Colon and Rectal

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.

Last year, I concluded a commentary for this news organization on colorectal cancer (CRC) screening guidelines by stating that between stool-based tests, flexible sigmoidoscopy, and colonoscopy, “the best screening test is the test that gets done.” But should that maxim apply to the new blood-based screening test, Guardant Health Shield? This proprietary test, which costs $895 and is not generally covered by insurance, identifies alterations in cell-free DNA that are characteristic of CRC.

Shield’s test characteristics were recently evaluated in a prospective study of more than 10,000 adults aged 45-84 at average risk for CRC. The test had an 87.5% sensitivity for stage I, II, or III colorectal cancer but only a 13% sensitivity for advanced precancerous lesions. Test specificity was 89.6%, meaning that about 1 in 10 participants without CRC or advanced precancerous lesions on colonoscopy had a false-positive result.

Although the Shield blood test has a higher rate of false positives than the traditional fecal immunochemical test (FIT) and lower sensitivity and specificity than a multitarget stool DNA (FIT-DNA) test designed to improve on Cologuard, it meets the previously established criteria set forth by the Centers for Medicare & Medicaid Services (CMS) to be covered for Medicare beneficiaries at 3-year intervals, pending FDA approval. If public and private payers start covering Shield alongside other CRC screening tests, it presents an opportunity for primary care physicians to reach the approximately 3 in 10 adults between ages 45 and 75 who are not being routinely screened.

A big concern, however, is that the availability of a blood test may cause patients who would have otherwise been screened with colonoscopy or stool tests to switch to the blood test. A cost-effectiveness analysis found that offering a blood test to patients who decline screening colonoscopy saves additional lives, but at the cost of more than $377,000 per life-year gained. Another study relying on three microsimulation models previously utilized by the US Preventive Services Task Force (USPSTF) found that annual FIT results in more life-years gained at substantially lower cost than blood-based screening every 3 years “even when uptake of blood-based screening was 20 percentage points higher than uptake of FIT.” As a result, a multidisciplinary expert panel concluded that blood-based screening should not substitute for established CRC screening tests, but instead be offered only to patients who decline those tests.

In practice, this will increase the complexity of the CRC screening conversations we have with patients. We will need to be clear that the blood test is not yet endorsed by the USPSTF or any major guideline group and is a second-line test that will miss most precancerous polyps. As with the stool tests, it is essential to emphasize that a positive result must be followed by diagnostic colonoscopy. To addend the cancer screening maxim I mentioned before, the blood test is not the best test for CRC, but it’s probably better than no test at all.

Dr. Lin is a family physician and associate director, Family Medicine Residency Program, Lancaster General Hospital, Lancaster, Pennsylvania. He blogs at Common Sense Family Doctor.

A version of this article appeared on Medscape.com.

Last year, I concluded a commentary for this news organization on colorectal cancer (CRC) screening guidelines by stating that between stool-based tests, flexible sigmoidoscopy, and colonoscopy, “the best screening test is the test that gets done.” But should that maxim apply to the new blood-based screening test, Guardant Health Shield? This proprietary test, which costs $895 and is not generally covered by insurance, identifies alterations in cell-free DNA that are characteristic of CRC.

Shield’s test characteristics were recently evaluated in a prospective study of more than 10,000 adults aged 45-84 at average risk for CRC. The test had an 87.5% sensitivity for stage I, II, or III colorectal cancer but only a 13% sensitivity for advanced precancerous lesions. Test specificity was 89.6%, meaning that about 1 in 10 participants without CRC or advanced precancerous lesions on colonoscopy had a false-positive result.

Although the Shield blood test has a higher rate of false positives than the traditional fecal immunochemical test (FIT) and lower sensitivity and specificity than a multitarget stool DNA (FIT-DNA) test designed to improve on Cologuard, it meets the previously established criteria set forth by the Centers for Medicare & Medicaid Services (CMS) to be covered for Medicare beneficiaries at 3-year intervals, pending FDA approval. If public and private payers start covering Shield alongside other CRC screening tests, it presents an opportunity for primary care physicians to reach the approximately 3 in 10 adults between ages 45 and 75 who are not being routinely screened.

A big concern, however, is that the availability of a blood test may cause patients who would have otherwise been screened with colonoscopy or stool tests to switch to the blood test. A cost-effectiveness analysis found that offering a blood test to patients who decline screening colonoscopy saves additional lives, but at the cost of more than $377,000 per life-year gained. Another study relying on three microsimulation models previously utilized by the US Preventive Services Task Force (USPSTF) found that annual FIT results in more life-years gained at substantially lower cost than blood-based screening every 3 years “even when uptake of blood-based screening was 20 percentage points higher than uptake of FIT.” As a result, a multidisciplinary expert panel concluded that blood-based screening should not substitute for established CRC screening tests, but instead be offered only to patients who decline those tests.

In practice, this will increase the complexity of the CRC screening conversations we have with patients. We will need to be clear that the blood test is not yet endorsed by the USPSTF or any major guideline group and is a second-line test that will miss most precancerous polyps. As with the stool tests, it is essential to emphasize that a positive result must be followed by diagnostic colonoscopy. To addend the cancer screening maxim I mentioned before, the blood test is not the best test for CRC, but it’s probably better than no test at all.

Dr. Lin is a family physician and associate director, Family Medicine Residency Program, Lancaster General Hospital, Lancaster, Pennsylvania. He blogs at Common Sense Family Doctor.

A version of this article appeared on Medscape.com.

Last year, I concluded a commentary for this news organization on colorectal cancer (CRC) screening guidelines by stating that between stool-based tests, flexible sigmoidoscopy, and colonoscopy, “the best screening test is the test that gets done.” But should that maxim apply to the new blood-based screening test, Guardant Health Shield? This proprietary test, which costs $895 and is not generally covered by insurance, identifies alterations in cell-free DNA that are characteristic of CRC.

Shield’s test characteristics were recently evaluated in a prospective study of more than 10,000 adults aged 45-84 at average risk for CRC. The test had an 87.5% sensitivity for stage I, II, or III colorectal cancer but only a 13% sensitivity for advanced precancerous lesions. Test specificity was 89.6%, meaning that about 1 in 10 participants without CRC or advanced precancerous lesions on colonoscopy had a false-positive result.

Although the Shield blood test has a higher rate of false positives than the traditional fecal immunochemical test (FIT) and lower sensitivity and specificity than a multitarget stool DNA (FIT-DNA) test designed to improve on Cologuard, it meets the previously established criteria set forth by the Centers for Medicare & Medicaid Services (CMS) to be covered for Medicare beneficiaries at 3-year intervals, pending FDA approval. If public and private payers start covering Shield alongside other CRC screening tests, it presents an opportunity for primary care physicians to reach the approximately 3 in 10 adults between ages 45 and 75 who are not being routinely screened.

A big concern, however, is that the availability of a blood test may cause patients who would have otherwise been screened with colonoscopy or stool tests to switch to the blood test. A cost-effectiveness analysis found that offering a blood test to patients who decline screening colonoscopy saves additional lives, but at the cost of more than $377,000 per life-year gained. Another study relying on three microsimulation models previously utilized by the US Preventive Services Task Force (USPSTF) found that annual FIT results in more life-years gained at substantially lower cost than blood-based screening every 3 years “even when uptake of blood-based screening was 20 percentage points higher than uptake of FIT.” As a result, a multidisciplinary expert panel concluded that blood-based screening should not substitute for established CRC screening tests, but instead be offered only to patients who decline those tests.

In practice, this will increase the complexity of the CRC screening conversations we have with patients. We will need to be clear that the blood test is not yet endorsed by the USPSTF or any major guideline group and is a second-line test that will miss most precancerous polyps. As with the stool tests, it is essential to emphasize that a positive result must be followed by diagnostic colonoscopy. To addend the cancer screening maxim I mentioned before, the blood test is not the best test for CRC, but it’s probably better than no test at all.

Dr. Lin is a family physician and associate director, Family Medicine Residency Program, Lancaster General Hospital, Lancaster, Pennsylvania. He blogs at Common Sense Family Doctor.

A version of this article appeared on Medscape.com.

Gut microbiota signatures associated with KRAS mutations in patients with colorectal cancer (CRC) have been identified by researchers.

Their findings suggest that the gut microbes may serve as noninvasive biomarkers to help identify subtypes of CRC and guide personalized treatment recommendations.

“Our new work contributes to the growing body of evidence highlighting the significance of microbiota-driven mechanisms in cancer pathogenesis,” lead investigator Weizhong Tang, MD, with Guangxi Medical University Cancer Hospital in Nanning, China, said in a statement. 

The research was recently published online in Microbiology Spectrum. 

The onset and growth of CRC has been linked both to imbalances in the gut microbiome and to mutations in the KRAS gene — about 40% of people with CRC have a KRAS mutation. Yet, the interplay between gut dysbiosis and KRAS mutations in CRC remains unclear. 

To investigate further, Dr. Tang and colleagues used 16s rRNA sequencing to analyze stool samples from 94 patients with CRC, including 24 with KRAS-mutated CRC and 70 with KRAS wild-type (nonmutated) CRC. 

The researchers identified 26 distinct types of gut microbiota with statistically significant differences in abundance between the KRAS mutant and KRAS wild-type CRC patients.

At the genus level, Fusobacterium, Clostridium, and Shewanella were all abundant in the KRAS mutant group. 

Fusobacterium is a Gram-negative microbe found in the gastrointestinal tract and the oral cavity. Recent studies have established a strong link between Fusobacterium and CRC development. Other work found elevated levels of Fusobacterium nucleatum were not only closely associated with KRAS mutation but also correlated with chemoresistance in CRC.

Clostridium produces metabolites in the large intestine, which are known to cause DNA damage and trigger inflammatory responses, thereby increasing the risk of CRC development. 

Similarly, Shewanella has been proven to be a contributor to CRC development.

The researchers say it’s “plausible” to consider all three as potential noninvasive biomarkers for identifying KRAS mutation in CRC patients.

In contrast, Bifidobacterium and Akkermansia were abundant in the KRAS wild-type group. 

Bifidobacterium is a probiotic with antitumor activity and Akkermansia is a Gram-negative anaerobic bacterium abundant in the gut and currently recognized as a potential probiotic. 

The researchers speculated that CRC patients may have a reduced likelihood of developing KRAS mutation in the presence of Bifidobacterium and Akkermansia.

Analyses of biological pathways of gut microbiota associated with KRAS mutation status in CRC revealed a significantly higher abundance of the isoflavonoid biosynthesis pathway in the KRAS wild-type group compared with the KRAS mutant group.

“In comparison to KRAS mutant CRC, it is postulated that KRAS wild-type CRC may be less aggressive due to the upregulation of the isoflavonoid biosynthesis pathway, which may inhibit CRC development and progression,” the authors wrote.

Promising Predictive Model

Dr. Tang and colleagues also developed a machine learning model to predict KRAS mutation status in CRC patients based on the gut microbiota signature in KRAS mutant CRC. 

The initial results underscore the model’s predictive efficacy and suggest that it has “considerable potential for clinical application, offering a novel dimension in the prediction of KRAS mutation status among CRC patients in a clinical setting,” the authors wrote. 

They caution that the model requires data from a larger cohort to improve its efficacy, and they plan to do larger studies to validate the findings. 

The study had no commercial funding. The authors declared no relevant conflicts of interest. 

A version of this article appeared on Medscape.com.

Gut microbiota signatures associated with KRAS mutations in patients with colorectal cancer (CRC) have been identified by researchers.

Their findings suggest that the gut microbes may serve as noninvasive biomarkers to help identify subtypes of CRC and guide personalized treatment recommendations.

“Our new work contributes to the growing body of evidence highlighting the significance of microbiota-driven mechanisms in cancer pathogenesis,” lead investigator Weizhong Tang, MD, with Guangxi Medical University Cancer Hospital in Nanning, China, said in a statement. 

The research was recently published online in Microbiology Spectrum. 

The onset and growth of CRC has been linked both to imbalances in the gut microbiome and to mutations in the KRAS gene — about 40% of people with CRC have a KRAS mutation. Yet, the interplay between gut dysbiosis and KRAS mutations in CRC remains unclear. 

To investigate further, Dr. Tang and colleagues used 16s rRNA sequencing to analyze stool samples from 94 patients with CRC, including 24 with KRAS-mutated CRC and 70 with KRAS wild-type (nonmutated) CRC. 

The researchers identified 26 distinct types of gut microbiota with statistically significant differences in abundance between the KRAS mutant and KRAS wild-type CRC patients.

At the genus level, Fusobacterium, Clostridium, and Shewanella were all abundant in the KRAS mutant group. 

Fusobacterium is a Gram-negative microbe found in the gastrointestinal tract and the oral cavity. Recent studies have established a strong link between Fusobacterium and CRC development. Other work found elevated levels of Fusobacterium nucleatum were not only closely associated with KRAS mutation but also correlated with chemoresistance in CRC.

Clostridium produces metabolites in the large intestine, which are known to cause DNA damage and trigger inflammatory responses, thereby increasing the risk of CRC development. 

Similarly, Shewanella has been proven to be a contributor to CRC development.

The researchers say it’s “plausible” to consider all three as potential noninvasive biomarkers for identifying KRAS mutation in CRC patients.

In contrast, Bifidobacterium and Akkermansia were abundant in the KRAS wild-type group. 

Bifidobacterium is a probiotic with antitumor activity and Akkermansia is a Gram-negative anaerobic bacterium abundant in the gut and currently recognized as a potential probiotic. 

The researchers speculated that CRC patients may have a reduced likelihood of developing KRAS mutation in the presence of Bifidobacterium and Akkermansia.

Analyses of biological pathways of gut microbiota associated with KRAS mutation status in CRC revealed a significantly higher abundance of the isoflavonoid biosynthesis pathway in the KRAS wild-type group compared with the KRAS mutant group.

“In comparison to KRAS mutant CRC, it is postulated that KRAS wild-type CRC may be less aggressive due to the upregulation of the isoflavonoid biosynthesis pathway, which may inhibit CRC development and progression,” the authors wrote.

Promising Predictive Model

Dr. Tang and colleagues also developed a machine learning model to predict KRAS mutation status in CRC patients based on the gut microbiota signature in KRAS mutant CRC. 

The initial results underscore the model’s predictive efficacy and suggest that it has “considerable potential for clinical application, offering a novel dimension in the prediction of KRAS mutation status among CRC patients in a clinical setting,” the authors wrote. 

They caution that the model requires data from a larger cohort to improve its efficacy, and they plan to do larger studies to validate the findings. 

The study had no commercial funding. The authors declared no relevant conflicts of interest. 

A version of this article appeared on Medscape.com.

Gut microbiota signatures associated with KRAS mutations in patients with colorectal cancer (CRC) have been identified by researchers.

Their findings suggest that the gut microbes may serve as noninvasive biomarkers to help identify subtypes of CRC and guide personalized treatment recommendations.

“Our new work contributes to the growing body of evidence highlighting the significance of microbiota-driven mechanisms in cancer pathogenesis,” lead investigator Weizhong Tang, MD, with Guangxi Medical University Cancer Hospital in Nanning, China, said in a statement. 

The research was recently published online in Microbiology Spectrum. 

The onset and growth of CRC has been linked both to imbalances in the gut microbiome and to mutations in the KRAS gene — about 40% of people with CRC have a KRAS mutation. Yet, the interplay between gut dysbiosis and KRAS mutations in CRC remains unclear. 

To investigate further, Dr. Tang and colleagues used 16s rRNA sequencing to analyze stool samples from 94 patients with CRC, including 24 with KRAS-mutated CRC and 70 with KRAS wild-type (nonmutated) CRC. 

The researchers identified 26 distinct types of gut microbiota with statistically significant differences in abundance between the KRAS mutant and KRAS wild-type CRC patients.

At the genus level, Fusobacterium, Clostridium, and Shewanella were all abundant in the KRAS mutant group. 

Fusobacterium is a Gram-negative microbe found in the gastrointestinal tract and the oral cavity. Recent studies have established a strong link between Fusobacterium and CRC development. Other work found elevated levels of Fusobacterium nucleatum were not only closely associated with KRAS mutation but also correlated with chemoresistance in CRC.

Clostridium produces metabolites in the large intestine, which are known to cause DNA damage and trigger inflammatory responses, thereby increasing the risk of CRC development. 

Similarly, Shewanella has been proven to be a contributor to CRC development.

The researchers say it’s “plausible” to consider all three as potential noninvasive biomarkers for identifying KRAS mutation in CRC patients.

In contrast, Bifidobacterium and Akkermansia were abundant in the KRAS wild-type group. 

Bifidobacterium is a probiotic with antitumor activity and Akkermansia is a Gram-negative anaerobic bacterium abundant in the gut and currently recognized as a potential probiotic. 

The researchers speculated that CRC patients may have a reduced likelihood of developing KRAS mutation in the presence of Bifidobacterium and Akkermansia.

Analyses of biological pathways of gut microbiota associated with KRAS mutation status in CRC revealed a significantly higher abundance of the isoflavonoid biosynthesis pathway in the KRAS wild-type group compared with the KRAS mutant group.

“In comparison to KRAS mutant CRC, it is postulated that KRAS wild-type CRC may be less aggressive due to the upregulation of the isoflavonoid biosynthesis pathway, which may inhibit CRC development and progression,” the authors wrote.

Promising Predictive Model

Dr. Tang and colleagues also developed a machine learning model to predict KRAS mutation status in CRC patients based on the gut microbiota signature in KRAS mutant CRC. 

The initial results underscore the model’s predictive efficacy and suggest that it has “considerable potential for clinical application, offering a novel dimension in the prediction of KRAS mutation status among CRC patients in a clinical setting,” the authors wrote. 

They caution that the model requires data from a larger cohort to improve its efficacy, and they plan to do larger studies to validate the findings. 

The study had no commercial funding. The authors declared no relevant conflicts of interest. 

A version of this article appeared on Medscape.com.

TOPLINE:

An analysis of molecular-targeted cancer drug therapies recently approved in the United States found that fewer than one-third demonstrated substantial clinical benefits at the time of approval.

METHODOLOGY:

• The strength and quality of evidence supporting genome-targeted cancer drug approvals vary. A big reason is the growing number of cancer drug approvals based on surrogate endpoints, such as disease-free and progression-free survival, instead of clinical endpoints, such as overall survival or quality of life. The US Food and Drug Administration (FDA) has also approved genome-targeted cancer drugs based on phase 1 or single-arm trials.
• Given these less rigorous considerations for approval, “the validity and value of the targets and surrogate measures underlying FDA genome-targeted cancer drug approvals are uncertain,” the researchers explained.
• In the current analysis, researchers assessed the validity of the molecular targets as well as the clinical benefits of genome-targeted cancer drugs approved in the United States from 2015 to 2022 based on results from pivotal trials.
• The researchers evaluated the strength of evidence supporting molecular targetability using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) and the clinical benefit using the ESMO–Magnitude of Clinical Benefit Scale (ESMO-MCBS).
• The authors defined a substantial clinical benefit as an A or B grade for curative intent and a 4 or 5 for noncurative intent. High-benefit genomic-based cancer treatments were defined as those associated with a substantial clinical benefit (ESMO-MCBS) and that qualified as ESCAT category level I-A (a clinical benefit based on prospective randomized data) or I-B (prospective nonrandomized data).

TAKEAWAY:

• The analyses focused on 50 molecular-targeted cancer drugs covering 84 indications. Of which, 45 indications (54%) were approved based on phase 1 or 2 pivotal trials, 45 (54%) were supported by single-arm pivotal trials and the remaining 39 (46%) by randomized trial, and 48 (57%) were approved based on subgroup analyses.
• Among the 84 indications, more than half (55%) of the pivotal trials supporting approval used overall response rate as a primary endpoint, 31% used progression-free survival, and 6% used disease-free survival. Only seven indications (8%) were supported by pivotal trials demonstrating an improvement in overall survival.
• Among the 84 trials, 24 (29%) met the ESMO-MCBS threshold for substantial clinical benefit.
• Overall, when combining all ratings, only 24 of the 84 indications (29%) were considered high-benefit genomic-based cancer treatments.

IN PRACTICE:

“We applied the ESMO-MCBS and ESCAT value frameworks to identify therapies and molecular targets providing high clinical value that should be widely available to patients” and “found that drug indications supported by these characteristics represent a minority of cancer drug approvals in recent years,” the authors said. Using these value frameworks could help payers, governments, and individual patients “prioritize the availability of high-value molecular-targeted therapies.”

SOURCE:

The study, with first author Ariadna Tibau, MD, PhD, Brigham and Women’s Hospital and Harvard Medical School, Boston, was published online in JAMA Oncology.

LIMITATIONS:

The study evaluated only trials that supported regulatory approval and did not include outcomes of postapproval clinical studies, which could lead to changes in ESMO-MCBS grades and ESCAT levels of evidence over time.

DISCLOSURES:

The study was funded by the Kaiser Permanente Institute for Health Policy, Arnold Ventures, and the Commonwealth Fund. The authors had no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

An analysis of molecular-targeted cancer drug therapies recently approved in the United States found that fewer than one-third demonstrated substantial clinical benefits at the time of approval.

METHODOLOGY:

• The strength and quality of evidence supporting genome-targeted cancer drug approvals vary. A big reason is the growing number of cancer drug approvals based on surrogate endpoints, such as disease-free and progression-free survival, instead of clinical endpoints, such as overall survival or quality of life. The US Food and Drug Administration (FDA) has also approved genome-targeted cancer drugs based on phase 1 or single-arm trials.
• Given these less rigorous considerations for approval, “the validity and value of the targets and surrogate measures underlying FDA genome-targeted cancer drug approvals are uncertain,” the researchers explained.
• In the current analysis, researchers assessed the validity of the molecular targets as well as the clinical benefits of genome-targeted cancer drugs approved in the United States from 2015 to 2022 based on results from pivotal trials.
• The researchers evaluated the strength of evidence supporting molecular targetability using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) and the clinical benefit using the ESMO–Magnitude of Clinical Benefit Scale (ESMO-MCBS).
• The authors defined a substantial clinical benefit as an A or B grade for curative intent and a 4 or 5 for noncurative intent. High-benefit genomic-based cancer treatments were defined as those associated with a substantial clinical benefit (ESMO-MCBS) and that qualified as ESCAT category level I-A (a clinical benefit based on prospective randomized data) or I-B (prospective nonrandomized data).

TAKEAWAY:

• The analyses focused on 50 molecular-targeted cancer drugs covering 84 indications. Of which, 45 indications (54%) were approved based on phase 1 or 2 pivotal trials, 45 (54%) were supported by single-arm pivotal trials and the remaining 39 (46%) by randomized trial, and 48 (57%) were approved based on subgroup analyses.
• Among the 84 indications, more than half (55%) of the pivotal trials supporting approval used overall response rate as a primary endpoint, 31% used progression-free survival, and 6% used disease-free survival. Only seven indications (8%) were supported by pivotal trials demonstrating an improvement in overall survival.
• Among the 84 trials, 24 (29%) met the ESMO-MCBS threshold for substantial clinical benefit.
• Overall, when combining all ratings, only 24 of the 84 indications (29%) were considered high-benefit genomic-based cancer treatments.

IN PRACTICE:

“We applied the ESMO-MCBS and ESCAT value frameworks to identify therapies and molecular targets providing high clinical value that should be widely available to patients” and “found that drug indications supported by these characteristics represent a minority of cancer drug approvals in recent years,” the authors said. Using these value frameworks could help payers, governments, and individual patients “prioritize the availability of high-value molecular-targeted therapies.”

SOURCE:

The study, with first author Ariadna Tibau, MD, PhD, Brigham and Women’s Hospital and Harvard Medical School, Boston, was published online in JAMA Oncology.

LIMITATIONS:

The study evaluated only trials that supported regulatory approval and did not include outcomes of postapproval clinical studies, which could lead to changes in ESMO-MCBS grades and ESCAT levels of evidence over time.

DISCLOSURES:

The study was funded by the Kaiser Permanente Institute for Health Policy, Arnold Ventures, and the Commonwealth Fund. The authors had no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

An analysis of molecular-targeted cancer drug therapies recently approved in the United States found that fewer than one-third demonstrated substantial clinical benefits at the time of approval.

METHODOLOGY:

• The strength and quality of evidence supporting genome-targeted cancer drug approvals vary. A big reason is the growing number of cancer drug approvals based on surrogate endpoints, such as disease-free and progression-free survival, instead of clinical endpoints, such as overall survival or quality of life. The US Food and Drug Administration (FDA) has also approved genome-targeted cancer drugs based on phase 1 or single-arm trials.
• Given these less rigorous considerations for approval, “the validity and value of the targets and surrogate measures underlying FDA genome-targeted cancer drug approvals are uncertain,” the researchers explained.
• In the current analysis, researchers assessed the validity of the molecular targets as well as the clinical benefits of genome-targeted cancer drugs approved in the United States from 2015 to 2022 based on results from pivotal trials.
• The researchers evaluated the strength of evidence supporting molecular targetability using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) and the clinical benefit using the ESMO–Magnitude of Clinical Benefit Scale (ESMO-MCBS).
• The authors defined a substantial clinical benefit as an A or B grade for curative intent and a 4 or 5 for noncurative intent. High-benefit genomic-based cancer treatments were defined as those associated with a substantial clinical benefit (ESMO-MCBS) and that qualified as ESCAT category level I-A (a clinical benefit based on prospective randomized data) or I-B (prospective nonrandomized data).

TAKEAWAY:

• The analyses focused on 50 molecular-targeted cancer drugs covering 84 indications. Of which, 45 indications (54%) were approved based on phase 1 or 2 pivotal trials, 45 (54%) were supported by single-arm pivotal trials and the remaining 39 (46%) by randomized trial, and 48 (57%) were approved based on subgroup analyses.
• Among the 84 indications, more than half (55%) of the pivotal trials supporting approval used overall response rate as a primary endpoint, 31% used progression-free survival, and 6% used disease-free survival. Only seven indications (8%) were supported by pivotal trials demonstrating an improvement in overall survival.
• Among the 84 trials, 24 (29%) met the ESMO-MCBS threshold for substantial clinical benefit.
• Overall, when combining all ratings, only 24 of the 84 indications (29%) were considered high-benefit genomic-based cancer treatments.

IN PRACTICE:

“We applied the ESMO-MCBS and ESCAT value frameworks to identify therapies and molecular targets providing high clinical value that should be widely available to patients” and “found that drug indications supported by these characteristics represent a minority of cancer drug approvals in recent years,” the authors said. Using these value frameworks could help payers, governments, and individual patients “prioritize the availability of high-value molecular-targeted therapies.”

SOURCE:

The study, with first author Ariadna Tibau, MD, PhD, Brigham and Women’s Hospital and Harvard Medical School, Boston, was published online in JAMA Oncology.

LIMITATIONS:

The study evaluated only trials that supported regulatory approval and did not include outcomes of postapproval clinical studies, which could lead to changes in ESMO-MCBS grades and ESCAT levels of evidence over time.

DISCLOSURES:

The study was funded by the Kaiser Permanente Institute for Health Policy, Arnold Ventures, and the Commonwealth Fund. The authors had no relevant disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — A new cell-free DNA (cfDNA)-based blood test shows promising performance in detecting colorectal cancer and advanced precancerous lesions, say the authors of new research.

Rachel B. Issaka, MD, MAS, of the Fred Hutchinson Cancer Center, Seattle, presented the clinical data, which was published in The New England Journal of Medicine, at the American Association for Cancer Research annual meeting.

Issaka_Rachel_WASH_web.jpg

The authors of the study evaluated the performance of a cfDNA blood-based test in a population eligible for colorectal cancer screening. The researchers found that the test had high sensitivity for the detection of colorectal cancer and high specificity for advanced precancerous lesions.

This novel blood test could improve screening adherence and, ultimately, reduce colorectal cancer-related mortality, Dr. Issaka said during her presentation.

“This test has the potential to help us reach the 80% screening target in colorectal cancer. However, this will depend on many factors, including access, implementation, follow-up colonoscopy, and characteristics of the test,” Dr. Issaka said in an interview.

She added that, when approved for broader use, anyone who wants to use this blood test for colorectal cancer screening should have a frank conversation with their healthcare provider.

“Considering the person’s age, medical history, family history, and any potential symptoms, and how the test performs will dictate if it’s the right test for that person versus another screening strategy,” Dr. Issaka explained.
 

The Blood Test Detects Colorectal Cancer With High Accuracy

The investigators of the observational ECLIPSE trial evaluated the performance of the cfDNA-based blood test in 7861 individuals who were eligible for colorectal cancer screening. The study population included people from more than 200 rural and urban sites across 34 states, including community hospitals, private practices, gastroenterology clinics, and academic centers. “The study enrolled a diverse cohort that is reflective of the demographics of the intended use population in the US,” Dr. Issaka said during her talk.

The co-primary outcomes of the study were the test’s sensitivity for detecting colorectal cancer and its specificity for identifying advanced neoplasia.

In her presentation, Dr. Issaka highlighted that the test had 83.1% (95% confidence interval [CI], 72.2%-90.3%) sensitivity for the detection of colorectal cancer, meaning that it was able to correctly identify most participants with the disease. The test’s sensitivity was even higher (87.5%; 95% CI, 75.3%-94.1%) for stage I, II, or III colorectal cancer. “These are the stages at which early intervention can have the greatest impact on patient prognosis,” Dr. Issaka said.

Moreover, the blood test showed 89.6% (95% CI, 88.8%-90.3%) specificity for advanced neoplasia, including colorectal cancer and advanced precancerous lesions. The specificity of the test for negative colonoscopy results (no colorectal cancer, advanced precancerous lesions, or nonadvanced precancerous lesions) was 89.9% (95% CI, 89.0%-90.7%).

Dr. Issaka highlighted that this cfDNA assay is the first blood-based test with performance comparable to current guideline-recommended noninvasive options for CRC.
 

The Blood Test Shows Limited Ability To Detect Advanced Precancerous Lesions

During her presentation, Dr. Issaka acknowledged that the cfDNA-based blood test had a lower sensitivity (13.2%; 95% CI, 11.3%-15.3%) for the detection of advanced precancerous lesions, suggesting that it may be more effective at identifying established cancers than early-stage precancerous changes. Low sensitivity was also observed for high-grade dysplasia (22.6%; 95% CI, 11.4%-39.8%). However, she emphasized that the test could still play a valuable role in a comprehensive screening approach, potentially serving as a first-line tool to identify individuals who would then undergo follow-up colonoscopy.

“Although blood-based tests perform well at finding cancers, they do not do so well at finding precancerous polyps. This is relevant because colorectal cancer is one of the few cancers that we can prevent by finding and removing precancerous polyps,” Folasade P. May, MD, PhD, MPhil, said in an interview.

“Users must also understand that if the test result is abnormal, a colonoscopy is required to look for cancers and polyps that might have caused the abnormal result,” added Dr. May, associate professor at UCLA. She was not involved in the study.
 

Clinical Implications and Future Steps

According to the study published in the NEJM, colorectal cancer is the third most commonly diagnosed cancer in the United States, and early detection is crucial for effective treatment. However, over a third of eligible individuals are not up to date with recommended screening.

During her talk, Dr. Issaka noted that colonoscopy is the most commonly used screening method for colorectal cancer. What contributes to the low adherence to getting a colonoscopy among the eligible population is that some find it inconvenient, and the test is invasive, she added.

According to Dr. May, the key advantage of cfDNA-based screening is that many people will find it easier to complete a blood test than the currently available screening tests.

“This option may allow us to screen individuals that we have previously struggled to convince to get screened for colorectal cancer,” she said.

In an interview, Dr. Issaka acknowledged that the potential public health impact of any noninvasive screening test depends on how many people with abnormal results complete a follow-up colonoscopy. “This is an important quality metric to track,” she said.

In an interview, Dr. Issaka emphasized that comparing this cfDNA blood test with emerging blood tests and other noninvasive screening strategies will empower patients and clinicians to select the right test at the right time for the right patient.

She added that the study was conducted in an average-risk screening population and that further research is needed to evaluate the test’s performance in higher-risk groups and to assess its real-world impact on screening adherence and colorectal cancer-related outcomes.

Commenting on potential challenges with implementing this cfDNA blood test in clinical practice, Dr. May said, “As we consider incorporating blood-based tests into clinical practice, some challenges include cost, equitable access to tests and follow-up, performance in young adults who are newly eligible for screening, and follow-up after abnormal results.”

She added that, if there is uptake of these tests, it will be important to track how that impacts colorectal cancer screening rates, stage at diagnosis, and whether there is stage migration, incidence, and mortality.

“At this time, I feel that these tests are appropriate for individuals who will not or cannot participate in one of the currently recommended screening tests. These include colonoscopy and stool-based tests, like FIT and FIT-DNA,” Dr. May concluded.

Dr. Issaka reported financial relationships with the National Institutes of Health/National Cancer Institute, American College of Gastroenterology, and Guardant Health Inc. Dr. May reported financial relationships with Takeda, Medtronic, Johnson & Johnson, Saint Supply, Exact Sciences, Freenome, Geneoscopy, Guardant Health, InterVenn, Natura, National Institutes of Health/National Cancer Institute, Veterans Affairs HSR&D, Broad Institute, Stand up to Cancer, and NRG Oncology.

SAN DIEGO — A new cell-free DNA (cfDNA)-based blood test shows promising performance in detecting colorectal cancer and advanced precancerous lesions, say the authors of new research.

Rachel B. Issaka, MD, MAS, of the Fred Hutchinson Cancer Center, Seattle, presented the clinical data, which was published in The New England Journal of Medicine, at the American Association for Cancer Research annual meeting.

Issaka_Rachel_WASH_web.jpg

The authors of the study evaluated the performance of a cfDNA blood-based test in a population eligible for colorectal cancer screening. The researchers found that the test had high sensitivity for the detection of colorectal cancer and high specificity for advanced precancerous lesions.

This novel blood test could improve screening adherence and, ultimately, reduce colorectal cancer-related mortality, Dr. Issaka said during her presentation.

“This test has the potential to help us reach the 80% screening target in colorectal cancer. However, this will depend on many factors, including access, implementation, follow-up colonoscopy, and characteristics of the test,” Dr. Issaka said in an interview.

She added that, when approved for broader use, anyone who wants to use this blood test for colorectal cancer screening should have a frank conversation with their healthcare provider.

“Considering the person’s age, medical history, family history, and any potential symptoms, and how the test performs will dictate if it’s the right test for that person versus another screening strategy,” Dr. Issaka explained.
 

The Blood Test Detects Colorectal Cancer With High Accuracy

The investigators of the observational ECLIPSE trial evaluated the performance of the cfDNA-based blood test in 7861 individuals who were eligible for colorectal cancer screening. The study population included people from more than 200 rural and urban sites across 34 states, including community hospitals, private practices, gastroenterology clinics, and academic centers. “The study enrolled a diverse cohort that is reflective of the demographics of the intended use population in the US,” Dr. Issaka said during her talk.

The co-primary outcomes of the study were the test’s sensitivity for detecting colorectal cancer and its specificity for identifying advanced neoplasia.

In her presentation, Dr. Issaka highlighted that the test had 83.1% (95% confidence interval [CI], 72.2%-90.3%) sensitivity for the detection of colorectal cancer, meaning that it was able to correctly identify most participants with the disease. The test’s sensitivity was even higher (87.5%; 95% CI, 75.3%-94.1%) for stage I, II, or III colorectal cancer. “These are the stages at which early intervention can have the greatest impact on patient prognosis,” Dr. Issaka said.

Moreover, the blood test showed 89.6% (95% CI, 88.8%-90.3%) specificity for advanced neoplasia, including colorectal cancer and advanced precancerous lesions. The specificity of the test for negative colonoscopy results (no colorectal cancer, advanced precancerous lesions, or nonadvanced precancerous lesions) was 89.9% (95% CI, 89.0%-90.7%).

Dr. Issaka highlighted that this cfDNA assay is the first blood-based test with performance comparable to current guideline-recommended noninvasive options for CRC.
 

The Blood Test Shows Limited Ability To Detect Advanced Precancerous Lesions

During her presentation, Dr. Issaka acknowledged that the cfDNA-based blood test had a lower sensitivity (13.2%; 95% CI, 11.3%-15.3%) for the detection of advanced precancerous lesions, suggesting that it may be more effective at identifying established cancers than early-stage precancerous changes. Low sensitivity was also observed for high-grade dysplasia (22.6%; 95% CI, 11.4%-39.8%). However, she emphasized that the test could still play a valuable role in a comprehensive screening approach, potentially serving as a first-line tool to identify individuals who would then undergo follow-up colonoscopy.

“Although blood-based tests perform well at finding cancers, they do not do so well at finding precancerous polyps. This is relevant because colorectal cancer is one of the few cancers that we can prevent by finding and removing precancerous polyps,” Folasade P. May, MD, PhD, MPhil, said in an interview.

“Users must also understand that if the test result is abnormal, a colonoscopy is required to look for cancers and polyps that might have caused the abnormal result,” added Dr. May, associate professor at UCLA. She was not involved in the study.
 

Clinical Implications and Future Steps

According to the study published in the NEJM, colorectal cancer is the third most commonly diagnosed cancer in the United States, and early detection is crucial for effective treatment. However, over a third of eligible individuals are not up to date with recommended screening.

During her talk, Dr. Issaka noted that colonoscopy is the most commonly used screening method for colorectal cancer. What contributes to the low adherence to getting a colonoscopy among the eligible population is that some find it inconvenient, and the test is invasive, she added.

According to Dr. May, the key advantage of cfDNA-based screening is that many people will find it easier to complete a blood test than the currently available screening tests.

“This option may allow us to screen individuals that we have previously struggled to convince to get screened for colorectal cancer,” she said.

In an interview, Dr. Issaka acknowledged that the potential public health impact of any noninvasive screening test depends on how many people with abnormal results complete a follow-up colonoscopy. “This is an important quality metric to track,” she said.

In an interview, Dr. Issaka emphasized that comparing this cfDNA blood test with emerging blood tests and other noninvasive screening strategies will empower patients and clinicians to select the right test at the right time for the right patient.

She added that the study was conducted in an average-risk screening population and that further research is needed to evaluate the test’s performance in higher-risk groups and to assess its real-world impact on screening adherence and colorectal cancer-related outcomes.

Commenting on potential challenges with implementing this cfDNA blood test in clinical practice, Dr. May said, “As we consider incorporating blood-based tests into clinical practice, some challenges include cost, equitable access to tests and follow-up, performance in young adults who are newly eligible for screening, and follow-up after abnormal results.”

She added that, if there is uptake of these tests, it will be important to track how that impacts colorectal cancer screening rates, stage at diagnosis, and whether there is stage migration, incidence, and mortality.

“At this time, I feel that these tests are appropriate for individuals who will not or cannot participate in one of the currently recommended screening tests. These include colonoscopy and stool-based tests, like FIT and FIT-DNA,” Dr. May concluded.

Dr. Issaka reported financial relationships with the National Institutes of Health/National Cancer Institute, American College of Gastroenterology, and Guardant Health Inc. Dr. May reported financial relationships with Takeda, Medtronic, Johnson & Johnson, Saint Supply, Exact Sciences, Freenome, Geneoscopy, Guardant Health, InterVenn, Natura, National Institutes of Health/National Cancer Institute, Veterans Affairs HSR&D, Broad Institute, Stand up to Cancer, and NRG Oncology.

SAN DIEGO — A new cell-free DNA (cfDNA)-based blood test shows promising performance in detecting colorectal cancer and advanced precancerous lesions, say the authors of new research.

Rachel B. Issaka, MD, MAS, of the Fred Hutchinson Cancer Center, Seattle, presented the clinical data, which was published in The New England Journal of Medicine, at the American Association for Cancer Research annual meeting.

Issaka_Rachel_WASH_web.jpg

The authors of the study evaluated the performance of a cfDNA blood-based test in a population eligible for colorectal cancer screening. The researchers found that the test had high sensitivity for the detection of colorectal cancer and high specificity for advanced precancerous lesions.

This novel blood test could improve screening adherence and, ultimately, reduce colorectal cancer-related mortality, Dr. Issaka said during her presentation.

“This test has the potential to help us reach the 80% screening target in colorectal cancer. However, this will depend on many factors, including access, implementation, follow-up colonoscopy, and characteristics of the test,” Dr. Issaka said in an interview.

She added that, when approved for broader use, anyone who wants to use this blood test for colorectal cancer screening should have a frank conversation with their healthcare provider.

“Considering the person’s age, medical history, family history, and any potential symptoms, and how the test performs will dictate if it’s the right test for that person versus another screening strategy,” Dr. Issaka explained.
 

The Blood Test Detects Colorectal Cancer With High Accuracy

The investigators of the observational ECLIPSE trial evaluated the performance of the cfDNA-based blood test in 7861 individuals who were eligible for colorectal cancer screening. The study population included people from more than 200 rural and urban sites across 34 states, including community hospitals, private practices, gastroenterology clinics, and academic centers. “The study enrolled a diverse cohort that is reflective of the demographics of the intended use population in the US,” Dr. Issaka said during her talk.

The co-primary outcomes of the study were the test’s sensitivity for detecting colorectal cancer and its specificity for identifying advanced neoplasia.

In her presentation, Dr. Issaka highlighted that the test had 83.1% (95% confidence interval [CI], 72.2%-90.3%) sensitivity for the detection of colorectal cancer, meaning that it was able to correctly identify most participants with the disease. The test’s sensitivity was even higher (87.5%; 95% CI, 75.3%-94.1%) for stage I, II, or III colorectal cancer. “These are the stages at which early intervention can have the greatest impact on patient prognosis,” Dr. Issaka said.

Moreover, the blood test showed 89.6% (95% CI, 88.8%-90.3%) specificity for advanced neoplasia, including colorectal cancer and advanced precancerous lesions. The specificity of the test for negative colonoscopy results (no colorectal cancer, advanced precancerous lesions, or nonadvanced precancerous lesions) was 89.9% (95% CI, 89.0%-90.7%).

Dr. Issaka highlighted that this cfDNA assay is the first blood-based test with performance comparable to current guideline-recommended noninvasive options for CRC.
 

The Blood Test Shows Limited Ability To Detect Advanced Precancerous Lesions

During her presentation, Dr. Issaka acknowledged that the cfDNA-based blood test had a lower sensitivity (13.2%; 95% CI, 11.3%-15.3%) for the detection of advanced precancerous lesions, suggesting that it may be more effective at identifying established cancers than early-stage precancerous changes. Low sensitivity was also observed for high-grade dysplasia (22.6%; 95% CI, 11.4%-39.8%). However, she emphasized that the test could still play a valuable role in a comprehensive screening approach, potentially serving as a first-line tool to identify individuals who would then undergo follow-up colonoscopy.

“Although blood-based tests perform well at finding cancers, they do not do so well at finding precancerous polyps. This is relevant because colorectal cancer is one of the few cancers that we can prevent by finding and removing precancerous polyps,” Folasade P. May, MD, PhD, MPhil, said in an interview.

“Users must also understand that if the test result is abnormal, a colonoscopy is required to look for cancers and polyps that might have caused the abnormal result,” added Dr. May, associate professor at UCLA. She was not involved in the study.
 

Clinical Implications and Future Steps

According to the study published in the NEJM, colorectal cancer is the third most commonly diagnosed cancer in the United States, and early detection is crucial for effective treatment. However, over a third of eligible individuals are not up to date with recommended screening.

During her talk, Dr. Issaka noted that colonoscopy is the most commonly used screening method for colorectal cancer. What contributes to the low adherence to getting a colonoscopy among the eligible population is that some find it inconvenient, and the test is invasive, she added.

According to Dr. May, the key advantage of cfDNA-based screening is that many people will find it easier to complete a blood test than the currently available screening tests.

“This option may allow us to screen individuals that we have previously struggled to convince to get screened for colorectal cancer,” she said.

In an interview, Dr. Issaka acknowledged that the potential public health impact of any noninvasive screening test depends on how many people with abnormal results complete a follow-up colonoscopy. “This is an important quality metric to track,” she said.

In an interview, Dr. Issaka emphasized that comparing this cfDNA blood test with emerging blood tests and other noninvasive screening strategies will empower patients and clinicians to select the right test at the right time for the right patient.

She added that the study was conducted in an average-risk screening population and that further research is needed to evaluate the test’s performance in higher-risk groups and to assess its real-world impact on screening adherence and colorectal cancer-related outcomes.

Commenting on potential challenges with implementing this cfDNA blood test in clinical practice, Dr. May said, “As we consider incorporating blood-based tests into clinical practice, some challenges include cost, equitable access to tests and follow-up, performance in young adults who are newly eligible for screening, and follow-up after abnormal results.”

She added that, if there is uptake of these tests, it will be important to track how that impacts colorectal cancer screening rates, stage at diagnosis, and whether there is stage migration, incidence, and mortality.

“At this time, I feel that these tests are appropriate for individuals who will not or cannot participate in one of the currently recommended screening tests. These include colonoscopy and stool-based tests, like FIT and FIT-DNA,” Dr. May concluded.

Dr. Issaka reported financial relationships with the National Institutes of Health/National Cancer Institute, American College of Gastroenterology, and Guardant Health Inc. Dr. May reported financial relationships with Takeda, Medtronic, Johnson & Johnson, Saint Supply, Exact Sciences, Freenome, Geneoscopy, Guardant Health, InterVenn, Natura, National Institutes of Health/National Cancer Institute, Veterans Affairs HSR&D, Broad Institute, Stand up to Cancer, and NRG Oncology.

TOPLINE:

For individuals aged 45-49 years at average risk for colorectal cancer (CRC), the adenoma detection rate (ADR) in screening colonoscopies is 28%, which is comparable with rates seen in those aged 50-54 years.

METHODOLOGY:

• The rising incidence of CRC in younger populations prompted most guidelines to recommend screening to start at age 45. The impact of lowering the screening age on adenoma and sessile serrated lesion detection rates remains unclear, however.
• Researchers conducted a systematic review and meta-analysis of 16 studies; all studies were retrospective except one.
• Patients aged 45-49 years undergoing colonoscopy for any indication were included, with a separate analysis of patients in that age group at average CRC risk undergoing screening colonoscopies.
• The primary outcome was the overall detection rates of adenomas and sessile serrated lesions for colonoscopies performed for any indication.

TAKEAWAY:

• Across 15 studies, 41,709 adenomas were detected in 150,436 colonoscopies performed for any indication, resulting in a pooled overall ADR of 23.1%.
• Across six studies, 1162 sessile serrated lesions were reported in 11,457 colonoscopies performed for any indication, with a pooled detection rate of 6.3%.
• Across seven studies, the pooled ADR in screening colonoscopies performed on individuals with average CRC risk was 28.2%, which is comparable with that of 50- to 54-year-old individuals undergoing screening colonoscopy. There was not enough data to calculate the sessile serrated lesion detection rate in average-risk patients.
• The ADR was higher in the United States and Canada (26.1%) compared with studies from Asia (16.9%).

IN PRACTICE:

“The comparable detection rates of precancerous lesions in this age group to those 50 to 54 years old support starting CRC screening at 45 years of age,” the authors wrote.

SOURCE:

This study, led by Mohamed Abdallah, MD, Division of Gastroenterology and Hepatology, University of Minnesota Medical Center, Minneapolis, was published online in The American Journal of Gastroenterology.

LIMITATIONS:

The inclusion of retrospective studies has an inherent bias. The heterogeneity between studies may limit the generalizability of the findings. Some studies that reported detection rates included individuals at both average and high risk for CRC, so they could not be used to evaluate ADRs in individuals with an average risk for CRC. Data duplication could not be ruled out.

DISCLOSURES:

The study did not receive any funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

For individuals aged 45-49 years at average risk for colorectal cancer (CRC), the adenoma detection rate (ADR) in screening colonoscopies is 28%, which is comparable with rates seen in those aged 50-54 years.

METHODOLOGY:

• The rising incidence of CRC in younger populations prompted most guidelines to recommend screening to start at age 45. The impact of lowering the screening age on adenoma and sessile serrated lesion detection rates remains unclear, however.
• Researchers conducted a systematic review and meta-analysis of 16 studies; all studies were retrospective except one.
• Patients aged 45-49 years undergoing colonoscopy for any indication were included, with a separate analysis of patients in that age group at average CRC risk undergoing screening colonoscopies.
• The primary outcome was the overall detection rates of adenomas and sessile serrated lesions for colonoscopies performed for any indication.

TAKEAWAY:

• Across 15 studies, 41,709 adenomas were detected in 150,436 colonoscopies performed for any indication, resulting in a pooled overall ADR of 23.1%.
• Across six studies, 1162 sessile serrated lesions were reported in 11,457 colonoscopies performed for any indication, with a pooled detection rate of 6.3%.
• Across seven studies, the pooled ADR in screening colonoscopies performed on individuals with average CRC risk was 28.2%, which is comparable with that of 50- to 54-year-old individuals undergoing screening colonoscopy. There was not enough data to calculate the sessile serrated lesion detection rate in average-risk patients.
• The ADR was higher in the United States and Canada (26.1%) compared with studies from Asia (16.9%).

IN PRACTICE:

“The comparable detection rates of precancerous lesions in this age group to those 50 to 54 years old support starting CRC screening at 45 years of age,” the authors wrote.

SOURCE:

This study, led by Mohamed Abdallah, MD, Division of Gastroenterology and Hepatology, University of Minnesota Medical Center, Minneapolis, was published online in The American Journal of Gastroenterology.

LIMITATIONS:

The inclusion of retrospective studies has an inherent bias. The heterogeneity between studies may limit the generalizability of the findings. Some studies that reported detection rates included individuals at both average and high risk for CRC, so they could not be used to evaluate ADRs in individuals with an average risk for CRC. Data duplication could not be ruled out.

DISCLOSURES:

The study did not receive any funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

For individuals aged 45-49 years at average risk for colorectal cancer (CRC), the adenoma detection rate (ADR) in screening colonoscopies is 28%, which is comparable with rates seen in those aged 50-54 years.

METHODOLOGY:

• The rising incidence of CRC in younger populations prompted most guidelines to recommend screening to start at age 45. The impact of lowering the screening age on adenoma and sessile serrated lesion detection rates remains unclear, however.
• Researchers conducted a systematic review and meta-analysis of 16 studies; all studies were retrospective except one.
• Patients aged 45-49 years undergoing colonoscopy for any indication were included, with a separate analysis of patients in that age group at average CRC risk undergoing screening colonoscopies.
• The primary outcome was the overall detection rates of adenomas and sessile serrated lesions for colonoscopies performed for any indication.

TAKEAWAY:

• Across 15 studies, 41,709 adenomas were detected in 150,436 colonoscopies performed for any indication, resulting in a pooled overall ADR of 23.1%.
• Across six studies, 1162 sessile serrated lesions were reported in 11,457 colonoscopies performed for any indication, with a pooled detection rate of 6.3%.
• Across seven studies, the pooled ADR in screening colonoscopies performed on individuals with average CRC risk was 28.2%, which is comparable with that of 50- to 54-year-old individuals undergoing screening colonoscopy. There was not enough data to calculate the sessile serrated lesion detection rate in average-risk patients.
• The ADR was higher in the United States and Canada (26.1%) compared with studies from Asia (16.9%).

IN PRACTICE:

“The comparable detection rates of precancerous lesions in this age group to those 50 to 54 years old support starting CRC screening at 45 years of age,” the authors wrote.

SOURCE:

This study, led by Mohamed Abdallah, MD, Division of Gastroenterology and Hepatology, University of Minnesota Medical Center, Minneapolis, was published online in The American Journal of Gastroenterology.

LIMITATIONS:

The inclusion of retrospective studies has an inherent bias. The heterogeneity between studies may limit the generalizability of the findings. Some studies that reported detection rates included individuals at both average and high risk for CRC, so they could not be used to evaluate ADRs in individuals with an average risk for CRC. Data duplication could not be ruled out.

DISCLOSURES:

The study did not receive any funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

Multitarget stool-based tests are showing promise for colorectal cancer (CRC) screening in average-risk individuals and could edge out the current standard fecal immunochemical test (FIT).

These new tests aren’t radical departures from the standard FIT. Like the standard test, the multitarget FIT uses antibodies to test for hemoglobin in stool samples. But these multitarget approaches take the standard FIT a step further by testing for additional DNA, RNA, or protein biomarkers associated with CRC to help improve early detection.

Currently, the US Preventive Services Task Force (USPSTF) recommends two FIT tests — standard FIT and stool FIT-DNA — as well as a third noninvasive CRC screening test, guaiac fecal occult blood test (gFOBT). gFOBT detects heme, a component of hemoglobin, through a chemical reaction.

But both standard FIT and stool FIT-DNA come with caveats. Compared to the standard test, FIT-DNA tends to be better at detecting traces of blood in the stool, and thus can uncover more instances of CRC or other advanced lesions. The flipside is that the DNA test also often leads to more false-positive findings.

In fact, the American College of Physicians does not recommend stool FIT-DNA for screening, citing issues such as cost — more than $600 per test vs about $30 for standard FIT — and the greater likelihood of false-positives compared with both standard FIT and gFOBT.

Given these trade-offs with current noninvasive screening options, developing a FIT option that can improve early detection of CRC and advanced precancerous lesions without increasing false-positives could make a big difference in outcomes. 

Three new noninvasive multitarget tests under investigation — an updated DNA-based test, Cologuard 2.0 (Exact Sciences; Madison, WI); an RNA-based test, ColoSense (Geneoscopy; St Louis, MO); and a protein-based test from CRCbioscreen (Amsterdam, the Netherlands) — may be able to do just that. 
 

Cologuard 2.0: Multitarget Stool DNA-Based Test

An updated version of the stool FIT-DNA is currently under development. Dubbed Next Generation Cologuard, or Cologuard 2.0, this multitarget test detects three novel methylated DNA markers along with fecal hemoglobin.

In a recent trial comparing Cologuard 2.0 vs standard FIT, 20,176 participants aged 40 years or older were screened with Cologuard 2.0 as well as standard FIT before they all also received a colonoscopy. The researchers compared findings with Cologuard 2.0 and standard FIT, which used a positivity cutoff ≥ 20 mcg hemoglobin/g feces. 

The researchers then assessed Cologuard 2.0’s sensitivity (a gauge of how well it detects disease that is truly present) and specificity (a measure of how well a test indicates the absence of disease when no disease is present) compared with standard FIT and the original Cologuard test.

Overall, Cologuard 2.0 demonstrated better sensitivity for CRC than did standard FIT (93.9% vs 67.3%, respectively) and for advanced precancerous lesions (43.4% vs 23.3%). The next-generation test, for instance, identified 92 of 98 participants with colonoscopy-confirmed CRC diagnoses vs 66 cases using standard FIT.

Compared with the original Cologuard, Cologuard 2.0’s sensitivity improved slightly for CRC, from 92% to 93.9%,; for advanced precancerous lesions, from 42% to 43.4%; and for high-grade dysplasia, from 69% to 75%. Specificity also improved with the latest version, from 87% to 90.6%. 

However, Cologuard 2.0’s specificity for advanced neoplasia was worse than that of standard FIT (90.6% vs 94.8%, respectively), which would increase the likelihood of false-positive findings.

Despite its lower specificity compared with standard FIT, Cologuard 2.0 has several advantages. The test can identify more people with CRC and advanced precancerous lesions than the standard test and can lead to fewer false-positives than the original Cologuard test.

Cologuard maker Exact Sciences has submitted trial data to the US Food and Drug Administration (FDA) for approval.
 

Multitarget Stool RNA-Based Test

ColoSense, an RNA-based stool test, looks for eight RNA biomarkers associated with CRC. 

The company says that RNA-based testing has an advantage over DNA biomarker assays, such as the currently marketed Cologuard test, because it isn›t subject to the age-related changes in DNA methylation that can throw off the results from DNA assays. 

Like Cologuard 2.0, Geneoscopy’s Colosense test is under review by the FDA.

The data Geneoscopy submitted to the FDA came from the CRC-PREVENT trial, which included 8920 participants who were screened with both ColoSense and standard FIT before all had a colonoscopy. The participants ranged in age from 45 to 90 years, with 22% between 45 and 50 years old, a population recently added to the USPSTF screening recommendations. 

ColoSense showed higher sensitivity than standard FIT for the presence of CRC (94% vs 78%, respectively) and advanced adenomas (46% vs 29%). In the group aged 45-50 years, the RNA-based test had a sensitivity of 100% for CRC, correctly identifying all five people with colonoscopy-confirmed CRC, and 45% for advanced adenomas.

However, ColoSense was less specific than standard FIT compared with negative colonoscopy findings (88% vs 96%, respectively) and negative findings for advanced lesions or CRC (85.5% vs 94.9%); thus, it was more likely to lead to false-positive results.

Overall, the investigators said ColoSense is comparable to Cologuard — its chief market rival — in terms of sensitivity for CRC and advanced adenomas but has higher sensitivity for colorectal neoplasia in people aged 50 years or younger.
 

Multitarget Protein-Based Test

The multitarget protein-based FIT uses antibodies to test for two additional proteins: calprotectin, an inflammatory marker associated with CRC, and serpin family F member 2, a protease inhibitor thought to be upregulated in colon cancer. 

A 2021 study of 1284 patients found that the sensitivity of the multitarget protein-based test was 42.9% for advanced neoplasias compared with 37.3% with standard FIT. Its specificity was similar to that of standard FIT, at 96.6% for advanced neoplasias. 

In a more recent report published in The Lancet Oncology, the team modeled three scenarios comparing the two FIT tests. These scenarios used different cutoff values for a test to be positive for CRC or an advanced lesion.

Overall, the analysis included stool samples from 13,187 patients aged 55-75 years who were in the Netherlands’ national CRC screening program. Stool samples were evaluated with both the multitarget test and the standard FIT, using a positivity cutoff ≥ 47 mcg hemoglobin/g feces. Colonoscopy data were available for only 1270 participants. 

In scenario 1, the multitarget test had a lower threshold for a positive test and consequently identified more precancerous lesions than the standard FIT (828 vs 354, respectively). The multitarget FIT identified a few more CRC cases: Of 29 colonoscopy-confirmed CRC cases, the multitarget FIT identified 26 vs 23 with standard FIT. 

But the multitarget FIT also had more than double the number of false-positives than the standard FIT (347 vs 161, respectively).

Perhaps the most telling comparison occurred in scenario 2, with both tests set at the same low positivity threshold to minimize false-positives.

As expected, the two tests had similar positivity rates for advanced lesions, with the multitarget test correctly identifying 22 of 29 people with CRC, one fewer than the standard test. The protein-based test identified slightly more people with advanced lesions (156 vs 136 with the standard test), leading to a higher sensitivity for advanced lesions. 

Most notably, the protein-based test resulted in fewer false-positives than did the standard test (295 vs 311, respectively) , resulting in a slightly higher specificity.

In this scenario, “a single screening round might not have the biggest impact on cancer incidence and mortality,” the authors said, but the higher detection rate would still accumulate over 20 years of testing. The authors estimated that, under this scenario, substituting the multitarget FIT for the standard test in the Netherlands’ CRC screening program could reduce CRC incidence by 5% and CRC mortality by 4%.

Gerrit Meijer, MD, PhD, a pathologist at the Netherlands Cancer Institute, and colleagues recently launched a company called CRCbioscreen to commercialize this multitarget FIT for large-scale programs. The company›s priority is to develop and validate a clinical-grade test to sell to federal governments with national screening programs, such as those throughout Europe, Australia, and Asia, Dr. Meijer told this news organization. Dr. Meijer expects this process will take about 4 years.

The test will be developed for the US market, but with no nationwide screening program in the United States, future availability will depend on interest from providers and institutions, noted Dr. Meijer, who is also chief scientific officer at CRCbioscreen.

Overall, these three new multitarget stool-based CRC screening tests could help catch more cancers and advanced precancerous lesions. And, if the tests have a high enough specificity, a negative test result could also allow people to forgo screening colonoscopy. 

Still, people with a positive FIT finding would require follow-up colonoscopy, but about 10% of patients decline colonoscopy following an abnormal FIT, Mark A. Lewis, MD, director of gastrointestinal oncology at Intermountain Health in Murray, Utah, told this news organization last year. That means that even if precancerous lesions and CRC are being caught earlier, treatment can’t be started unless people follow through with colonoscopy.

A version of this article appeared on Medscape.com.

Multitarget stool-based tests are showing promise for colorectal cancer (CRC) screening in average-risk individuals and could edge out the current standard fecal immunochemical test (FIT).

These new tests aren’t radical departures from the standard FIT. Like the standard test, the multitarget FIT uses antibodies to test for hemoglobin in stool samples. But these multitarget approaches take the standard FIT a step further by testing for additional DNA, RNA, or protein biomarkers associated with CRC to help improve early detection.

Currently, the US Preventive Services Task Force (USPSTF) recommends two FIT tests — standard FIT and stool FIT-DNA — as well as a third noninvasive CRC screening test, guaiac fecal occult blood test (gFOBT). gFOBT detects heme, a component of hemoglobin, through a chemical reaction.

But both standard FIT and stool FIT-DNA come with caveats. Compared to the standard test, FIT-DNA tends to be better at detecting traces of blood in the stool, and thus can uncover more instances of CRC or other advanced lesions. The flipside is that the DNA test also often leads to more false-positive findings.

In fact, the American College of Physicians does not recommend stool FIT-DNA for screening, citing issues such as cost — more than $600 per test vs about $30 for standard FIT — and the greater likelihood of false-positives compared with both standard FIT and gFOBT.

Given these trade-offs with current noninvasive screening options, developing a FIT option that can improve early detection of CRC and advanced precancerous lesions without increasing false-positives could make a big difference in outcomes. 

Three new noninvasive multitarget tests under investigation — an updated DNA-based test, Cologuard 2.0 (Exact Sciences; Madison, WI); an RNA-based test, ColoSense (Geneoscopy; St Louis, MO); and a protein-based test from CRCbioscreen (Amsterdam, the Netherlands) — may be able to do just that. 
 

Cologuard 2.0: Multitarget Stool DNA-Based Test

An updated version of the stool FIT-DNA is currently under development. Dubbed Next Generation Cologuard, or Cologuard 2.0, this multitarget test detects three novel methylated DNA markers along with fecal hemoglobin.

In a recent trial comparing Cologuard 2.0 vs standard FIT, 20,176 participants aged 40 years or older were screened with Cologuard 2.0 as well as standard FIT before they all also received a colonoscopy. The researchers compared findings with Cologuard 2.0 and standard FIT, which used a positivity cutoff ≥ 20 mcg hemoglobin/g feces. 

The researchers then assessed Cologuard 2.0’s sensitivity (a gauge of how well it detects disease that is truly present) and specificity (a measure of how well a test indicates the absence of disease when no disease is present) compared with standard FIT and the original Cologuard test.

Overall, Cologuard 2.0 demonstrated better sensitivity for CRC than did standard FIT (93.9% vs 67.3%, respectively) and for advanced precancerous lesions (43.4% vs 23.3%). The next-generation test, for instance, identified 92 of 98 participants with colonoscopy-confirmed CRC diagnoses vs 66 cases using standard FIT.

Compared with the original Cologuard, Cologuard 2.0’s sensitivity improved slightly for CRC, from 92% to 93.9%,; for advanced precancerous lesions, from 42% to 43.4%; and for high-grade dysplasia, from 69% to 75%. Specificity also improved with the latest version, from 87% to 90.6%. 

However, Cologuard 2.0’s specificity for advanced neoplasia was worse than that of standard FIT (90.6% vs 94.8%, respectively), which would increase the likelihood of false-positive findings.

Despite its lower specificity compared with standard FIT, Cologuard 2.0 has several advantages. The test can identify more people with CRC and advanced precancerous lesions than the standard test and can lead to fewer false-positives than the original Cologuard test.

Cologuard maker Exact Sciences has submitted trial data to the US Food and Drug Administration (FDA) for approval.
 

Multitarget Stool RNA-Based Test

ColoSense, an RNA-based stool test, looks for eight RNA biomarkers associated with CRC. 

The company says that RNA-based testing has an advantage over DNA biomarker assays, such as the currently marketed Cologuard test, because it isn›t subject to the age-related changes in DNA methylation that can throw off the results from DNA assays. 

Like Cologuard 2.0, Geneoscopy’s Colosense test is under review by the FDA.

The data Geneoscopy submitted to the FDA came from the CRC-PREVENT trial, which included 8920 participants who were screened with both ColoSense and standard FIT before all had a colonoscopy. The participants ranged in age from 45 to 90 years, with 22% between 45 and 50 years old, a population recently added to the USPSTF screening recommendations. 

ColoSense showed higher sensitivity than standard FIT for the presence of CRC (94% vs 78%, respectively) and advanced adenomas (46% vs 29%). In the group aged 45-50 years, the RNA-based test had a sensitivity of 100% for CRC, correctly identifying all five people with colonoscopy-confirmed CRC, and 45% for advanced adenomas.

However, ColoSense was less specific than standard FIT compared with negative colonoscopy findings (88% vs 96%, respectively) and negative findings for advanced lesions or CRC (85.5% vs 94.9%); thus, it was more likely to lead to false-positive results.

Overall, the investigators said ColoSense is comparable to Cologuard — its chief market rival — in terms of sensitivity for CRC and advanced adenomas but has higher sensitivity for colorectal neoplasia in people aged 50 years or younger.
 

Multitarget Protein-Based Test

The multitarget protein-based FIT uses antibodies to test for two additional proteins: calprotectin, an inflammatory marker associated with CRC, and serpin family F member 2, a protease inhibitor thought to be upregulated in colon cancer. 

A 2021 study of 1284 patients found that the sensitivity of the multitarget protein-based test was 42.9% for advanced neoplasias compared with 37.3% with standard FIT. Its specificity was similar to that of standard FIT, at 96.6% for advanced neoplasias. 

In a more recent report published in The Lancet Oncology, the team modeled three scenarios comparing the two FIT tests. These scenarios used different cutoff values for a test to be positive for CRC or an advanced lesion.

Overall, the analysis included stool samples from 13,187 patients aged 55-75 years who were in the Netherlands’ national CRC screening program. Stool samples were evaluated with both the multitarget test and the standard FIT, using a positivity cutoff ≥ 47 mcg hemoglobin/g feces. Colonoscopy data were available for only 1270 participants. 

In scenario 1, the multitarget test had a lower threshold for a positive test and consequently identified more precancerous lesions than the standard FIT (828 vs 354, respectively). The multitarget FIT identified a few more CRC cases: Of 29 colonoscopy-confirmed CRC cases, the multitarget FIT identified 26 vs 23 with standard FIT. 

But the multitarget FIT also had more than double the number of false-positives than the standard FIT (347 vs 161, respectively).

Perhaps the most telling comparison occurred in scenario 2, with both tests set at the same low positivity threshold to minimize false-positives.

As expected, the two tests had similar positivity rates for advanced lesions, with the multitarget test correctly identifying 22 of 29 people with CRC, one fewer than the standard test. The protein-based test identified slightly more people with advanced lesions (156 vs 136 with the standard test), leading to a higher sensitivity for advanced lesions. 

Most notably, the protein-based test resulted in fewer false-positives than did the standard test (295 vs 311, respectively) , resulting in a slightly higher specificity.

In this scenario, “a single screening round might not have the biggest impact on cancer incidence and mortality,” the authors said, but the higher detection rate would still accumulate over 20 years of testing. The authors estimated that, under this scenario, substituting the multitarget FIT for the standard test in the Netherlands’ CRC screening program could reduce CRC incidence by 5% and CRC mortality by 4%.

Gerrit Meijer, MD, PhD, a pathologist at the Netherlands Cancer Institute, and colleagues recently launched a company called CRCbioscreen to commercialize this multitarget FIT for large-scale programs. The company›s priority is to develop and validate a clinical-grade test to sell to federal governments with national screening programs, such as those throughout Europe, Australia, and Asia, Dr. Meijer told this news organization. Dr. Meijer expects this process will take about 4 years.

The test will be developed for the US market, but with no nationwide screening program in the United States, future availability will depend on interest from providers and institutions, noted Dr. Meijer, who is also chief scientific officer at CRCbioscreen.

Overall, these three new multitarget stool-based CRC screening tests could help catch more cancers and advanced precancerous lesions. And, if the tests have a high enough specificity, a negative test result could also allow people to forgo screening colonoscopy. 

Still, people with a positive FIT finding would require follow-up colonoscopy, but about 10% of patients decline colonoscopy following an abnormal FIT, Mark A. Lewis, MD, director of gastrointestinal oncology at Intermountain Health in Murray, Utah, told this news organization last year. That means that even if precancerous lesions and CRC are being caught earlier, treatment can’t be started unless people follow through with colonoscopy.

A version of this article appeared on Medscape.com.

Multitarget stool-based tests are showing promise for colorectal cancer (CRC) screening in average-risk individuals and could edge out the current standard fecal immunochemical test (FIT).

These new tests aren’t radical departures from the standard FIT. Like the standard test, the multitarget FIT uses antibodies to test for hemoglobin in stool samples. But these multitarget approaches take the standard FIT a step further by testing for additional DNA, RNA, or protein biomarkers associated with CRC to help improve early detection.

Currently, the US Preventive Services Task Force (USPSTF) recommends two FIT tests — standard FIT and stool FIT-DNA — as well as a third noninvasive CRC screening test, guaiac fecal occult blood test (gFOBT). gFOBT detects heme, a component of hemoglobin, through a chemical reaction.

But both standard FIT and stool FIT-DNA come with caveats. Compared to the standard test, FIT-DNA tends to be better at detecting traces of blood in the stool, and thus can uncover more instances of CRC or other advanced lesions. The flipside is that the DNA test also often leads to more false-positive findings.

In fact, the American College of Physicians does not recommend stool FIT-DNA for screening, citing issues such as cost — more than $600 per test vs about $30 for standard FIT — and the greater likelihood of false-positives compared with both standard FIT and gFOBT.

Given these trade-offs with current noninvasive screening options, developing a FIT option that can improve early detection of CRC and advanced precancerous lesions without increasing false-positives could make a big difference in outcomes. 

Three new noninvasive multitarget tests under investigation — an updated DNA-based test, Cologuard 2.0 (Exact Sciences; Madison, WI); an RNA-based test, ColoSense (Geneoscopy; St Louis, MO); and a protein-based test from CRCbioscreen (Amsterdam, the Netherlands) — may be able to do just that. 
 

Cologuard 2.0: Multitarget Stool DNA-Based Test

An updated version of the stool FIT-DNA is currently under development. Dubbed Next Generation Cologuard, or Cologuard 2.0, this multitarget test detects three novel methylated DNA markers along with fecal hemoglobin.

In a recent trial comparing Cologuard 2.0 vs standard FIT, 20,176 participants aged 40 years or older were screened with Cologuard 2.0 as well as standard FIT before they all also received a colonoscopy. The researchers compared findings with Cologuard 2.0 and standard FIT, which used a positivity cutoff ≥ 20 mcg hemoglobin/g feces. 

The researchers then assessed Cologuard 2.0’s sensitivity (a gauge of how well it detects disease that is truly present) and specificity (a measure of how well a test indicates the absence of disease when no disease is present) compared with standard FIT and the original Cologuard test.

Overall, Cologuard 2.0 demonstrated better sensitivity for CRC than did standard FIT (93.9% vs 67.3%, respectively) and for advanced precancerous lesions (43.4% vs 23.3%). The next-generation test, for instance, identified 92 of 98 participants with colonoscopy-confirmed CRC diagnoses vs 66 cases using standard FIT.

Compared with the original Cologuard, Cologuard 2.0’s sensitivity improved slightly for CRC, from 92% to 93.9%,; for advanced precancerous lesions, from 42% to 43.4%; and for high-grade dysplasia, from 69% to 75%. Specificity also improved with the latest version, from 87% to 90.6%. 

However, Cologuard 2.0’s specificity for advanced neoplasia was worse than that of standard FIT (90.6% vs 94.8%, respectively), which would increase the likelihood of false-positive findings.

Despite its lower specificity compared with standard FIT, Cologuard 2.0 has several advantages. The test can identify more people with CRC and advanced precancerous lesions than the standard test and can lead to fewer false-positives than the original Cologuard test.

Cologuard maker Exact Sciences has submitted trial data to the US Food and Drug Administration (FDA) for approval.
 

Multitarget Stool RNA-Based Test

ColoSense, an RNA-based stool test, looks for eight RNA biomarkers associated with CRC. 

The company says that RNA-based testing has an advantage over DNA biomarker assays, such as the currently marketed Cologuard test, because it isn›t subject to the age-related changes in DNA methylation that can throw off the results from DNA assays. 

Like Cologuard 2.0, Geneoscopy’s Colosense test is under review by the FDA.

The data Geneoscopy submitted to the FDA came from the CRC-PREVENT trial, which included 8920 participants who were screened with both ColoSense and standard FIT before all had a colonoscopy. The participants ranged in age from 45 to 90 years, with 22% between 45 and 50 years old, a population recently added to the USPSTF screening recommendations. 

ColoSense showed higher sensitivity than standard FIT for the presence of CRC (94% vs 78%, respectively) and advanced adenomas (46% vs 29%). In the group aged 45-50 years, the RNA-based test had a sensitivity of 100% for CRC, correctly identifying all five people with colonoscopy-confirmed CRC, and 45% for advanced adenomas.

However, ColoSense was less specific than standard FIT compared with negative colonoscopy findings (88% vs 96%, respectively) and negative findings for advanced lesions or CRC (85.5% vs 94.9%); thus, it was more likely to lead to false-positive results.

Overall, the investigators said ColoSense is comparable to Cologuard — its chief market rival — in terms of sensitivity for CRC and advanced adenomas but has higher sensitivity for colorectal neoplasia in people aged 50 years or younger.
 

Multitarget Protein-Based Test

The multitarget protein-based FIT uses antibodies to test for two additional proteins: calprotectin, an inflammatory marker associated with CRC, and serpin family F member 2, a protease inhibitor thought to be upregulated in colon cancer. 

A 2021 study of 1284 patients found that the sensitivity of the multitarget protein-based test was 42.9% for advanced neoplasias compared with 37.3% with standard FIT. Its specificity was similar to that of standard FIT, at 96.6% for advanced neoplasias. 

In a more recent report published in The Lancet Oncology, the team modeled three scenarios comparing the two FIT tests. These scenarios used different cutoff values for a test to be positive for CRC or an advanced lesion.

Overall, the analysis included stool samples from 13,187 patients aged 55-75 years who were in the Netherlands’ national CRC screening program. Stool samples were evaluated with both the multitarget test and the standard FIT, using a positivity cutoff ≥ 47 mcg hemoglobin/g feces. Colonoscopy data were available for only 1270 participants. 

In scenario 1, the multitarget test had a lower threshold for a positive test and consequently identified more precancerous lesions than the standard FIT (828 vs 354, respectively). The multitarget FIT identified a few more CRC cases: Of 29 colonoscopy-confirmed CRC cases, the multitarget FIT identified 26 vs 23 with standard FIT. 

But the multitarget FIT also had more than double the number of false-positives than the standard FIT (347 vs 161, respectively).

Perhaps the most telling comparison occurred in scenario 2, with both tests set at the same low positivity threshold to minimize false-positives.

As expected, the two tests had similar positivity rates for advanced lesions, with the multitarget test correctly identifying 22 of 29 people with CRC, one fewer than the standard test. The protein-based test identified slightly more people with advanced lesions (156 vs 136 with the standard test), leading to a higher sensitivity for advanced lesions. 

Most notably, the protein-based test resulted in fewer false-positives than did the standard test (295 vs 311, respectively) , resulting in a slightly higher specificity.

In this scenario, “a single screening round might not have the biggest impact on cancer incidence and mortality,” the authors said, but the higher detection rate would still accumulate over 20 years of testing. The authors estimated that, under this scenario, substituting the multitarget FIT for the standard test in the Netherlands’ CRC screening program could reduce CRC incidence by 5% and CRC mortality by 4%.

Gerrit Meijer, MD, PhD, a pathologist at the Netherlands Cancer Institute, and colleagues recently launched a company called CRCbioscreen to commercialize this multitarget FIT for large-scale programs. The company›s priority is to develop and validate a clinical-grade test to sell to federal governments with national screening programs, such as those throughout Europe, Australia, and Asia, Dr. Meijer told this news organization. Dr. Meijer expects this process will take about 4 years.

The test will be developed for the US market, but with no nationwide screening program in the United States, future availability will depend on interest from providers and institutions, noted Dr. Meijer, who is also chief scientific officer at CRCbioscreen.

Overall, these three new multitarget stool-based CRC screening tests could help catch more cancers and advanced precancerous lesions. And, if the tests have a high enough specificity, a negative test result could also allow people to forgo screening colonoscopy. 

Still, people with a positive FIT finding would require follow-up colonoscopy, but about 10% of patients decline colonoscopy following an abnormal FIT, Mark A. Lewis, MD, director of gastrointestinal oncology at Intermountain Health in Murray, Utah, told this news organization last year. That means that even if precancerous lesions and CRC are being caught earlier, treatment can’t be started unless people follow through with colonoscopy.

A version of this article appeared on Medscape.com.

A newly developed quality performance measure that tracks completion of colorectal cancer (CRC) screening with a colonoscopy within 6 months of an abnormal stool-based screening test (SBT) in adults could help address high rates of incomplete CRC screening, the developers said.

As part of their work, the researchers conducted a retrospective study of 20,581 adults aged 50-75 years from 38 health systems that showed that fewer than half (48%) had a follow-up colonoscopy within 180 days of an initial abnormal SBT for CRC.

“The low follow-up rates to an abnormal SBT were initially surprising,” first author Elizabeth L. Ciemins, PhD, MPH, MA, Research and Analytics, American Medical Group Association (AMGA), Alexandria, Virginia, told this news organization.

“However, once we interviewed clinicians and learned that this was not a measure they were tracking, along with their own incorrect assumptions of a much higher follow-up rate, the low rates made sense. As is commonly said, ‘you can’t change what you don’t measure,’” she said.

The CRC screening completion measure the researchers propose “builds on and addresses an important shortcoming in an existing measure and will help ensure complete screening for CRC,” they noted in their JAMA Network Open paper.

The key elements of the follow-up measure are the date and result of a SBT and the date of the follow-up colonoscopy — if it occurred, Dr. Ciemins explained.

“Currently, health systems are not consistently tracking this measure, but they have the data elements to do so, especially if they are doing colonoscopies in-house,” she said.

Field testing showed that use of this new measure is “feasible, valid, and reliable,” the authors said. Dr. Ciemins believed this CRC screening completion measure could be widely implemented.

“Three AMGA member health systems feasibility tested the data elements and found that they could reliably abstract the required elements from electronic health records (EHRs),” she told this news organization.

The researchers are currently testing the measure among 20 AMGA member health systems, that are submitting quarterly data on a version of the specified measure.

“Advancing this measure as a quality performance measure could significantly increase the early detection of CRC, thereby improving health and ultimately saving lives,” the authors concluded in their paper.

The Right Direction, But Questions Remain

The coauthors of a linked commentary said this research highlights the “suboptimal” rates of a timely follow-up colonoscopy after positive SBT results. They applauded the authors for “focusing attention on a meaningful approach to measuring high-quality CRC screening and providing guidance for standardized measurement.”

However, several questions arise from this study, “including whether 6 months is the ideal interval for colonoscopy completion after a positive SBT result, where this measure fits in the context of existing CRC screening measures, and how to implement it in practice,” Jennifer K. Maratt, MD, with Indiana University School of Medicine, Indianapolis, and coauthors wrote.

“This measure alone does not address all the gaps in the screening process, nor does it address barriers to colonoscopy completion, but it points us in the right direction for measuring the success of screening programs,” Dr. Maratt and her colleagues added.

The study was supported by a grant from the AARP. The authors and editorial writers had no relevant disclosures.

A version of this article appeared on Medscape.com.

A newly developed quality performance measure that tracks completion of colorectal cancer (CRC) screening with a colonoscopy within 6 months of an abnormal stool-based screening test (SBT) in adults could help address high rates of incomplete CRC screening, the developers said.

As part of their work, the researchers conducted a retrospective study of 20,581 adults aged 50-75 years from 38 health systems that showed that fewer than half (48%) had a follow-up colonoscopy within 180 days of an initial abnormal SBT for CRC.

“The low follow-up rates to an abnormal SBT were initially surprising,” first author Elizabeth L. Ciemins, PhD, MPH, MA, Research and Analytics, American Medical Group Association (AMGA), Alexandria, Virginia, told this news organization.

“However, once we interviewed clinicians and learned that this was not a measure they were tracking, along with their own incorrect assumptions of a much higher follow-up rate, the low rates made sense. As is commonly said, ‘you can’t change what you don’t measure,’” she said.

The CRC screening completion measure the researchers propose “builds on and addresses an important shortcoming in an existing measure and will help ensure complete screening for CRC,” they noted in their JAMA Network Open paper.

The key elements of the follow-up measure are the date and result of a SBT and the date of the follow-up colonoscopy — if it occurred, Dr. Ciemins explained.

“Currently, health systems are not consistently tracking this measure, but they have the data elements to do so, especially if they are doing colonoscopies in-house,” she said.

Field testing showed that use of this new measure is “feasible, valid, and reliable,” the authors said. Dr. Ciemins believed this CRC screening completion measure could be widely implemented.

“Three AMGA member health systems feasibility tested the data elements and found that they could reliably abstract the required elements from electronic health records (EHRs),” she told this news organization.

The researchers are currently testing the measure among 20 AMGA member health systems, that are submitting quarterly data on a version of the specified measure.

“Advancing this measure as a quality performance measure could significantly increase the early detection of CRC, thereby improving health and ultimately saving lives,” the authors concluded in their paper.

The Right Direction, But Questions Remain

The coauthors of a linked commentary said this research highlights the “suboptimal” rates of a timely follow-up colonoscopy after positive SBT results. They applauded the authors for “focusing attention on a meaningful approach to measuring high-quality CRC screening and providing guidance for standardized measurement.”

However, several questions arise from this study, “including whether 6 months is the ideal interval for colonoscopy completion after a positive SBT result, where this measure fits in the context of existing CRC screening measures, and how to implement it in practice,” Jennifer K. Maratt, MD, with Indiana University School of Medicine, Indianapolis, and coauthors wrote.

“This measure alone does not address all the gaps in the screening process, nor does it address barriers to colonoscopy completion, but it points us in the right direction for measuring the success of screening programs,” Dr. Maratt and her colleagues added.

The study was supported by a grant from the AARP. The authors and editorial writers had no relevant disclosures.

A version of this article appeared on Medscape.com.

A newly developed quality performance measure that tracks completion of colorectal cancer (CRC) screening with a colonoscopy within 6 months of an abnormal stool-based screening test (SBT) in adults could help address high rates of incomplete CRC screening, the developers said.

As part of their work, the researchers conducted a retrospective study of 20,581 adults aged 50-75 years from 38 health systems that showed that fewer than half (48%) had a follow-up colonoscopy within 180 days of an initial abnormal SBT for CRC.

“The low follow-up rates to an abnormal SBT were initially surprising,” first author Elizabeth L. Ciemins, PhD, MPH, MA, Research and Analytics, American Medical Group Association (AMGA), Alexandria, Virginia, told this news organization.

“However, once we interviewed clinicians and learned that this was not a measure they were tracking, along with their own incorrect assumptions of a much higher follow-up rate, the low rates made sense. As is commonly said, ‘you can’t change what you don’t measure,’” she said.

The CRC screening completion measure the researchers propose “builds on and addresses an important shortcoming in an existing measure and will help ensure complete screening for CRC,” they noted in their JAMA Network Open paper.

The key elements of the follow-up measure are the date and result of a SBT and the date of the follow-up colonoscopy — if it occurred, Dr. Ciemins explained.

“Currently, health systems are not consistently tracking this measure, but they have the data elements to do so, especially if they are doing colonoscopies in-house,” she said.

Field testing showed that use of this new measure is “feasible, valid, and reliable,” the authors said. Dr. Ciemins believed this CRC screening completion measure could be widely implemented.

“Three AMGA member health systems feasibility tested the data elements and found that they could reliably abstract the required elements from electronic health records (EHRs),” she told this news organization.

The researchers are currently testing the measure among 20 AMGA member health systems, that are submitting quarterly data on a version of the specified measure.

“Advancing this measure as a quality performance measure could significantly increase the early detection of CRC, thereby improving health and ultimately saving lives,” the authors concluded in their paper.

The Right Direction, But Questions Remain

The coauthors of a linked commentary said this research highlights the “suboptimal” rates of a timely follow-up colonoscopy after positive SBT results. They applauded the authors for “focusing attention on a meaningful approach to measuring high-quality CRC screening and providing guidance for standardized measurement.”

However, several questions arise from this study, “including whether 6 months is the ideal interval for colonoscopy completion after a positive SBT result, where this measure fits in the context of existing CRC screening measures, and how to implement it in practice,” Jennifer K. Maratt, MD, with Indiana University School of Medicine, Indianapolis, and coauthors wrote.

“This measure alone does not address all the gaps in the screening process, nor does it address barriers to colonoscopy completion, but it points us in the right direction for measuring the success of screening programs,” Dr. Maratt and her colleagues added.

The study was supported by a grant from the AARP. The authors and editorial writers had no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Being positive for Helicobacter pylori is associated with a higher risk for colorectal cancer (CRC) incidence and CRC mortality, new data show; however, a 2-week course of antibiotics to eliminate the bacterial infection can reduce the risk of developing and dying from CRC.

METHODOLOGY:

• H pylori is a known cause of peptic ulcers and stomach cancer and has been classified as a group I carcinogen by the World Health Organization›s International Agency for Research on Cancer.
• Studies showed that H pylori increases the risk for gastric cancer and may increase the risk for CRC, but evidence supporting the CRC connection remains inconsistent.
• To investigate a possible H pylori-CRC link, investigators reviewed CRC incidence and mortality in a nationwide cohort of 812,736 veterans tested for H pylori at Veterans Health Administration facilities; of the 205,178 (25.2%) who tested positive for H pylori, 134,417 (34%) were treated.
• Patients were followed from their first H pylori test, and researchers tracked subsequent CRC diagnoses as well as CRC-related and non-CRC–related deaths.

TAKEAWAY:

• H pylori infection was associated with an 18% higher risk for CRC (adjusted hazard ratio [aHR], 1.18) and a 12% higher risk for CRC mortality (aHR, 1.12).
• Untreated patients had a 23% higher risk for CRC (aHR, 1.23) and a 40% higher risk for CRC mortality (aHR, 1.40) than treated individuals.
• Over the 15-year follow-up, receiving treatment for H pylori infection vs no treatment was associated with a lower risk of developing and dying from CRC (absolute risk reduction, 0.23%-0.35%). For context, among individuals receiving a screening colonoscopy, the invasive test was associated with a 0.84%-1.22% absolute risk reduction in CRC incidence and a 0.15-0.30% absolute risk reduction in CRC mortality.
• Excluding patients diagnosed with CRC within a year of H pylori testing did not change the associations in the study.

IN PRACTICE:

“We would like to highlight the potentially exciting clinical implications of these findings,” the authors of an accompanying editorial wrote. “Although the mechanistic connection between H pylori and colorectal cancer is not fully resolved,” the finding that eliminating H pylori “could reduce both gastric and colorectal cancers is incredibly potent and should be considered in clinical care for individuals at high risk for GI [gastrointestinal] cancers.”

SOURCE:

The work, led by Shailja C. Shah, MD, of the University of California San Diego, was published in the Journal of Clinical Oncology, alongside the accompanying editorial by Julia Butt, PhD, of the German Cancer Research Center, Heidelberg, Germany, and Meira Epplein, PhD, of Duke University in Durham, North Carolina.

LIMITATIONS:

The study was limited to US veterans, which means generalizability to other populations needed to be confirmed. There may have been differences in CRC risk factors between treated and untreated patients.

DISCLOSURES:

The work was funded by the Veterans Health Administration, the National Cancer Institute, and others. Investigators reported ties to numerous companies, including AstraZeneca, Novartis, Guardant Health, and Medscape Medical News, publisher of this article. The editorialists had no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Being positive for Helicobacter pylori is associated with a higher risk for colorectal cancer (CRC) incidence and CRC mortality, new data show; however, a 2-week course of antibiotics to eliminate the bacterial infection can reduce the risk of developing and dying from CRC.

METHODOLOGY:

• H pylori is a known cause of peptic ulcers and stomach cancer and has been classified as a group I carcinogen by the World Health Organization›s International Agency for Research on Cancer.
• Studies showed that H pylori increases the risk for gastric cancer and may increase the risk for CRC, but evidence supporting the CRC connection remains inconsistent.
• To investigate a possible H pylori-CRC link, investigators reviewed CRC incidence and mortality in a nationwide cohort of 812,736 veterans tested for H pylori at Veterans Health Administration facilities; of the 205,178 (25.2%) who tested positive for H pylori, 134,417 (34%) were treated.
• Patients were followed from their first H pylori test, and researchers tracked subsequent CRC diagnoses as well as CRC-related and non-CRC–related deaths.

TAKEAWAY:

• H pylori infection was associated with an 18% higher risk for CRC (adjusted hazard ratio [aHR], 1.18) and a 12% higher risk for CRC mortality (aHR, 1.12).
• Untreated patients had a 23% higher risk for CRC (aHR, 1.23) and a 40% higher risk for CRC mortality (aHR, 1.40) than treated individuals.
• Over the 15-year follow-up, receiving treatment for H pylori infection vs no treatment was associated with a lower risk of developing and dying from CRC (absolute risk reduction, 0.23%-0.35%). For context, among individuals receiving a screening colonoscopy, the invasive test was associated with a 0.84%-1.22% absolute risk reduction in CRC incidence and a 0.15-0.30% absolute risk reduction in CRC mortality.
• Excluding patients diagnosed with CRC within a year of H pylori testing did not change the associations in the study.

IN PRACTICE:

“We would like to highlight the potentially exciting clinical implications of these findings,” the authors of an accompanying editorial wrote. “Although the mechanistic connection between H pylori and colorectal cancer is not fully resolved,” the finding that eliminating H pylori “could reduce both gastric and colorectal cancers is incredibly potent and should be considered in clinical care for individuals at high risk for GI [gastrointestinal] cancers.”

SOURCE:

The work, led by Shailja C. Shah, MD, of the University of California San Diego, was published in the Journal of Clinical Oncology, alongside the accompanying editorial by Julia Butt, PhD, of the German Cancer Research Center, Heidelberg, Germany, and Meira Epplein, PhD, of Duke University in Durham, North Carolina.

LIMITATIONS:

The study was limited to US veterans, which means generalizability to other populations needed to be confirmed. There may have been differences in CRC risk factors between treated and untreated patients.

DISCLOSURES:

The work was funded by the Veterans Health Administration, the National Cancer Institute, and others. Investigators reported ties to numerous companies, including AstraZeneca, Novartis, Guardant Health, and Medscape Medical News, publisher of this article. The editorialists had no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Being positive for Helicobacter pylori is associated with a higher risk for colorectal cancer (CRC) incidence and CRC mortality, new data show; however, a 2-week course of antibiotics to eliminate the bacterial infection can reduce the risk of developing and dying from CRC.

METHODOLOGY:

• H pylori is a known cause of peptic ulcers and stomach cancer and has been classified as a group I carcinogen by the World Health Organization›s International Agency for Research on Cancer.
• Studies showed that H pylori increases the risk for gastric cancer and may increase the risk for CRC, but evidence supporting the CRC connection remains inconsistent.
• To investigate a possible H pylori-CRC link, investigators reviewed CRC incidence and mortality in a nationwide cohort of 812,736 veterans tested for H pylori at Veterans Health Administration facilities; of the 205,178 (25.2%) who tested positive for H pylori, 134,417 (34%) were treated.
• Patients were followed from their first H pylori test, and researchers tracked subsequent CRC diagnoses as well as CRC-related and non-CRC–related deaths.

TAKEAWAY:

• H pylori infection was associated with an 18% higher risk for CRC (adjusted hazard ratio [aHR], 1.18) and a 12% higher risk for CRC mortality (aHR, 1.12).
• Untreated patients had a 23% higher risk for CRC (aHR, 1.23) and a 40% higher risk for CRC mortality (aHR, 1.40) than treated individuals.
• Over the 15-year follow-up, receiving treatment for H pylori infection vs no treatment was associated with a lower risk of developing and dying from CRC (absolute risk reduction, 0.23%-0.35%). For context, among individuals receiving a screening colonoscopy, the invasive test was associated with a 0.84%-1.22% absolute risk reduction in CRC incidence and a 0.15-0.30% absolute risk reduction in CRC mortality.
• Excluding patients diagnosed with CRC within a year of H pylori testing did not change the associations in the study.

IN PRACTICE:

“We would like to highlight the potentially exciting clinical implications of these findings,” the authors of an accompanying editorial wrote. “Although the mechanistic connection between H pylori and colorectal cancer is not fully resolved,” the finding that eliminating H pylori “could reduce both gastric and colorectal cancers is incredibly potent and should be considered in clinical care for individuals at high risk for GI [gastrointestinal] cancers.”

SOURCE:

The work, led by Shailja C. Shah, MD, of the University of California San Diego, was published in the Journal of Clinical Oncology, alongside the accompanying editorial by Julia Butt, PhD, of the German Cancer Research Center, Heidelberg, Germany, and Meira Epplein, PhD, of Duke University in Durham, North Carolina.

LIMITATIONS:

The study was limited to US veterans, which means generalizability to other populations needed to be confirmed. There may have been differences in CRC risk factors between treated and untreated patients.

DISCLOSURES:

The work was funded by the Veterans Health Administration, the National Cancer Institute, and others. Investigators reported ties to numerous companies, including AstraZeneca, Novartis, Guardant Health, and Medscape Medical News, publisher of this article. The editorialists had no disclosures.

A version of this article appeared on Medscape.com.

Healthcare providers hold wide-ranging opinions about prescribing opioids for chronic cancer pain, and many are haunted by the conflicting factors driving their views, from legal concerns to threats of violence, say the authors of new research.

These findings suggest that evidence-based, systematic guidance is needed to steer opioid usage in cancer survivorship, wrote lead author Hailey W. Bulls, PhD, of the University of Pittsburgh, and colleagues.

“Prescription opioids are considered the standard of care to treat moderate to severe cancer pain during active treatment, yet guidance in the posttreatment survivorship phase is much less clear,” the investigators wrote. “Existing clinical resources recognize that opioid prescribing in survivorship is complex and nuanced and that the relative benefits and risks in this population are not fully understood.”
 

Who Should Manage Chronic Cancer Pain?

Despite the knowledge gap, survivors are typically excluded from long-term opioid use studies, leaving providers in a largely data-free zone. Simultaneously, patients who had been receiving focused care during their cancer treatment find themselves with an ill-defined health care team.

“Without a clear transition of care, survivors may seek pain management services from a variety of specialties, including oncologists, palliative care clinicians, primary care clinicians, and pain management specialists,” the investigators wrote. “However, many clinicians may view pain management to be outside of their skill set and may not be well equipped to handle opioid continuation or deprescribing [or] to manage the potential consequences of long‐term opioid use like side effects, misuse, and/or opioid use disorder.”
 

What Factors Guide Opioid Prescribing Practices for Chronic Cancer Pain?

To learn more about prescribing practices in this setting, Dr. Bulls and colleagues conducted qualitative interviews with 20 providers representing four specialties: oncology (n = 5), palliative care (n = 8), primary care (n = 5), and pain management (n = 2). Eighteen of these participants were physicians and two were advanced practice providers. Average time in clinical practice was about 16 years.

These interviews yielded three themes.

First, no “medical home” exists for chronic pain management in cancer survivors.

“Although clinicians generally agreed that minimizing the role of opioids in chronic pain management in cancer survivors was desirable, they described a lack of common treatment protocols to guide pain management in survivorship,” the investigators wrote.

Second, the interviews revealed that prescribing strategies are partly driven by peer pressure, sometimes leading to tension between providers and feelings of self-doubt.

“I feel like there’s been this weird judgment thing that’s happened [to] the prescribers,” one primary care provider said during the interview. “Because, when I trained … pain was a vital sign, and we were supposed to treat pain, and now I feel like we’re all being judged for that.”

The third theme revolved around fear of consequences resulting from prescribing practices, including fears of violent repercussions.

“You may not know, but pain specialists have been shot in this country for [refusing to prescribe opioids],” one pain management specialist said during the interview. “There’s been a number of shootings of pain specialists who would not prescribe opioids. So, I mean, there’s real issues of violence.”

Meanwhile, a palliative care provider described legal pressure from the opposite direction:

“I think there’s a lot of fear of litigiousness … and loss of licenses. That sort of makes them pressure us into not prescribing opioids or sticking with a certain number per day that might not be therapeutic for a patient.”

Reflecting on these themes, the investigators identified “a fundamental uncertainty in survivorship pain management.”
 

What Strategies Might Improve Opioid Prescribing Practices for Chronic Cancer Pain?

After sharing their attitudes about prescribing opioids for chronic cancer pain, the clinicians were asked for suggestions to improve the situation.

They offered four main suggestions: create relevant guidelines, increase education and access to pain management options for clinicians, increase interdisciplinary communication across medical subspecialties, and promote multidisciplinary care in the survivorship setting.

Dr. Bulls and colleagues supported these strategies in their concluding remarks and called for more research.

This study was supported by the National Institute of Drug Abuse, the National Institutes of Health, the National Center for Advancing Translational Sciences, and the National Cancer Institute. The investigators disclosed relationships with Arcadia Health Solutions and Biomotivate.

Healthcare providers hold wide-ranging opinions about prescribing opioids for chronic cancer pain, and many are haunted by the conflicting factors driving their views, from legal concerns to threats of violence, say the authors of new research.

These findings suggest that evidence-based, systematic guidance is needed to steer opioid usage in cancer survivorship, wrote lead author Hailey W. Bulls, PhD, of the University of Pittsburgh, and colleagues.

“Prescription opioids are considered the standard of care to treat moderate to severe cancer pain during active treatment, yet guidance in the posttreatment survivorship phase is much less clear,” the investigators wrote. “Existing clinical resources recognize that opioid prescribing in survivorship is complex and nuanced and that the relative benefits and risks in this population are not fully understood.”
 

Who Should Manage Chronic Cancer Pain?

Despite the knowledge gap, survivors are typically excluded from long-term opioid use studies, leaving providers in a largely data-free zone. Simultaneously, patients who had been receiving focused care during their cancer treatment find themselves with an ill-defined health care team.

“Without a clear transition of care, survivors may seek pain management services from a variety of specialties, including oncologists, palliative care clinicians, primary care clinicians, and pain management specialists,” the investigators wrote. “However, many clinicians may view pain management to be outside of their skill set and may not be well equipped to handle opioid continuation or deprescribing [or] to manage the potential consequences of long‐term opioid use like side effects, misuse, and/or opioid use disorder.”
 

What Factors Guide Opioid Prescribing Practices for Chronic Cancer Pain?

To learn more about prescribing practices in this setting, Dr. Bulls and colleagues conducted qualitative interviews with 20 providers representing four specialties: oncology (n = 5), palliative care (n = 8), primary care (n = 5), and pain management (n = 2). Eighteen of these participants were physicians and two were advanced practice providers. Average time in clinical practice was about 16 years.

These interviews yielded three themes.

First, no “medical home” exists for chronic pain management in cancer survivors.

“Although clinicians generally agreed that minimizing the role of opioids in chronic pain management in cancer survivors was desirable, they described a lack of common treatment protocols to guide pain management in survivorship,” the investigators wrote.

Second, the interviews revealed that prescribing strategies are partly driven by peer pressure, sometimes leading to tension between providers and feelings of self-doubt.

“I feel like there’s been this weird judgment thing that’s happened [to] the prescribers,” one primary care provider said during the interview. “Because, when I trained … pain was a vital sign, and we were supposed to treat pain, and now I feel like we’re all being judged for that.”

The third theme revolved around fear of consequences resulting from prescribing practices, including fears of violent repercussions.

“You may not know, but pain specialists have been shot in this country for [refusing to prescribe opioids],” one pain management specialist said during the interview. “There’s been a number of shootings of pain specialists who would not prescribe opioids. So, I mean, there’s real issues of violence.”

Meanwhile, a palliative care provider described legal pressure from the opposite direction:

“I think there’s a lot of fear of litigiousness … and loss of licenses. That sort of makes them pressure us into not prescribing opioids or sticking with a certain number per day that might not be therapeutic for a patient.”

Reflecting on these themes, the investigators identified “a fundamental uncertainty in survivorship pain management.”
 

What Strategies Might Improve Opioid Prescribing Practices for Chronic Cancer Pain?

After sharing their attitudes about prescribing opioids for chronic cancer pain, the clinicians were asked for suggestions to improve the situation.

They offered four main suggestions: create relevant guidelines, increase education and access to pain management options for clinicians, increase interdisciplinary communication across medical subspecialties, and promote multidisciplinary care in the survivorship setting.

Dr. Bulls and colleagues supported these strategies in their concluding remarks and called for more research.

This study was supported by the National Institute of Drug Abuse, the National Institutes of Health, the National Center for Advancing Translational Sciences, and the National Cancer Institute. The investigators disclosed relationships with Arcadia Health Solutions and Biomotivate.

Healthcare providers hold wide-ranging opinions about prescribing opioids for chronic cancer pain, and many are haunted by the conflicting factors driving their views, from legal concerns to threats of violence, say the authors of new research.

These findings suggest that evidence-based, systematic guidance is needed to steer opioid usage in cancer survivorship, wrote lead author Hailey W. Bulls, PhD, of the University of Pittsburgh, and colleagues.

“Prescription opioids are considered the standard of care to treat moderate to severe cancer pain during active treatment, yet guidance in the posttreatment survivorship phase is much less clear,” the investigators wrote. “Existing clinical resources recognize that opioid prescribing in survivorship is complex and nuanced and that the relative benefits and risks in this population are not fully understood.”
 

Who Should Manage Chronic Cancer Pain?

Despite the knowledge gap, survivors are typically excluded from long-term opioid use studies, leaving providers in a largely data-free zone. Simultaneously, patients who had been receiving focused care during their cancer treatment find themselves with an ill-defined health care team.

“Without a clear transition of care, survivors may seek pain management services from a variety of specialties, including oncologists, palliative care clinicians, primary care clinicians, and pain management specialists,” the investigators wrote. “However, many clinicians may view pain management to be outside of their skill set and may not be well equipped to handle opioid continuation or deprescribing [or] to manage the potential consequences of long‐term opioid use like side effects, misuse, and/or opioid use disorder.”
 

What Factors Guide Opioid Prescribing Practices for Chronic Cancer Pain?

To learn more about prescribing practices in this setting, Dr. Bulls and colleagues conducted qualitative interviews with 20 providers representing four specialties: oncology (n = 5), palliative care (n = 8), primary care (n = 5), and pain management (n = 2). Eighteen of these participants were physicians and two were advanced practice providers. Average time in clinical practice was about 16 years.

These interviews yielded three themes.

First, no “medical home” exists for chronic pain management in cancer survivors.

“Although clinicians generally agreed that minimizing the role of opioids in chronic pain management in cancer survivors was desirable, they described a lack of common treatment protocols to guide pain management in survivorship,” the investigators wrote.

Second, the interviews revealed that prescribing strategies are partly driven by peer pressure, sometimes leading to tension between providers and feelings of self-doubt.

“I feel like there’s been this weird judgment thing that’s happened [to] the prescribers,” one primary care provider said during the interview. “Because, when I trained … pain was a vital sign, and we were supposed to treat pain, and now I feel like we’re all being judged for that.”

The third theme revolved around fear of consequences resulting from prescribing practices, including fears of violent repercussions.

“You may not know, but pain specialists have been shot in this country for [refusing to prescribe opioids],” one pain management specialist said during the interview. “There’s been a number of shootings of pain specialists who would not prescribe opioids. So, I mean, there’s real issues of violence.”

Meanwhile, a palliative care provider described legal pressure from the opposite direction:

“I think there’s a lot of fear of litigiousness … and loss of licenses. That sort of makes them pressure us into not prescribing opioids or sticking with a certain number per day that might not be therapeutic for a patient.”

Reflecting on these themes, the investigators identified “a fundamental uncertainty in survivorship pain management.”
 

What Strategies Might Improve Opioid Prescribing Practices for Chronic Cancer Pain?

After sharing their attitudes about prescribing opioids for chronic cancer pain, the clinicians were asked for suggestions to improve the situation.

They offered four main suggestions: create relevant guidelines, increase education and access to pain management options for clinicians, increase interdisciplinary communication across medical subspecialties, and promote multidisciplinary care in the survivorship setting.

Dr. Bulls and colleagues supported these strategies in their concluding remarks and called for more research.

This study was supported by the National Institute of Drug Abuse, the National Institutes of Health, the National Center for Advancing Translational Sciences, and the National Cancer Institute. The investigators disclosed relationships with Arcadia Health Solutions and Biomotivate.