab vedotin and sacituzumab govitecan, have been approved by the US Food and Drug Administration (FDA), he said. Enforumab vedotin was approved by the FDA in 2021 for adults with locally advanced or metastatic urothelial cancer for subsequent line therapy in select patients. In a 2021 study published in The New England Journal of Medicine, the primary outcome of overall response rate was significantly greater in patients with advanced urothelial carcinoma who were treated with enfortumab vedotin than in those treated with standard chemotherapy (overall response rate [ORR] 40.6% vs 17.9%, respectively).

Side effects associated with enfortumab vedotin “are intrinsic to the payload toxicity and the target distribution. Ideally, the target would be present on all of the cancer cells and none of the normal tissue,” said Dr. Flaig. With enfortumab, specific toxicities included neuropathy, skin reactions, and blood glucose elevation/diabetic ketoacidosis, he said.

A second agent, sacituzumab govitecan, was approved by the FDA for metastatic urothelial cancer patients in 2021, based on data from the TROPHY-U-O1 phase 2 open-label study of 113 individuals. In that study, the ORR was 27% at a median follow-up of 9.1 months. Adverse events included neutropenia, leukopenia, and diarrhea.
 

What Do the Latest Studies of Combination Therapy Show?

Immune checkpoint inhibitor combinations are significantly changing the landscape of bladder cancer treatment, Dr. Flaig explained.

A recent phase 3 study published in 2024 in The New England Journal of Medicine comparing enfortumab vedotin plus pembrolizumab to platinum-based combination chemotherapy showed an overall response rate of 67.7% vs 44.4% in favor of enfortumab/pembrolizumab, said Dr. Flaig. In addition, the risk of disease progression or death was approximately 55% lower in the enfortumab vedotin-pembrolizumab group vs the chemotherapy group (hazard ratio [HR], 0.45; P less than .001) and the median progression-free survival was approximately doubled (12.5 months vs 6.3 months).

Dr. Flaig described this study as “very notable”because “the enfortumab plus pembrolizumab arm was clearly more effective than the long-standing chemotherapy arm, now becoming the preferred, first-line treatment in the NCCN guidelines. Based on preliminary results of the study, this combination was approved by the FDA in 2023 for locally advanced or metastatic urothelial cancer patients regardless of their eligibility for cisplatin.

Another promising combination, nivolumab plus gemcitabine-cisplatin, was associated with significantly longer overall and progression-free survival in patients with previously untreated unresectable or metastatic urothelial carcinoma, Dr. Flaig said. The therapy was approved by the FDA in March 2024 for first-line therapy.

In a study of 608 patients published in The New England Journal of Medicine, median overall survival was 21.7 months for the nivolumab group vs 18.9 months for the gemcitabine-cisplatin alone group. The overall response rates were 57.6% in the nivolumab group vs 43.1% in the gemcitabine-cisplatin–alone group, and complete response rates were 21.7% and 11.8%, respectively. Serious adverse events (grade 3 or higher) were similar between the groups (61.8% and 51.7%, respectively).
 

What About Targeted Therapy?

Erdafitinib, a tyrosine kinase inhibitor of FGFR1–4, was approved by the FDA in January 2024 for adults with locally advanced or metastatic urothelial carcinoma who had susceptible FGFR3 genetic alterations, said Dr. Flaig, during his presentation. The limitation of this treatment to only those patients with an FGFR3 mutation is a recent update in its use, he noted.

“Up to 20% of patients with advanced urothelial carcinoma have FGFR alterations,” he said. In an open-label phase 2 study of 99 individuals with unresectable or metastatic urothelial carcinoma, past chemotherapy, and FGFR alterations, confirmed response to erdafitinib was 40% with a median overall survival of 13.8 months.

Dr. Flaig disclosed grant/research support from Agensys; Astellas Pharma US; AstraZeneca Pharmaceuticals LP; Bristol Myers Squibb; Genentech, Inc.; Janssen Pharmaceutica Products, LP; Merck & Co.; Sanofi-Aventis U.S.; and SeaGen. He also disclosed equity interest/stock options and intellectual property rights in Aurora Oncology, and serving as a consultant or scientific advisor for Janssen Pharmaceutica Product, LP, and Criterium, Inc.

The advent of new immune checkpoint inhibitor combinations for urothelial carcinoma has yielded dramatic changes in patient care, according to Thomas W. Flaig, MD, vice chancellor for research at the University of Colorado Anschutz Medical Campus, Aurora.

Combination therapies involving enfortumab and nivolumab are demonstrating success in recent studies and have been incorporated into the latest guidelines, Dr. Flaig said in a presentation at the National Comprehensive Cancer Network (NCCN) annual conference.
 

What's New in The Updated Guidelines?

Advances in the treatment options for metastatic urothelial carcinoma in the last decade have been dramatic, with ongoing developments and new emerging treatment options, Dr. Flaig told the audience of his session.

This has led to the identification of new and effective immune checkpoint inhibitor combinations. Consequently, immune checkpoint inhibitors are currently included in all preferred/other recommended first-line treatment regimens, he said.

“Enfortumab vedotin plus pembrolizumab is now the sole preferred first-line regimen for locally advanced or metastatic disease.” Based on the recent research, the mindset regarding cisplatin-eligible patient selection may be changing, he added.

“We have used cisplatin eligibility as a key factor in determining first-line therapy for years, and that paradigm is now shifting with the emergence of enfortumab plus pembrolizumab, a new non–cisplatin containing regimen” Dr. Flaig noted.

Although the optimal choice for second- or third-line therapy after immune checkpoint inhibitors is not well-defined, options include platinum regimens, antibody-drug conjugate, and erdafitinib in eligible patients, he said.
 

Other Current Strategies for Localized Bladder Cancer Management

The incidence of bladder cancer has been stable for decades, with minimal therapeutic developments until the approval of immune checkpoint inhibitors in the last decade, Dr. Flaig said.

Bladder cancer is more common in older adults, with an average onset age of 73 years, and most patients (75%) are male, he said. Comorbid disease is common in these patients, and many have a history of smoking, Dr. Flaig added.

The traditional medical approach to treating bladder cancer has been based on combination therapies including cisplatin. This has also reflected the approach used in the treatment of lung cancer, historically, Dr. Flaig said.

Cisplatin, while effective, is a challenging therapy to administer and is not an option for all bladder cancer patients because of potential adverse effects, he noted. Antibody drug conjugates and immune checkpoint inhibitors are new alternatives for some who are not able to receive cisplatin.

What are the New Options for Treating Metastatic Urothelial Bladder Cancer?

The approval of antibody drug conjugates offers new treatment with a “specific target and therapeutic payload,” said Dr. Flaig in his presentation. Two antibody drug conjugates, enfortumab vedotin and sacituzumab govitecan, have been approved by the US Food and Drug Administration (FDA), he said. Enforumab vedotin was approved by the FDA in 2021 for adults with locally advanced or metastatic urothelial cancer for subsequent line therapy in select patients. In a 2021 study published in The New England Journal of Medicine, the primary outcome of overall response rate was significantly greater in patients with advanced urothelial carcinoma who were treated with enfortumab vedotin than in those treated with standard chemotherapy (overall response rate [ORR] 40.6% vs 17.9%, respectively).

Side effects associated with enfortumab vedotin “are intrinsic to the payload toxicity and the target distribution. Ideally, the target would be present on all of the cancer cells and none of the normal tissue,” said Dr. Flaig. With enfortumab, specific toxicities included neuropathy, skin reactions, and blood glucose elevation/diabetic ketoacidosis, he said.

A second agent, sacituzumab govitecan, was approved by the FDA for metastatic urothelial cancer patients in 2021, based on data from the TROPHY-U-O1 phase 2 open-label study of 113 individuals. In that study, the ORR was 27% at a median follow-up of 9.1 months. Adverse events included neutropenia, leukopenia, and diarrhea.
 

What Do the Latest Studies of Combination Therapy Show?

Immune checkpoint inhibitor combinations are significantly changing the landscape of bladder cancer treatment, Dr. Flaig explained.

A recent phase 3 study published in 2024 in The New England Journal of Medicine comparing enfortumab vedotin plus pembrolizumab to platinum-based combination chemotherapy showed an overall response rate of 67.7% vs 44.4% in favor of enfortumab/pembrolizumab, said Dr. Flaig. In addition, the risk of disease progression or death was approximately 55% lower in the enfortumab vedotin-pembrolizumab group vs the chemotherapy group (hazard ratio [HR], 0.45; P less than .001) and the median progression-free survival was approximately doubled (12.5 months vs 6.3 months).

Dr. Flaig described this study as “very notable”because “the enfortumab plus pembrolizumab arm was clearly more effective than the long-standing chemotherapy arm, now becoming the preferred, first-line treatment in the NCCN guidelines. Based on preliminary results of the study, this combination was approved by the FDA in 2023 for locally advanced or metastatic urothelial cancer patients regardless of their eligibility for cisplatin.

Another promising combination, nivolumab plus gemcitabine-cisplatin, was associated with significantly longer overall and progression-free survival in patients with previously untreated unresectable or metastatic urothelial carcinoma, Dr. Flaig said. The therapy was approved by the FDA in March 2024 for first-line therapy.

In a study of 608 patients published in The New England Journal of Medicine, median overall survival was 21.7 months for the nivolumab group vs 18.9 months for the gemcitabine-cisplatin alone group. The overall response rates were 57.6% in the nivolumab group vs 43.1% in the gemcitabine-cisplatin–alone group, and complete response rates were 21.7% and 11.8%, respectively. Serious adverse events (grade 3 or higher) were similar between the groups (61.8% and 51.7%, respectively).
 

What About Targeted Therapy?

Erdafitinib, a tyrosine kinase inhibitor of FGFR1–4, was approved by the FDA in January 2024 for adults with locally advanced or metastatic urothelial carcinoma who had susceptible FGFR3 genetic alterations, said Dr. Flaig, during his presentation. The limitation of this treatment to only those patients with an FGFR3 mutation is a recent update in its use, he noted.

“Up to 20% of patients with advanced urothelial carcinoma have FGFR alterations,” he said. In an open-label phase 2 study of 99 individuals with unresectable or metastatic urothelial carcinoma, past chemotherapy, and FGFR alterations, confirmed response to erdafitinib was 40% with a median overall survival of 13.8 months.

Dr. Flaig disclosed grant/research support from Agensys; Astellas Pharma US; AstraZeneca Pharmaceuticals LP; Bristol Myers Squibb; Genentech, Inc.; Janssen Pharmaceutica Products, LP; Merck & Co.; Sanofi-Aventis U.S.; and SeaGen. He also disclosed equity interest/stock options and intellectual property rights in Aurora Oncology, and serving as a consultant or scientific advisor for Janssen Pharmaceutica Product, LP, and Criterium, Inc.