Howard Wolinsky

Artera, the Los Altos, California–based developer of tools to diagnose cancer, has launched the first artificial intelligence (AI) test to guide patients in making informed decisions between active surveillance and active treatment based on an analysis of digital pathology images.

Trevor Royce, MD, MPH, senior medical director of Artera, said the new version of the ArteraAI Prostate Test helps patients with low-risk (Grade Group 1/Gleason 6) to favorable intermediate-risk (Grade Group 2/Gleason 3+4) prostate cancer choose between treatment or active surveillance.

The test estimates how a patient’s cancer may progress and predicts the benefit of treatment for localized prostate cancer. 

“The prognostic performance of the test has now been validated in a diverse cohort of patients, including those who have undergone active surveillance, radiation therapy, or had a radical prostatectomy,” said Dr. Royce, a faculty member in radiation oncology at Wake Forest University School of Medicine in Winston-Salem, North Carolina. “The prognostic risk result reflects the patient’s prognosis regardless of the treatment path chosen.”

Dr. Royce said the new test predicts the risk for developing distant metastasis in 10 years. For the population considering active surveillance, it also can predict the likelihood their cancer will show more aggressive features. The test does not make a clinical recommendation, he added.

“Ultimately, that’s a very personal decision between the patient and their physician, and we view it as supporting that decision-making process,” he said.

The test is available in all states but New York and California, where the company is now, in discussions with regulators for approval, according to Dr. Royce. He said the company is in discussion with private insurers to set reimbursement and payment rates. In January 2024, Medicare set a payment rate of $700 for the AI test, which carries no out-of-pocket costs for patients. 

The first indication for the test was for localized prostate cancer, prognosticating the risk for distant metastases and death from prostate cancer. It can also predict if an individual will benefit from androgen deprivation therapy (ADT). Dr. Royce said up to 60% of patients with intermediate risk prostate cancer now can avoid ADT and its serious side effects, such as brain fog, weight gain, and reduction in muscle mass.

In March, the National Comprehensive Cancer Network, an alliance of 33 cancer centers included Artera as the first AI test in its Clinical Practice Guidelines in Oncology.

Dr. Royce said active surveillance is a new application of the test. The test was initially developed on a foundational study of almost 22,000 pathology slides from nearly 7000 patients published in npj Digital Medicine in 2022.

Todd Morgan, MD, chief of the Division of Urologic Oncology at the University of Michigan in Ann Arbor, and coauthor of the foundational study, said the AI test adds another layer of data to making clinical decisions for lower-risk patients.

“The technology is a big deal. The ability to use digital images to make accurate prognostic estimates is pretty remarkable, and this is the first test in any disease site to do this,” Dr. Morgan said. “Ultimately, this means tests may someday be performed by just sending images rather than sending actual tissue to an outside laboratory. Is the AI test dramatically more accurate than the genomic platforms? That’s TBD [to be determined].”

Dr. Royce said Artera is now working on a version of its test to inform men with higher-risk prostate cancer how long ADT should last and what the prognosis is for patients who have undergone prostatectomy based on their surgical specimen. The current test uses samples from the prostate biopsy, which are processed in a central lab. 

Dr. Royce said the company would like to eventually perform the test using digital images of pathology slides only.

Dr. Morgan reported no conflicts of interest.
 

A version of this article first appeared on Medscape.com.

Artera, the Los Altos, California–based developer of tools to diagnose cancer, has launched the first artificial intelligence (AI) test to guide patients in making informed decisions between active surveillance and active treatment based on an analysis of digital pathology images.

Trevor Royce, MD, MPH, senior medical director of Artera, said the new version of the ArteraAI Prostate Test helps patients with low-risk (Grade Group 1/Gleason 6) to favorable intermediate-risk (Grade Group 2/Gleason 3+4) prostate cancer choose between treatment or active surveillance.

The test estimates how a patient’s cancer may progress and predicts the benefit of treatment for localized prostate cancer. 

“The prognostic performance of the test has now been validated in a diverse cohort of patients, including those who have undergone active surveillance, radiation therapy, or had a radical prostatectomy,” said Dr. Royce, a faculty member in radiation oncology at Wake Forest University School of Medicine in Winston-Salem, North Carolina. “The prognostic risk result reflects the patient’s prognosis regardless of the treatment path chosen.”

Dr. Royce said the new test predicts the risk for developing distant metastasis in 10 years. For the population considering active surveillance, it also can predict the likelihood their cancer will show more aggressive features. The test does not make a clinical recommendation, he added.

“Ultimately, that’s a very personal decision between the patient and their physician, and we view it as supporting that decision-making process,” he said.

The test is available in all states but New York and California, where the company is now, in discussions with regulators for approval, according to Dr. Royce. He said the company is in discussion with private insurers to set reimbursement and payment rates. In January 2024, Medicare set a payment rate of $700 for the AI test, which carries no out-of-pocket costs for patients. 

The first indication for the test was for localized prostate cancer, prognosticating the risk for distant metastases and death from prostate cancer. It can also predict if an individual will benefit from androgen deprivation therapy (ADT). Dr. Royce said up to 60% of patients with intermediate risk prostate cancer now can avoid ADT and its serious side effects, such as brain fog, weight gain, and reduction in muscle mass.

In March, the National Comprehensive Cancer Network, an alliance of 33 cancer centers included Artera as the first AI test in its Clinical Practice Guidelines in Oncology.

Dr. Royce said active surveillance is a new application of the test. The test was initially developed on a foundational study of almost 22,000 pathology slides from nearly 7000 patients published in npj Digital Medicine in 2022.

Todd Morgan, MD, chief of the Division of Urologic Oncology at the University of Michigan in Ann Arbor, and coauthor of the foundational study, said the AI test adds another layer of data to making clinical decisions for lower-risk patients.

“The technology is a big deal. The ability to use digital images to make accurate prognostic estimates is pretty remarkable, and this is the first test in any disease site to do this,” Dr. Morgan said. “Ultimately, this means tests may someday be performed by just sending images rather than sending actual tissue to an outside laboratory. Is the AI test dramatically more accurate than the genomic platforms? That’s TBD [to be determined].”

Dr. Royce said Artera is now working on a version of its test to inform men with higher-risk prostate cancer how long ADT should last and what the prognosis is for patients who have undergone prostatectomy based on their surgical specimen. The current test uses samples from the prostate biopsy, which are processed in a central lab. 

Dr. Royce said the company would like to eventually perform the test using digital images of pathology slides only.

Dr. Morgan reported no conflicts of interest.
 

A version of this article first appeared on Medscape.com.

Artera, the Los Altos, California–based developer of tools to diagnose cancer, has launched the first artificial intelligence (AI) test to guide patients in making informed decisions between active surveillance and active treatment based on an analysis of digital pathology images.

Trevor Royce, MD, MPH, senior medical director of Artera, said the new version of the ArteraAI Prostate Test helps patients with low-risk (Grade Group 1/Gleason 6) to favorable intermediate-risk (Grade Group 2/Gleason 3+4) prostate cancer choose between treatment or active surveillance.

The test estimates how a patient’s cancer may progress and predicts the benefit of treatment for localized prostate cancer. 

“The prognostic performance of the test has now been validated in a diverse cohort of patients, including those who have undergone active surveillance, radiation therapy, or had a radical prostatectomy,” said Dr. Royce, a faculty member in radiation oncology at Wake Forest University School of Medicine in Winston-Salem, North Carolina. “The prognostic risk result reflects the patient’s prognosis regardless of the treatment path chosen.”

Dr. Royce said the new test predicts the risk for developing distant metastasis in 10 years. For the population considering active surveillance, it also can predict the likelihood their cancer will show more aggressive features. The test does not make a clinical recommendation, he added.

“Ultimately, that’s a very personal decision between the patient and their physician, and we view it as supporting that decision-making process,” he said.

The test is available in all states but New York and California, where the company is now, in discussions with regulators for approval, according to Dr. Royce. He said the company is in discussion with private insurers to set reimbursement and payment rates. In January 2024, Medicare set a payment rate of $700 for the AI test, which carries no out-of-pocket costs for patients. 

The first indication for the test was for localized prostate cancer, prognosticating the risk for distant metastases and death from prostate cancer. It can also predict if an individual will benefit from androgen deprivation therapy (ADT). Dr. Royce said up to 60% of patients with intermediate risk prostate cancer now can avoid ADT and its serious side effects, such as brain fog, weight gain, and reduction in muscle mass.

In March, the National Comprehensive Cancer Network, an alliance of 33 cancer centers included Artera as the first AI test in its Clinical Practice Guidelines in Oncology.

Dr. Royce said active surveillance is a new application of the test. The test was initially developed on a foundational study of almost 22,000 pathology slides from nearly 7000 patients published in npj Digital Medicine in 2022.

Todd Morgan, MD, chief of the Division of Urologic Oncology at the University of Michigan in Ann Arbor, and coauthor of the foundational study, said the AI test adds another layer of data to making clinical decisions for lower-risk patients.

“The technology is a big deal. The ability to use digital images to make accurate prognostic estimates is pretty remarkable, and this is the first test in any disease site to do this,” Dr. Morgan said. “Ultimately, this means tests may someday be performed by just sending images rather than sending actual tissue to an outside laboratory. Is the AI test dramatically more accurate than the genomic platforms? That’s TBD [to be determined].”

Dr. Royce said Artera is now working on a version of its test to inform men with higher-risk prostate cancer how long ADT should last and what the prognosis is for patients who have undergone prostatectomy based on their surgical specimen. The current test uses samples from the prostate biopsy, which are processed in a central lab. 

Dr. Royce said the company would like to eventually perform the test using digital images of pathology slides only.

Dr. Morgan reported no conflicts of interest.
 

A version of this article first appeared on Medscape.com.

In the first randomized controlled trial of prednisone for postvasectomy reversals, fertility researchers found that a high dose of the steroid reduced the rate of subsequent pregnancy.

“This is the first time it’s been shown that high doses [of prednisone] can make someone infertile,” said Landon Trost, MD, director of the Male Fertility and Peyronie’s Clinic in Orem, Utah, and a faculty member at Mayo Clinic, in Rochester, Minnesota, who presented the study (Abstract MP42-19) on May 4 at the 2024 annual meeting of the American Urological Association (AUA) in San Antonio, Texas. 

Dr. Trost called the findings “a real shock. I almost didn’t believe the data when I saw it. It opens up a whole new set of areas for research and exploration.”

Dr. Trost’s clinic performs 1200 reversals per year out of the estimated 20,000 performed annually in the United States, he said. He said his practice has stopped using high-dose prednisone as a result of the study, which he performed at his own expense to examine the varying protocols for vasectomy reversal.

William Berg, MD, director of the Stony Brook Urology Men’s Health Program, in Stony Brook, New York, said that the expected patency rate for modern postvasectomy reversals, if performed properly, can be as high as 98%. However, in some men, patency occurs initially, but the accumulation of scar tissue at the site of reversal causes sperm counts in ejaculate to drop to zero.

Since the 1970s, urologists — with limited research to back — the practice  prescribed prednisone to patients with the goal of preventing scarring and blockages associated with vasectomy reversals. Dr. Berg called this practice “unsubstantiated” and noted that Dr. Trost’s study is the first prospective randomized controlled trial of this approach.

The study enrolled 75 men, with a mean age of roughly 38 years. The mean time since vasectomy was 6.6 years.

The low-dose arm (25 patients) received 5 mg of prednisone per week alternating with no treatment per week over 6 months. The high-dose arm (n = 14) received 20 mg of prednisone, tapered to 10 mg, 5 mg, and then off over 1 month, followed by every other month for 6 months. A prednisone-as-needed group (n = 11) received a tapered course of prednisone on the basis of whether they had decreasing or zero sperm counts. They received 20 mg for 5 days, 10 mg for 5 days, and 5 mg for 20 days.

A control arm (n = 25) received no prednisone.

Urologists typically use patency rates to measure success of vasectomy reversals. The patency rates at 12 months in Dr. Trost’s study were 100% in the control participants, prednisone-as-needed, and low-dose groups and 92% (13/14) in the high-dose group. 

Dr. Trost said that the story was told in the pregnancy rates. At the 1-year mark, pregnancy rates were 67% in the low-risk group and 65% in the control group but 38% and 17% in the prednisone-as-needed and high-dose group, respectively (P = .02).

The mean maximum sperm concentration was 40 million per mL, ranging from 29.7 million per mL for men in the control group to 54.3 million per mL in the low-dose group.

Dr. Trost said that he immediately stopped using high doses of prednisone in his practice and predicted that other clinics would follow suit. 

Dr. Berg said the drop in pregnancies with higher doses of prednisone is a first-time finding and suggests that a high dose may “be detrimental to sperm function in some way. I don’t think this ever has been described before.”

Dr. Trost financed the study himself. Dr. Berg reported no conflicts.

A version of this article first appeared on Medscape.com.

In the first randomized controlled trial of prednisone for postvasectomy reversals, fertility researchers found that a high dose of the steroid reduced the rate of subsequent pregnancy.

“This is the first time it’s been shown that high doses [of prednisone] can make someone infertile,” said Landon Trost, MD, director of the Male Fertility and Peyronie’s Clinic in Orem, Utah, and a faculty member at Mayo Clinic, in Rochester, Minnesota, who presented the study (Abstract MP42-19) on May 4 at the 2024 annual meeting of the American Urological Association (AUA) in San Antonio, Texas. 

Dr. Trost called the findings “a real shock. I almost didn’t believe the data when I saw it. It opens up a whole new set of areas for research and exploration.”

Dr. Trost’s clinic performs 1200 reversals per year out of the estimated 20,000 performed annually in the United States, he said. He said his practice has stopped using high-dose prednisone as a result of the study, which he performed at his own expense to examine the varying protocols for vasectomy reversal.

William Berg, MD, director of the Stony Brook Urology Men’s Health Program, in Stony Brook, New York, said that the expected patency rate for modern postvasectomy reversals, if performed properly, can be as high as 98%. However, in some men, patency occurs initially, but the accumulation of scar tissue at the site of reversal causes sperm counts in ejaculate to drop to zero.

Since the 1970s, urologists — with limited research to back — the practice  prescribed prednisone to patients with the goal of preventing scarring and blockages associated with vasectomy reversals. Dr. Berg called this practice “unsubstantiated” and noted that Dr. Trost’s study is the first prospective randomized controlled trial of this approach.

The study enrolled 75 men, with a mean age of roughly 38 years. The mean time since vasectomy was 6.6 years.

The low-dose arm (25 patients) received 5 mg of prednisone per week alternating with no treatment per week over 6 months. The high-dose arm (n = 14) received 20 mg of prednisone, tapered to 10 mg, 5 mg, and then off over 1 month, followed by every other month for 6 months. A prednisone-as-needed group (n = 11) received a tapered course of prednisone on the basis of whether they had decreasing or zero sperm counts. They received 20 mg for 5 days, 10 mg for 5 days, and 5 mg for 20 days.

A control arm (n = 25) received no prednisone.

Urologists typically use patency rates to measure success of vasectomy reversals. The patency rates at 12 months in Dr. Trost’s study were 100% in the control participants, prednisone-as-needed, and low-dose groups and 92% (13/14) in the high-dose group. 

Dr. Trost said that the story was told in the pregnancy rates. At the 1-year mark, pregnancy rates were 67% in the low-risk group and 65% in the control group but 38% and 17% in the prednisone-as-needed and high-dose group, respectively (P = .02).

The mean maximum sperm concentration was 40 million per mL, ranging from 29.7 million per mL for men in the control group to 54.3 million per mL in the low-dose group.

Dr. Trost said that he immediately stopped using high doses of prednisone in his practice and predicted that other clinics would follow suit. 

Dr. Berg said the drop in pregnancies with higher doses of prednisone is a first-time finding and suggests that a high dose may “be detrimental to sperm function in some way. I don’t think this ever has been described before.”

Dr. Trost financed the study himself. Dr. Berg reported no conflicts.

A version of this article first appeared on Medscape.com.

In the first randomized controlled trial of prednisone for postvasectomy reversals, fertility researchers found that a high dose of the steroid reduced the rate of subsequent pregnancy.

“This is the first time it’s been shown that high doses [of prednisone] can make someone infertile,” said Landon Trost, MD, director of the Male Fertility and Peyronie’s Clinic in Orem, Utah, and a faculty member at Mayo Clinic, in Rochester, Minnesota, who presented the study (Abstract MP42-19) on May 4 at the 2024 annual meeting of the American Urological Association (AUA) in San Antonio, Texas. 

Dr. Trost called the findings “a real shock. I almost didn’t believe the data when I saw it. It opens up a whole new set of areas for research and exploration.”

Dr. Trost’s clinic performs 1200 reversals per year out of the estimated 20,000 performed annually in the United States, he said. He said his practice has stopped using high-dose prednisone as a result of the study, which he performed at his own expense to examine the varying protocols for vasectomy reversal.

William Berg, MD, director of the Stony Brook Urology Men’s Health Program, in Stony Brook, New York, said that the expected patency rate for modern postvasectomy reversals, if performed properly, can be as high as 98%. However, in some men, patency occurs initially, but the accumulation of scar tissue at the site of reversal causes sperm counts in ejaculate to drop to zero.

Since the 1970s, urologists — with limited research to back — the practice  prescribed prednisone to patients with the goal of preventing scarring and blockages associated with vasectomy reversals. Dr. Berg called this practice “unsubstantiated” and noted that Dr. Trost’s study is the first prospective randomized controlled trial of this approach.

The study enrolled 75 men, with a mean age of roughly 38 years. The mean time since vasectomy was 6.6 years.

The low-dose arm (25 patients) received 5 mg of prednisone per week alternating with no treatment per week over 6 months. The high-dose arm (n = 14) received 20 mg of prednisone, tapered to 10 mg, 5 mg, and then off over 1 month, followed by every other month for 6 months. A prednisone-as-needed group (n = 11) received a tapered course of prednisone on the basis of whether they had decreasing or zero sperm counts. They received 20 mg for 5 days, 10 mg for 5 days, and 5 mg for 20 days.

A control arm (n = 25) received no prednisone.

Urologists typically use patency rates to measure success of vasectomy reversals. The patency rates at 12 months in Dr. Trost’s study were 100% in the control participants, prednisone-as-needed, and low-dose groups and 92% (13/14) in the high-dose group. 

Dr. Trost said that the story was told in the pregnancy rates. At the 1-year mark, pregnancy rates were 67% in the low-risk group and 65% in the control group but 38% and 17% in the prednisone-as-needed and high-dose group, respectively (P = .02).

The mean maximum sperm concentration was 40 million per mL, ranging from 29.7 million per mL for men in the control group to 54.3 million per mL in the low-dose group.

Dr. Trost said that he immediately stopped using high doses of prednisone in his practice and predicted that other clinics would follow suit. 

Dr. Berg said the drop in pregnancies with higher doses of prednisone is a first-time finding and suggests that a high dose may “be detrimental to sperm function in some way. I don’t think this ever has been described before.”

Dr. Trost financed the study himself. Dr. Berg reported no conflicts.

A version of this article first appeared on Medscape.com.

An experimental handheld ultrasonic device used in an office setting was shown to guide residual kidney stone fragments out of the body and markedly reduce the risk for relapse, researchers reported (Abstract MP29-10) at the 2024 annual meeting of the American Urological Association AUA in San Antonio, Texas.

Mathew Sorensen, MD, MS, an associate professor of urology at the University of Washington, Seattle, and director of the Comprehensive Metabolic Stone Clinic at the Puget Sound VA, said that the risk for relapse of kidney stones was 70% lower in the treatment group than in the control group.

“This is an ultrasound-based propulsion procedure that is not like anything else that has ever existed. There’s nothing else that’s like it,” Dr. Sorensen said. “Essentially, in a session in the office with no anesthesia, we can use ultrasound energy to focus on those fragments and try to push them out of the unfavorable areas of the kidney.”

Roughly 20%-30% of patients who undergo surgery to remove kidney stones have residual fragments that can ultimately cause pain and send them to the emergency department or into hospital admission for treatment.

In the new study, 82 patients with stone fragments ≤ 5 mm were randomly assigned to receive the ultrasound treatment — which Dr. Sorensen and his colleagues developed over the past decade — or no procedure.

During a median follow-up of 2.6 years, 20% of patients in the treatment group experienced relapse of stones compared with 50% of patients in the control group. 

Relapse was measured as the future occurrence of urgent medical visits for stone-related symptoms, surgeries, or growth of the residual fragments as measured on annual CT.

Dr. Sorensen and his colleagues found asymptomatic passage of fragments was twelvefold higher in the treatment group in the first 3 weeks (60% vs 5%). Asymptomatic passage was similar in both groups after 3 weeks.

Dr. Sorensen said that mild discomfort after the procedure was common, occurring in 38% of patients who underwent the treatment, but that it was short-lived and resolved without intervention; 8% of the treatment group and 7% of the control group had blood in the urine.

The propulsion device is available at two test sites in the University of Washington system; the manufacturer, SonoMotion Inc, a spinoff from the institution, is seeking US Food and Drug Administration approval for the technology, Dr. Sorensen said. 

David Schulsinger, MD, an associate professor in the Department of Urology at Stony Brook University Hospital, Stony Brook, New York, said that patients with stone fragments currently have two options: follow-up surgery or active surveillance.

“With this new device, we actually have the potential for doing one other thing, and that is treating these patients noninvasively and without anesthesia,” Dr. Schulsinger said. “Once it’s ready for prime time, I think [ultrasonic propulsion] will be very well accepted among urologists to manage patients with asymptomatic residual stones.”

Dr. Sorensen is an advisor and equity holder in SonoMotion Inc. Dr. Schulsinger reported no relevant financial conflicts of interest.

A version of this article first appeared on Medscape.com.

An experimental handheld ultrasonic device used in an office setting was shown to guide residual kidney stone fragments out of the body and markedly reduce the risk for relapse, researchers reported (Abstract MP29-10) at the 2024 annual meeting of the American Urological Association AUA in San Antonio, Texas.

Mathew Sorensen, MD, MS, an associate professor of urology at the University of Washington, Seattle, and director of the Comprehensive Metabolic Stone Clinic at the Puget Sound VA, said that the risk for relapse of kidney stones was 70% lower in the treatment group than in the control group.

“This is an ultrasound-based propulsion procedure that is not like anything else that has ever existed. There’s nothing else that’s like it,” Dr. Sorensen said. “Essentially, in a session in the office with no anesthesia, we can use ultrasound energy to focus on those fragments and try to push them out of the unfavorable areas of the kidney.”

Roughly 20%-30% of patients who undergo surgery to remove kidney stones have residual fragments that can ultimately cause pain and send them to the emergency department or into hospital admission for treatment.

In the new study, 82 patients with stone fragments ≤ 5 mm were randomly assigned to receive the ultrasound treatment — which Dr. Sorensen and his colleagues developed over the past decade — or no procedure.

During a median follow-up of 2.6 years, 20% of patients in the treatment group experienced relapse of stones compared with 50% of patients in the control group. 

Relapse was measured as the future occurrence of urgent medical visits for stone-related symptoms, surgeries, or growth of the residual fragments as measured on annual CT.

Dr. Sorensen and his colleagues found asymptomatic passage of fragments was twelvefold higher in the treatment group in the first 3 weeks (60% vs 5%). Asymptomatic passage was similar in both groups after 3 weeks.

Dr. Sorensen said that mild discomfort after the procedure was common, occurring in 38% of patients who underwent the treatment, but that it was short-lived and resolved without intervention; 8% of the treatment group and 7% of the control group had blood in the urine.

The propulsion device is available at two test sites in the University of Washington system; the manufacturer, SonoMotion Inc, a spinoff from the institution, is seeking US Food and Drug Administration approval for the technology, Dr. Sorensen said. 

David Schulsinger, MD, an associate professor in the Department of Urology at Stony Brook University Hospital, Stony Brook, New York, said that patients with stone fragments currently have two options: follow-up surgery or active surveillance.

“With this new device, we actually have the potential for doing one other thing, and that is treating these patients noninvasively and without anesthesia,” Dr. Schulsinger said. “Once it’s ready for prime time, I think [ultrasonic propulsion] will be very well accepted among urologists to manage patients with asymptomatic residual stones.”

Dr. Sorensen is an advisor and equity holder in SonoMotion Inc. Dr. Schulsinger reported no relevant financial conflicts of interest.

A version of this article first appeared on Medscape.com.

An experimental handheld ultrasonic device used in an office setting was shown to guide residual kidney stone fragments out of the body and markedly reduce the risk for relapse, researchers reported (Abstract MP29-10) at the 2024 annual meeting of the American Urological Association AUA in San Antonio, Texas.

Mathew Sorensen, MD, MS, an associate professor of urology at the University of Washington, Seattle, and director of the Comprehensive Metabolic Stone Clinic at the Puget Sound VA, said that the risk for relapse of kidney stones was 70% lower in the treatment group than in the control group.

“This is an ultrasound-based propulsion procedure that is not like anything else that has ever existed. There’s nothing else that’s like it,” Dr. Sorensen said. “Essentially, in a session in the office with no anesthesia, we can use ultrasound energy to focus on those fragments and try to push them out of the unfavorable areas of the kidney.”

Roughly 20%-30% of patients who undergo surgery to remove kidney stones have residual fragments that can ultimately cause pain and send them to the emergency department or into hospital admission for treatment.

In the new study, 82 patients with stone fragments ≤ 5 mm were randomly assigned to receive the ultrasound treatment — which Dr. Sorensen and his colleagues developed over the past decade — or no procedure.

During a median follow-up of 2.6 years, 20% of patients in the treatment group experienced relapse of stones compared with 50% of patients in the control group. 

Relapse was measured as the future occurrence of urgent medical visits for stone-related symptoms, surgeries, or growth of the residual fragments as measured on annual CT.

Dr. Sorensen and his colleagues found asymptomatic passage of fragments was twelvefold higher in the treatment group in the first 3 weeks (60% vs 5%). Asymptomatic passage was similar in both groups after 3 weeks.

Dr. Sorensen said that mild discomfort after the procedure was common, occurring in 38% of patients who underwent the treatment, but that it was short-lived and resolved without intervention; 8% of the treatment group and 7% of the control group had blood in the urine.

The propulsion device is available at two test sites in the University of Washington system; the manufacturer, SonoMotion Inc, a spinoff from the institution, is seeking US Food and Drug Administration approval for the technology, Dr. Sorensen said. 

David Schulsinger, MD, an associate professor in the Department of Urology at Stony Brook University Hospital, Stony Brook, New York, said that patients with stone fragments currently have two options: follow-up surgery or active surveillance.

“With this new device, we actually have the potential for doing one other thing, and that is treating these patients noninvasively and without anesthesia,” Dr. Schulsinger said. “Once it’s ready for prime time, I think [ultrasonic propulsion] will be very well accepted among urologists to manage patients with asymptomatic residual stones.”

Dr. Sorensen is an advisor and equity holder in SonoMotion Inc. Dr. Schulsinger reported no relevant financial conflicts of interest.

A version of this article first appeared on Medscape.com.

Up to 60% of men with erectile dysfunction who were not candidates for phosphodiesterase 5 (PDE5) inhibitors achieved erections in less than 10 minutes after a single application of a first-on-the-market nonprescription gel to the glans, a new study found. 

Wayne Hellstrom, MD, chief of andrology at Tulane School of Medicine in New Orleans, who presented the study of MED3000 [Eroxon] on May 5 at the 2024 annual meeting of the American Urological Association in San Antonio, Texas, said that the gel is considered to be a device by the US Food and Drug Administration (FDA). The agency approved the product in June 2023.

A spokesman for Futura, which makes MED3000, said that the gel will be on the market 2025. No price for the United States has been announced, but a four-pack of single-use tubes sells for the equivalent of roughly $31 in the United Kingdom.

Dr. Hellstrom, a former adviser to Futura, he said he expects MED3000 will be “a potential first-line therapy in addition to PDE5 inhibitors,” which are vasodilating drugs that stimulate the corpora cavernosa of the penis, facilitating erection with sexual stimulation.

He noted that PDE5s are contraindicated for many men; are not tolerated in others; are not completely effective; or work too slowly, taking 1-2 hours to work. As a result, up to 50% of patients cease using a PDE5 inhibitor within 1 year, he said. 

Futura said the gel contains a combination of volatile solvents which, when applied to the head of the penis, evaporate rapidly, stimulating nerve endings through an initial cooling effect followed by a warming sensation. This reaction releases nitric oxide, relaxing the smooth muscle tissue inside the penis and increasing blood flow that is needed to obtain an erection.

Dr. Hellstrom noted that MED3000 is noninvasive and causes no side effects and is slightly more effective if applied by a partner.

The new findings come from two studies of 250 men with erectile dysfunction (FM57) who used MED3000 over 12 weeks and a randomly assigned arm (FM71) with two groups of 48 men who used either MED3000 or 5 mg of tadalafil over 24 weeks.

Erections were achieved in less than 10 minutes in 60.1% of men in the FM57 group and 44.9% of those in the FM71 group.

Overall, less than 2% of the men who usedMED3000 and 4% of those who took tadalafil reported adverse effects. These events included headaches in 3% of the combined MED3000 group and 19.1% of the tadalafil group. Roughly 1% of men who used MED3000 reported penile burning sensation compared with none in the group taking tadalafil.
 

Problematic Design? 

Kevin McVary, MD, a professor of urology at Stritch School of Medicine of Loyola University, outside of Chicago, and director of the Center for Male Health, criticized the study design and added that he did not believe MED3000 had been proven beneficial.

“Are they expecting the Cialis 5 mg to work within 10 minutes? Because it doesn’t,” Dr. McVary said. “It doesn’t get absorbed into the bloodstream for about 2.5 hours.”

Dr. McVary said that men with erectile dysfunction will probably do anything to avoid seeing a physician about the condition, which could make MED3000 highly marketable.

However, he said, examinations would be important to detect unrecognized underlying cardiac disease, especially in younger men. “ED can function as the classic canary in a coal mine where it tells you who’s at risk for unexpected early death,” he said.

Dr. Hellstrom is a former adviser to Futura Medical Developments, which funded the research. Dr. McVary reported no relevant financial conflicts of interest.  
 

A version of this article appeared on Medscape.com .

Up to 60% of men with erectile dysfunction who were not candidates for phosphodiesterase 5 (PDE5) inhibitors achieved erections in less than 10 minutes after a single application of a first-on-the-market nonprescription gel to the glans, a new study found. 

Wayne Hellstrom, MD, chief of andrology at Tulane School of Medicine in New Orleans, who presented the study of MED3000 [Eroxon] on May 5 at the 2024 annual meeting of the American Urological Association in San Antonio, Texas, said that the gel is considered to be a device by the US Food and Drug Administration (FDA). The agency approved the product in June 2023.

A spokesman for Futura, which makes MED3000, said that the gel will be on the market 2025. No price for the United States has been announced, but a four-pack of single-use tubes sells for the equivalent of roughly $31 in the United Kingdom.

Dr. Hellstrom, a former adviser to Futura, he said he expects MED3000 will be “a potential first-line therapy in addition to PDE5 inhibitors,” which are vasodilating drugs that stimulate the corpora cavernosa of the penis, facilitating erection with sexual stimulation.

He noted that PDE5s are contraindicated for many men; are not tolerated in others; are not completely effective; or work too slowly, taking 1-2 hours to work. As a result, up to 50% of patients cease using a PDE5 inhibitor within 1 year, he said. 

Futura said the gel contains a combination of volatile solvents which, when applied to the head of the penis, evaporate rapidly, stimulating nerve endings through an initial cooling effect followed by a warming sensation. This reaction releases nitric oxide, relaxing the smooth muscle tissue inside the penis and increasing blood flow that is needed to obtain an erection.

Dr. Hellstrom noted that MED3000 is noninvasive and causes no side effects and is slightly more effective if applied by a partner.

The new findings come from two studies of 250 men with erectile dysfunction (FM57) who used MED3000 over 12 weeks and a randomly assigned arm (FM71) with two groups of 48 men who used either MED3000 or 5 mg of tadalafil over 24 weeks.

Erections were achieved in less than 10 minutes in 60.1% of men in the FM57 group and 44.9% of those in the FM71 group.

Overall, less than 2% of the men who usedMED3000 and 4% of those who took tadalafil reported adverse effects. These events included headaches in 3% of the combined MED3000 group and 19.1% of the tadalafil group. Roughly 1% of men who used MED3000 reported penile burning sensation compared with none in the group taking tadalafil.
 

Problematic Design? 

Kevin McVary, MD, a professor of urology at Stritch School of Medicine of Loyola University, outside of Chicago, and director of the Center for Male Health, criticized the study design and added that he did not believe MED3000 had been proven beneficial.

“Are they expecting the Cialis 5 mg to work within 10 minutes? Because it doesn’t,” Dr. McVary said. “It doesn’t get absorbed into the bloodstream for about 2.5 hours.”

Dr. McVary said that men with erectile dysfunction will probably do anything to avoid seeing a physician about the condition, which could make MED3000 highly marketable.

However, he said, examinations would be important to detect unrecognized underlying cardiac disease, especially in younger men. “ED can function as the classic canary in a coal mine where it tells you who’s at risk for unexpected early death,” he said.

Dr. Hellstrom is a former adviser to Futura Medical Developments, which funded the research. Dr. McVary reported no relevant financial conflicts of interest.  
 

A version of this article appeared on Medscape.com .

Up to 60% of men with erectile dysfunction who were not candidates for phosphodiesterase 5 (PDE5) inhibitors achieved erections in less than 10 minutes after a single application of a first-on-the-market nonprescription gel to the glans, a new study found. 

Wayne Hellstrom, MD, chief of andrology at Tulane School of Medicine in New Orleans, who presented the study of MED3000 [Eroxon] on May 5 at the 2024 annual meeting of the American Urological Association in San Antonio, Texas, said that the gel is considered to be a device by the US Food and Drug Administration (FDA). The agency approved the product in June 2023.

A spokesman for Futura, which makes MED3000, said that the gel will be on the market 2025. No price for the United States has been announced, but a four-pack of single-use tubes sells for the equivalent of roughly $31 in the United Kingdom.

Dr. Hellstrom, a former adviser to Futura, he said he expects MED3000 will be “a potential first-line therapy in addition to PDE5 inhibitors,” which are vasodilating drugs that stimulate the corpora cavernosa of the penis, facilitating erection with sexual stimulation.

He noted that PDE5s are contraindicated for many men; are not tolerated in others; are not completely effective; or work too slowly, taking 1-2 hours to work. As a result, up to 50% of patients cease using a PDE5 inhibitor within 1 year, he said. 

Futura said the gel contains a combination of volatile solvents which, when applied to the head of the penis, evaporate rapidly, stimulating nerve endings through an initial cooling effect followed by a warming sensation. This reaction releases nitric oxide, relaxing the smooth muscle tissue inside the penis and increasing blood flow that is needed to obtain an erection.

Dr. Hellstrom noted that MED3000 is noninvasive and causes no side effects and is slightly more effective if applied by a partner.

The new findings come from two studies of 250 men with erectile dysfunction (FM57) who used MED3000 over 12 weeks and a randomly assigned arm (FM71) with two groups of 48 men who used either MED3000 or 5 mg of tadalafil over 24 weeks.

Erections were achieved in less than 10 minutes in 60.1% of men in the FM57 group and 44.9% of those in the FM71 group.

Overall, less than 2% of the men who usedMED3000 and 4% of those who took tadalafil reported adverse effects. These events included headaches in 3% of the combined MED3000 group and 19.1% of the tadalafil group. Roughly 1% of men who used MED3000 reported penile burning sensation compared with none in the group taking tadalafil.
 

Problematic Design? 

Kevin McVary, MD, a professor of urology at Stritch School of Medicine of Loyola University, outside of Chicago, and director of the Center for Male Health, criticized the study design and added that he did not believe MED3000 had been proven beneficial.

“Are they expecting the Cialis 5 mg to work within 10 minutes? Because it doesn’t,” Dr. McVary said. “It doesn’t get absorbed into the bloodstream for about 2.5 hours.”

Dr. McVary said that men with erectile dysfunction will probably do anything to avoid seeing a physician about the condition, which could make MED3000 highly marketable.

However, he said, examinations would be important to detect unrecognized underlying cardiac disease, especially in younger men. “ED can function as the classic canary in a coal mine where it tells you who’s at risk for unexpected early death,” he said.

Dr. Hellstrom is a former adviser to Futura Medical Developments, which funded the research. Dr. McVary reported no relevant financial conflicts of interest.  
 

A version of this article appeared on Medscape.com .

An “inevitable” global surge in prostate cancer is coming, with a worldwide doubling of cases to 2.9 million and an 85% increase in deaths to nearly 700,000 by the year 2040, the Lancet Commission on Prostate Cancer warned this week.

At a meeting of urologists in Paris, the commission said that the acceleration is already underway in high-income countries such as the United States and the United Kingdom but will gain momentum in low- and medium-income countries.

Nick James, MD, lead author of The Lancet report and professor of prostate and bladder cancer research at The Institute of Cancer Research in London, said that the surge, in part, is a medical success story.

“Prostate cancer paradoxically is a problem baked into the biology. Men get prostate cancer as they age,” Dr. James told this news organization. 

“There is a big rise in the high-income countries. But we’re going to see a big rise in the number of 50-, 60-, 70-year-olds in the coming decades in the poorer countries, and with that comes more prostate cancer. High-income countries such as the UK and USA will also see smaller increases for the same reason.”

According to the report, to be presented April 6 at the 2024 European Association of Urology Congress in Paris, “The case for prostate cancer screening for all men aged 50-70 years (and all men of African origin aged 45–70 years) in high-income countries is strengthening with improved use of technologies such as MRI and growing evidence for the safety of active surveillance.”

Andrew Vickers, PhD, a biostatistician at Memorial Sloan Kettering Cancer Center in New York City, said that the Lancet Commission came to similar conclusions as he and an international group of researchers did in a 2023 policy paper in The BMJ. A major gap, Dr. Vickers said, is misuse of prostate-specific antigen (PSA) screening. 

“We found that the ubiquitous policy compromise of letting patients decide for themselves about PSA has led to the worst possible outcomes of overuse in men unlikely to benefit, high rates of overdiagnosis and overtreatment, and economic and racial inequity,” Dr. Vickers said. “Our view is that PSA screening should be done well — by implementing straightforward harm-reduction strategies like restricting screening in older men and use of secondary tests before biopsy — or not at all.”

Dr. James said that undertreatment of advanced disease is widespread; only about 30%-40% of men in the United States receive combination hormone therapy for metastatic disease, for example. “Simply doing what we know works would improve outcomes,” he said.

Dr. James said that men of African ancestry are twice as likely to develop prostate cancer, but whether treatment should follow a different approach in these men is unclear. The new report stressed the need to include more men of African ancestry in research.

Brandon Mahal, MD, vice chair of research in radiation oncology the University of Miami Sylvester Comprehensive Cancer Center and a coauthor of the report, said that new approaches are needed to enable earlier diagnosis of prostate cancer in men in low- to middle-income countries, where most patients present with metastatic disease and are less likely to survive for long periods.

Dr. James recommended pop-up clinics and mobile testing to encourage men who are at high risk for prostate cancer but feel well to detect lethal cancers early.

In England, for example, Dr. James helped introduce an outreach program called The Man Van which provided free health checks, including PSA tests, to high-risk men in London. 

“By bringing a van with quick and easy testing straight to men at work and in the community, and targeting those who have a higher risk of prostate cancer, we provided thousands of health checks which resulted in almost 100 cancer diagnoses in men who might otherwise have only seen a doctor once their cancer has progressed to a more advanced stage,” he said.

He noted that the medical community worldwide is ill-prepared for the onslaught of prostate cancer cases.

“The solution cannot be training more urologists, radiation oncologists, pathologists, and radiologists because it simply takes too long,” Dr. James said. However, increased use of nurses and artificial intelligence may help. “In my own hospital, biopsies are a nurse-led and -delivered service. AI is extraordinarily good at diagnosis already and will only get better,” he said.

In poorer countries, smartphones could fill gaps too. “The same technology that does face recognition already can say that’s a Gleason 7 prostate cancer,” Dr. James said. “It’s not being rolled out in countries like America of course because pathologists’ income is at risk.”

Dr. James, Dr. Vickers, and Dr. Mahal reported no relevant financial conflicts of interest. 
 

A version of this article appeared on Medscape.com.

An “inevitable” global surge in prostate cancer is coming, with a worldwide doubling of cases to 2.9 million and an 85% increase in deaths to nearly 700,000 by the year 2040, the Lancet Commission on Prostate Cancer warned this week.

At a meeting of urologists in Paris, the commission said that the acceleration is already underway in high-income countries such as the United States and the United Kingdom but will gain momentum in low- and medium-income countries.

Nick James, MD, lead author of The Lancet report and professor of prostate and bladder cancer research at The Institute of Cancer Research in London, said that the surge, in part, is a medical success story.

“Prostate cancer paradoxically is a problem baked into the biology. Men get prostate cancer as they age,” Dr. James told this news organization. 

“There is a big rise in the high-income countries. But we’re going to see a big rise in the number of 50-, 60-, 70-year-olds in the coming decades in the poorer countries, and with that comes more prostate cancer. High-income countries such as the UK and USA will also see smaller increases for the same reason.”

According to the report, to be presented April 6 at the 2024 European Association of Urology Congress in Paris, “The case for prostate cancer screening for all men aged 50-70 years (and all men of African origin aged 45–70 years) in high-income countries is strengthening with improved use of technologies such as MRI and growing evidence for the safety of active surveillance.”

Andrew Vickers, PhD, a biostatistician at Memorial Sloan Kettering Cancer Center in New York City, said that the Lancet Commission came to similar conclusions as he and an international group of researchers did in a 2023 policy paper in The BMJ. A major gap, Dr. Vickers said, is misuse of prostate-specific antigen (PSA) screening. 

“We found that the ubiquitous policy compromise of letting patients decide for themselves about PSA has led to the worst possible outcomes of overuse in men unlikely to benefit, high rates of overdiagnosis and overtreatment, and economic and racial inequity,” Dr. Vickers said. “Our view is that PSA screening should be done well — by implementing straightforward harm-reduction strategies like restricting screening in older men and use of secondary tests before biopsy — or not at all.”

Dr. James said that undertreatment of advanced disease is widespread; only about 30%-40% of men in the United States receive combination hormone therapy for metastatic disease, for example. “Simply doing what we know works would improve outcomes,” he said.

Dr. James said that men of African ancestry are twice as likely to develop prostate cancer, but whether treatment should follow a different approach in these men is unclear. The new report stressed the need to include more men of African ancestry in research.

Brandon Mahal, MD, vice chair of research in radiation oncology the University of Miami Sylvester Comprehensive Cancer Center and a coauthor of the report, said that new approaches are needed to enable earlier diagnosis of prostate cancer in men in low- to middle-income countries, where most patients present with metastatic disease and are less likely to survive for long periods.

Dr. James recommended pop-up clinics and mobile testing to encourage men who are at high risk for prostate cancer but feel well to detect lethal cancers early.

In England, for example, Dr. James helped introduce an outreach program called The Man Van which provided free health checks, including PSA tests, to high-risk men in London. 

“By bringing a van with quick and easy testing straight to men at work and in the community, and targeting those who have a higher risk of prostate cancer, we provided thousands of health checks which resulted in almost 100 cancer diagnoses in men who might otherwise have only seen a doctor once their cancer has progressed to a more advanced stage,” he said.

He noted that the medical community worldwide is ill-prepared for the onslaught of prostate cancer cases.

“The solution cannot be training more urologists, radiation oncologists, pathologists, and radiologists because it simply takes too long,” Dr. James said. However, increased use of nurses and artificial intelligence may help. “In my own hospital, biopsies are a nurse-led and -delivered service. AI is extraordinarily good at diagnosis already and will only get better,” he said.

In poorer countries, smartphones could fill gaps too. “The same technology that does face recognition already can say that’s a Gleason 7 prostate cancer,” Dr. James said. “It’s not being rolled out in countries like America of course because pathologists’ income is at risk.”

Dr. James, Dr. Vickers, and Dr. Mahal reported no relevant financial conflicts of interest. 
 

A version of this article appeared on Medscape.com.

An “inevitable” global surge in prostate cancer is coming, with a worldwide doubling of cases to 2.9 million and an 85% increase in deaths to nearly 700,000 by the year 2040, the Lancet Commission on Prostate Cancer warned this week.

At a meeting of urologists in Paris, the commission said that the acceleration is already underway in high-income countries such as the United States and the United Kingdom but will gain momentum in low- and medium-income countries.

Nick James, MD, lead author of The Lancet report and professor of prostate and bladder cancer research at The Institute of Cancer Research in London, said that the surge, in part, is a medical success story.

“Prostate cancer paradoxically is a problem baked into the biology. Men get prostate cancer as they age,” Dr. James told this news organization. 

“There is a big rise in the high-income countries. But we’re going to see a big rise in the number of 50-, 60-, 70-year-olds in the coming decades in the poorer countries, and with that comes more prostate cancer. High-income countries such as the UK and USA will also see smaller increases for the same reason.”

According to the report, to be presented April 6 at the 2024 European Association of Urology Congress in Paris, “The case for prostate cancer screening for all men aged 50-70 years (and all men of African origin aged 45–70 years) in high-income countries is strengthening with improved use of technologies such as MRI and growing evidence for the safety of active surveillance.”

Andrew Vickers, PhD, a biostatistician at Memorial Sloan Kettering Cancer Center in New York City, said that the Lancet Commission came to similar conclusions as he and an international group of researchers did in a 2023 policy paper in The BMJ. A major gap, Dr. Vickers said, is misuse of prostate-specific antigen (PSA) screening. 

“We found that the ubiquitous policy compromise of letting patients decide for themselves about PSA has led to the worst possible outcomes of overuse in men unlikely to benefit, high rates of overdiagnosis and overtreatment, and economic and racial inequity,” Dr. Vickers said. “Our view is that PSA screening should be done well — by implementing straightforward harm-reduction strategies like restricting screening in older men and use of secondary tests before biopsy — or not at all.”

Dr. James said that undertreatment of advanced disease is widespread; only about 30%-40% of men in the United States receive combination hormone therapy for metastatic disease, for example. “Simply doing what we know works would improve outcomes,” he said.

Dr. James said that men of African ancestry are twice as likely to develop prostate cancer, but whether treatment should follow a different approach in these men is unclear. The new report stressed the need to include more men of African ancestry in research.

Brandon Mahal, MD, vice chair of research in radiation oncology the University of Miami Sylvester Comprehensive Cancer Center and a coauthor of the report, said that new approaches are needed to enable earlier diagnosis of prostate cancer in men in low- to middle-income countries, where most patients present with metastatic disease and are less likely to survive for long periods.

Dr. James recommended pop-up clinics and mobile testing to encourage men who are at high risk for prostate cancer but feel well to detect lethal cancers early.

In England, for example, Dr. James helped introduce an outreach program called The Man Van which provided free health checks, including PSA tests, to high-risk men in London. 

“By bringing a van with quick and easy testing straight to men at work and in the community, and targeting those who have a higher risk of prostate cancer, we provided thousands of health checks which resulted in almost 100 cancer diagnoses in men who might otherwise have only seen a doctor once their cancer has progressed to a more advanced stage,” he said.

He noted that the medical community worldwide is ill-prepared for the onslaught of prostate cancer cases.

“The solution cannot be training more urologists, radiation oncologists, pathologists, and radiologists because it simply takes too long,” Dr. James said. However, increased use of nurses and artificial intelligence may help. “In my own hospital, biopsies are a nurse-led and -delivered service. AI is extraordinarily good at diagnosis already and will only get better,” he said.

In poorer countries, smartphones could fill gaps too. “The same technology that does face recognition already can say that’s a Gleason 7 prostate cancer,” Dr. James said. “It’s not being rolled out in countries like America of course because pathologists’ income is at risk.”

Dr. James, Dr. Vickers, and Dr. Mahal reported no relevant financial conflicts of interest. 
 

A version of this article appeared on Medscape.com.

In 2013, a prostate-specific antigen (PSA) blood test revealed that Richard LaFrate’s levels had jumped. 

Previously in a normal range, his PSA was now above 6 ng/mL, indicating an elevated likelihood for prostate cancer. The jazz guitarist from Leesburg, Florida, then 70 years old, underwent a biopsy, which found two Gleason 6 lesions. 

Mr. LaFrate had low-risk prostate cancer.

Guidelines now recommend active surveillance for patients like Mr. LaFrate, who have low-risk disease. This strategy would mean monitoring the cancer until LaFrate required treatment, with the upside being he might never need therapy.

Mr. LaFrate’s urologist, however, was pushing whole gland surgery — an invasive and unnecessary procedure given his diagnosis and age. 

Mr. LaFrate decided to look for another doctor. He filled out a form online that pointed him to a new urologist who offered him one option: An investigational procedure known as high-intensity focused ultrasound.

At the time, high-intensity focused ultrasound — a form of focal therapy — was being studied in the United States to treat men with low or intermediate-risk prostate cancer, but it was still relatively early days.

Mr. LaFrate’s urologist asked him to pay $25,000 out of pocket to undergo the focal procedure at a clinic in the Bahamas. He refused and, ultimately, landed on active surveillance as the best strategy to manage for his low-risk disease.

That urologist was “a shyster in my opinion,” Mr. LaFrate said. 

Over the past 10 years, the popularity of focal therapy has grown among men with intermediate-risk prostate cancer — Gleason 3+4 (grade group 2) tumors — as an alternative to invasive surgery and active surveillance. Prestigious medical centers, such as Cleveland Clinic, Mayo Clinic, Memorial Sloan Kettering, UCLA, and the University of Chicago, routinely offer focal therapy. 

But use of the techniques remains controversial and costly.

As the Cleveland Clinic’s website acknowledges, although “the use of focal therapy for localized prostate cancer appears to be a promising development in a number of ways, it is still considered investigational and not yet part of standard therapy.” Major caveats to focal therapy include unknown long-term effectiveness, the possibility of leaving behind untreated cancer, and higher overall costs. 

No major national guidelines endorse the use of focal therapy, unless offered in a research or clinical trial setting. Insurance companies, such as Aetna, Blue Cross Blue Shield, and United, also consider focal therapy for prostate cancer investigational and don’t cover it.

Without a stamp of approval from guideline bodies and insurance companies, patients, like Mr. LaFrate, remain vulnerable to the high out-of-pocket costs for these focal techniques. 

“Almost every place charges $15,000-$30,000 in cash,” said Daniel Spratt, MD, radiation oncology chair at University Hospitals Seidman Cancer Center and Case Western Reserve University in Cleveland. 

Dr. Spratt has seen hundreds of patients after focal therapy, some from prominent centers, who have emptied their bank accounts to undergo treatment with the promise of great results and ultimately felt misled when the cancer has recurred.

“It pains me that there are doctors willing to ignore the Hippocratic oath of ‘Do No Harm’ simply to jump on this fad to bring in revenue,” Dr. Spratt said. 
 

Evidence-Based or Oversold?

Focal therapy gained a foothold in the United Kingdom well before the United States.

Hashim Ahmed, FRCS, urology chair at Imperial College London, has used focal therapy for 15 years, treated over 1000 patients, and taught dozens of surgeons how to use the leading focal therapies — focal cryoablation, in which surgeons use a needle-thin probe to target, freeze, and kill prostate tumors, as well as high-intensity focused ultrasound, which uses sound wave energy to superheat and kill tumors.

“Certainly, in the United Kingdom, focal therapy has been prime time in a number of centers for a number of years,” Dr. Ahmed said. 

In the United States, focal therapy has become an attractive option for men with prostate cancer who want to avoid radiation or radical prostatectomy but don’t feel comfortable simply monitoring their disease with active surveillance. Experts from specialized focal therapy centers touting the promise of this “innovative technique” predict its routine use in the next few years.

But the excitement surrounding the use of focal therapy in prostate cancer has outpaced broader acceptance.

In 2015, the FDA approved high-intensity focused ultrasound to treat prostatic disease, but not prostate cancer specifically. Although the approval language “means that companies cannot advertise that their devices can be used for prostate cancer,” physicians can still determine how to use the technology, which includes treating prostate cancer, Dr. Ahmed said. 

The evidence is starting to catch up to the demand. The latest research suggests that the partial-gland techniques may stand up well to radical prostatectomy.

A 2022 prospective database study comparing radical prostatectomies to focal therapy — mostly high-intensity focused ultrasound — in more than 800 men found similar rates of failure-free survival in the two groups at the 8-year follow-up. A 2019 registry study found that failure-free survival at 3 years was just over 90% in high and intermediate-risk patients receiving focal cryotherapy, with the rate rising to about 93% for the intermediate-risk group. And a 2018 prospective study of 625 patients with intermediate or high-risk prostate cancer who underwent high-intensity focused ultrasound had 5-year metastasis-free survival of 98% and overall survival rates of 100%.

One of the biggest draws of focal therapy vs more aggressive treatments is the “massive differences in side-effect profiles,” said Dr. Ahmed.

In a 2021 meta-analysis, researchers found that 6 months after high-intensity focused ultrasound, 98% of patients remained continent and 80% retained erectile function, while erectile dysfunction can occur in 30% to as many as 85% of patients following prostatectomy or radiotherapy and urinary incontinence can occur in as many as 40% of patients.

Despite these potential advantages of focal therapy, the long-term efficacy of the techniques remains uncertain.

A recent study from a team at MSK, for instance, reported that 40% of men with intermediate (grade 2) or high-risk (grade 3) disease had residual cancer following MRI-guided focused ultrasound. A 2020 prospective registry study found that almost 20% of patients undergoing high-intensity focal ultrasound required a second round following a recurrence. 

Dr. Spratt worries that patients who recur after focal therapy may go on to receive a second round — often offered at half price — and will still ultimately need surgery or radiation therapy later. By that point, however, patients may have spent as much as $45,000 — ie, $30,000 on the initial and another $15,000 on the follow-up procedure.

When patients see Dr. Spratt after a recurrence, he informs them that their side effects will be worse if he gives them radiation or surgery now vs if he had given them curative therapy upfront. “But this is what we’re left with,” he tells them.

Another big concern in the field is “the quality of data for focal therapy is overwhelmingly poor,” said Jonathan Shoag, MD, a urologic oncologist at University Hospitals and an associate professor of urology at Case Western Reserve University School of Medicine in Cleveland. “Essentially, the bulk of the data is from single-institution retrospective series without defined follow-up protocols or endpoints.”

The American Urological Association (AUA) has even cautioned experts and patients about the lack of high-quality data comparing focal therapy techniques to radiation therapy, surgery, and active surveillance. According to the AUA, focal options should only be considered in intermediate-risk prostate cancer in a clinical trial setting.

“The lack of randomized clinical trials poses a major stumbling block for the field,” said Dr. Ahmed.

Although randomized trials would be ideal, the results would take many years to mature, and growing patient demand for these less invasive focal procedures has made randomized trials difficult to complete, explained Arvin George, MD, associate professor at Johns Hopkins School of Medicine in Baltimore. Several randomized trials attempted in Norway and the United Kingdom, for instance, fell apart when patients refused to be randomized between focal and radical therapy, Dr. George said.

Focal therapy is now in the same position that active surveillance was a few years ago, according to Dr. George.

“We are hearing the same concerns about focal therapy now as we did about active surveillance,” he said. The initial evidence supporting active surveillance largely came from real-world experience and retrospective studies. The randomized data came later, and skeptics of active surveillance “were proven wrong,” he added.

But Dr. Shoag has a different take on the trajectory of focal therapy research and care in the United States. 

“I think there’s this emerging kind of tragedy happening in our field now, where you have even academic institutions offering focal therapy to patients off-trial with essentially no data to suggest it is oncologically effective,” Dr. Shoag said.

William Catalona, MD, Northwestern University Feinberg School of Medicine, Chicago, agreed, noting that too many low-risk patients are undergoing focal treatment who should be on active surveillance. “Many men are attracted to focal because they just are uncomfortable having a cancer in their body that’s not treated,” Dr. Catalona said. But “giving these patients focal therapy is really overtreatment.”

Patients with higher-risk disease who want to avoid aggressive treatment are also being lured into focal without guidelines or clear evidence to back up that option, Dr. Catalona explained.

Although it’s not clear how many men in the United States are receiving focal therapy who shouldn’t, even proponents of focal therapy, like George, have expressed concern.

Dr. George agreed that focal therapy marketing geared towards patients is drawing in some men who are not good candidates for these techniques, and feels there’s not enough objective material from medical societies or academic centers giving patients a realistic picture of focal therapy. 

“There is concern that patients may be receiving biased information,” Dr. George said, adding that it’s ultimately up to the physician to reconcile the best available evidence, understand the outcomes, and discuss these options with the patient to guide them to what’s best.

At the end of the day, Dr. Spratt said, physicians giving focal therapy off a clinical trial need to pause and ask themselves “why are they giving a treatment that remains investigational by payers, not recommended by any major guideline, and that lacks any randomized evidence?” 

Mr. LaFrate does not regret his decision to forgo focal therapy in 2013. He has been on active surveillance for about a decade now.

Following an MRI in 2022, Mr. LaFrate’s radiology report found that “clinically significant cancer is very unlikely to be present.”

Still, his PSA has risen two points in the past year to 14. His current urologist feels that the PSA is going up because there’s cancer present and is suggesting focal therapy for Mr. LaFrate.

Mr. LaFrate, who has prostate enlargement issues, remains skeptical of focal therapy and is still resisting the sales pitch.

“My doctor is not aggressively pushing it. He’s just giving me that as one of my options,” he said. “I just have a hunch I don’t need it at this point.”

A version of this article appeared on Medscape.com.

In 2013, a prostate-specific antigen (PSA) blood test revealed that Richard LaFrate’s levels had jumped. 

Previously in a normal range, his PSA was now above 6 ng/mL, indicating an elevated likelihood for prostate cancer. The jazz guitarist from Leesburg, Florida, then 70 years old, underwent a biopsy, which found two Gleason 6 lesions. 

Mr. LaFrate had low-risk prostate cancer.

Guidelines now recommend active surveillance for patients like Mr. LaFrate, who have low-risk disease. This strategy would mean monitoring the cancer until LaFrate required treatment, with the upside being he might never need therapy.

Mr. LaFrate’s urologist, however, was pushing whole gland surgery — an invasive and unnecessary procedure given his diagnosis and age. 

Mr. LaFrate decided to look for another doctor. He filled out a form online that pointed him to a new urologist who offered him one option: An investigational procedure known as high-intensity focused ultrasound.

At the time, high-intensity focused ultrasound — a form of focal therapy — was being studied in the United States to treat men with low or intermediate-risk prostate cancer, but it was still relatively early days.

Mr. LaFrate’s urologist asked him to pay $25,000 out of pocket to undergo the focal procedure at a clinic in the Bahamas. He refused and, ultimately, landed on active surveillance as the best strategy to manage for his low-risk disease.

That urologist was “a shyster in my opinion,” Mr. LaFrate said. 

Over the past 10 years, the popularity of focal therapy has grown among men with intermediate-risk prostate cancer — Gleason 3+4 (grade group 2) tumors — as an alternative to invasive surgery and active surveillance. Prestigious medical centers, such as Cleveland Clinic, Mayo Clinic, Memorial Sloan Kettering, UCLA, and the University of Chicago, routinely offer focal therapy. 

But use of the techniques remains controversial and costly.

As the Cleveland Clinic’s website acknowledges, although “the use of focal therapy for localized prostate cancer appears to be a promising development in a number of ways, it is still considered investigational and not yet part of standard therapy.” Major caveats to focal therapy include unknown long-term effectiveness, the possibility of leaving behind untreated cancer, and higher overall costs. 

No major national guidelines endorse the use of focal therapy, unless offered in a research or clinical trial setting. Insurance companies, such as Aetna, Blue Cross Blue Shield, and United, also consider focal therapy for prostate cancer investigational and don’t cover it.

Without a stamp of approval from guideline bodies and insurance companies, patients, like Mr. LaFrate, remain vulnerable to the high out-of-pocket costs for these focal techniques. 

“Almost every place charges $15,000-$30,000 in cash,” said Daniel Spratt, MD, radiation oncology chair at University Hospitals Seidman Cancer Center and Case Western Reserve University in Cleveland. 

Dr. Spratt has seen hundreds of patients after focal therapy, some from prominent centers, who have emptied their bank accounts to undergo treatment with the promise of great results and ultimately felt misled when the cancer has recurred.

“It pains me that there are doctors willing to ignore the Hippocratic oath of ‘Do No Harm’ simply to jump on this fad to bring in revenue,” Dr. Spratt said. 
 

Evidence-Based or Oversold?

Focal therapy gained a foothold in the United Kingdom well before the United States.

Hashim Ahmed, FRCS, urology chair at Imperial College London, has used focal therapy for 15 years, treated over 1000 patients, and taught dozens of surgeons how to use the leading focal therapies — focal cryoablation, in which surgeons use a needle-thin probe to target, freeze, and kill prostate tumors, as well as high-intensity focused ultrasound, which uses sound wave energy to superheat and kill tumors.

“Certainly, in the United Kingdom, focal therapy has been prime time in a number of centers for a number of years,” Dr. Ahmed said. 

In the United States, focal therapy has become an attractive option for men with prostate cancer who want to avoid radiation or radical prostatectomy but don’t feel comfortable simply monitoring their disease with active surveillance. Experts from specialized focal therapy centers touting the promise of this “innovative technique” predict its routine use in the next few years.

But the excitement surrounding the use of focal therapy in prostate cancer has outpaced broader acceptance.

In 2015, the FDA approved high-intensity focused ultrasound to treat prostatic disease, but not prostate cancer specifically. Although the approval language “means that companies cannot advertise that their devices can be used for prostate cancer,” physicians can still determine how to use the technology, which includes treating prostate cancer, Dr. Ahmed said. 

The evidence is starting to catch up to the demand. The latest research suggests that the partial-gland techniques may stand up well to radical prostatectomy.

A 2022 prospective database study comparing radical prostatectomies to focal therapy — mostly high-intensity focused ultrasound — in more than 800 men found similar rates of failure-free survival in the two groups at the 8-year follow-up. A 2019 registry study found that failure-free survival at 3 years was just over 90% in high and intermediate-risk patients receiving focal cryotherapy, with the rate rising to about 93% for the intermediate-risk group. And a 2018 prospective study of 625 patients with intermediate or high-risk prostate cancer who underwent high-intensity focused ultrasound had 5-year metastasis-free survival of 98% and overall survival rates of 100%.

One of the biggest draws of focal therapy vs more aggressive treatments is the “massive differences in side-effect profiles,” said Dr. Ahmed.

In a 2021 meta-analysis, researchers found that 6 months after high-intensity focused ultrasound, 98% of patients remained continent and 80% retained erectile function, while erectile dysfunction can occur in 30% to as many as 85% of patients following prostatectomy or radiotherapy and urinary incontinence can occur in as many as 40% of patients.

Despite these potential advantages of focal therapy, the long-term efficacy of the techniques remains uncertain.

A recent study from a team at MSK, for instance, reported that 40% of men with intermediate (grade 2) or high-risk (grade 3) disease had residual cancer following MRI-guided focused ultrasound. A 2020 prospective registry study found that almost 20% of patients undergoing high-intensity focal ultrasound required a second round following a recurrence. 

Dr. Spratt worries that patients who recur after focal therapy may go on to receive a second round — often offered at half price — and will still ultimately need surgery or radiation therapy later. By that point, however, patients may have spent as much as $45,000 — ie, $30,000 on the initial and another $15,000 on the follow-up procedure.

When patients see Dr. Spratt after a recurrence, he informs them that their side effects will be worse if he gives them radiation or surgery now vs if he had given them curative therapy upfront. “But this is what we’re left with,” he tells them.

Another big concern in the field is “the quality of data for focal therapy is overwhelmingly poor,” said Jonathan Shoag, MD, a urologic oncologist at University Hospitals and an associate professor of urology at Case Western Reserve University School of Medicine in Cleveland. “Essentially, the bulk of the data is from single-institution retrospective series without defined follow-up protocols or endpoints.”

The American Urological Association (AUA) has even cautioned experts and patients about the lack of high-quality data comparing focal therapy techniques to radiation therapy, surgery, and active surveillance. According to the AUA, focal options should only be considered in intermediate-risk prostate cancer in a clinical trial setting.

“The lack of randomized clinical trials poses a major stumbling block for the field,” said Dr. Ahmed.

Although randomized trials would be ideal, the results would take many years to mature, and growing patient demand for these less invasive focal procedures has made randomized trials difficult to complete, explained Arvin George, MD, associate professor at Johns Hopkins School of Medicine in Baltimore. Several randomized trials attempted in Norway and the United Kingdom, for instance, fell apart when patients refused to be randomized between focal and radical therapy, Dr. George said.

Focal therapy is now in the same position that active surveillance was a few years ago, according to Dr. George.

“We are hearing the same concerns about focal therapy now as we did about active surveillance,” he said. The initial evidence supporting active surveillance largely came from real-world experience and retrospective studies. The randomized data came later, and skeptics of active surveillance “were proven wrong,” he added.

But Dr. Shoag has a different take on the trajectory of focal therapy research and care in the United States. 

“I think there’s this emerging kind of tragedy happening in our field now, where you have even academic institutions offering focal therapy to patients off-trial with essentially no data to suggest it is oncologically effective,” Dr. Shoag said.

William Catalona, MD, Northwestern University Feinberg School of Medicine, Chicago, agreed, noting that too many low-risk patients are undergoing focal treatment who should be on active surveillance. “Many men are attracted to focal because they just are uncomfortable having a cancer in their body that’s not treated,” Dr. Catalona said. But “giving these patients focal therapy is really overtreatment.”

Patients with higher-risk disease who want to avoid aggressive treatment are also being lured into focal without guidelines or clear evidence to back up that option, Dr. Catalona explained.

Although it’s not clear how many men in the United States are receiving focal therapy who shouldn’t, even proponents of focal therapy, like George, have expressed concern.

Dr. George agreed that focal therapy marketing geared towards patients is drawing in some men who are not good candidates for these techniques, and feels there’s not enough objective material from medical societies or academic centers giving patients a realistic picture of focal therapy. 

“There is concern that patients may be receiving biased information,” Dr. George said, adding that it’s ultimately up to the physician to reconcile the best available evidence, understand the outcomes, and discuss these options with the patient to guide them to what’s best.

At the end of the day, Dr. Spratt said, physicians giving focal therapy off a clinical trial need to pause and ask themselves “why are they giving a treatment that remains investigational by payers, not recommended by any major guideline, and that lacks any randomized evidence?” 

Mr. LaFrate does not regret his decision to forgo focal therapy in 2013. He has been on active surveillance for about a decade now.

Following an MRI in 2022, Mr. LaFrate’s radiology report found that “clinically significant cancer is very unlikely to be present.”

Still, his PSA has risen two points in the past year to 14. His current urologist feels that the PSA is going up because there’s cancer present and is suggesting focal therapy for Mr. LaFrate.

Mr. LaFrate, who has prostate enlargement issues, remains skeptical of focal therapy and is still resisting the sales pitch.

“My doctor is not aggressively pushing it. He’s just giving me that as one of my options,” he said. “I just have a hunch I don’t need it at this point.”

A version of this article appeared on Medscape.com.

In 2013, a prostate-specific antigen (PSA) blood test revealed that Richard LaFrate’s levels had jumped. 

Previously in a normal range, his PSA was now above 6 ng/mL, indicating an elevated likelihood for prostate cancer. The jazz guitarist from Leesburg, Florida, then 70 years old, underwent a biopsy, which found two Gleason 6 lesions. 

Mr. LaFrate had low-risk prostate cancer.

Guidelines now recommend active surveillance for patients like Mr. LaFrate, who have low-risk disease. This strategy would mean monitoring the cancer until LaFrate required treatment, with the upside being he might never need therapy.

Mr. LaFrate’s urologist, however, was pushing whole gland surgery — an invasive and unnecessary procedure given his diagnosis and age. 

Mr. LaFrate decided to look for another doctor. He filled out a form online that pointed him to a new urologist who offered him one option: An investigational procedure known as high-intensity focused ultrasound.

At the time, high-intensity focused ultrasound — a form of focal therapy — was being studied in the United States to treat men with low or intermediate-risk prostate cancer, but it was still relatively early days.

Mr. LaFrate’s urologist asked him to pay $25,000 out of pocket to undergo the focal procedure at a clinic in the Bahamas. He refused and, ultimately, landed on active surveillance as the best strategy to manage for his low-risk disease.

That urologist was “a shyster in my opinion,” Mr. LaFrate said. 

Over the past 10 years, the popularity of focal therapy has grown among men with intermediate-risk prostate cancer — Gleason 3+4 (grade group 2) tumors — as an alternative to invasive surgery and active surveillance. Prestigious medical centers, such as Cleveland Clinic, Mayo Clinic, Memorial Sloan Kettering, UCLA, and the University of Chicago, routinely offer focal therapy. 

But use of the techniques remains controversial and costly.

As the Cleveland Clinic’s website acknowledges, although “the use of focal therapy for localized prostate cancer appears to be a promising development in a number of ways, it is still considered investigational and not yet part of standard therapy.” Major caveats to focal therapy include unknown long-term effectiveness, the possibility of leaving behind untreated cancer, and higher overall costs. 

No major national guidelines endorse the use of focal therapy, unless offered in a research or clinical trial setting. Insurance companies, such as Aetna, Blue Cross Blue Shield, and United, also consider focal therapy for prostate cancer investigational and don’t cover it.

Without a stamp of approval from guideline bodies and insurance companies, patients, like Mr. LaFrate, remain vulnerable to the high out-of-pocket costs for these focal techniques. 

“Almost every place charges $15,000-$30,000 in cash,” said Daniel Spratt, MD, radiation oncology chair at University Hospitals Seidman Cancer Center and Case Western Reserve University in Cleveland. 

Dr. Spratt has seen hundreds of patients after focal therapy, some from prominent centers, who have emptied their bank accounts to undergo treatment with the promise of great results and ultimately felt misled when the cancer has recurred.

“It pains me that there are doctors willing to ignore the Hippocratic oath of ‘Do No Harm’ simply to jump on this fad to bring in revenue,” Dr. Spratt said. 
 

Evidence-Based or Oversold?

Focal therapy gained a foothold in the United Kingdom well before the United States.

Hashim Ahmed, FRCS, urology chair at Imperial College London, has used focal therapy for 15 years, treated over 1000 patients, and taught dozens of surgeons how to use the leading focal therapies — focal cryoablation, in which surgeons use a needle-thin probe to target, freeze, and kill prostate tumors, as well as high-intensity focused ultrasound, which uses sound wave energy to superheat and kill tumors.

“Certainly, in the United Kingdom, focal therapy has been prime time in a number of centers for a number of years,” Dr. Ahmed said. 

In the United States, focal therapy has become an attractive option for men with prostate cancer who want to avoid radiation or radical prostatectomy but don’t feel comfortable simply monitoring their disease with active surveillance. Experts from specialized focal therapy centers touting the promise of this “innovative technique” predict its routine use in the next few years.

But the excitement surrounding the use of focal therapy in prostate cancer has outpaced broader acceptance.

In 2015, the FDA approved high-intensity focused ultrasound to treat prostatic disease, but not prostate cancer specifically. Although the approval language “means that companies cannot advertise that their devices can be used for prostate cancer,” physicians can still determine how to use the technology, which includes treating prostate cancer, Dr. Ahmed said. 

The evidence is starting to catch up to the demand. The latest research suggests that the partial-gland techniques may stand up well to radical prostatectomy.

A 2022 prospective database study comparing radical prostatectomies to focal therapy — mostly high-intensity focused ultrasound — in more than 800 men found similar rates of failure-free survival in the two groups at the 8-year follow-up. A 2019 registry study found that failure-free survival at 3 years was just over 90% in high and intermediate-risk patients receiving focal cryotherapy, with the rate rising to about 93% for the intermediate-risk group. And a 2018 prospective study of 625 patients with intermediate or high-risk prostate cancer who underwent high-intensity focused ultrasound had 5-year metastasis-free survival of 98% and overall survival rates of 100%.

One of the biggest draws of focal therapy vs more aggressive treatments is the “massive differences in side-effect profiles,” said Dr. Ahmed.

In a 2021 meta-analysis, researchers found that 6 months after high-intensity focused ultrasound, 98% of patients remained continent and 80% retained erectile function, while erectile dysfunction can occur in 30% to as many as 85% of patients following prostatectomy or radiotherapy and urinary incontinence can occur in as many as 40% of patients.

Despite these potential advantages of focal therapy, the long-term efficacy of the techniques remains uncertain.

A recent study from a team at MSK, for instance, reported that 40% of men with intermediate (grade 2) or high-risk (grade 3) disease had residual cancer following MRI-guided focused ultrasound. A 2020 prospective registry study found that almost 20% of patients undergoing high-intensity focal ultrasound required a second round following a recurrence. 

Dr. Spratt worries that patients who recur after focal therapy may go on to receive a second round — often offered at half price — and will still ultimately need surgery or radiation therapy later. By that point, however, patients may have spent as much as $45,000 — ie, $30,000 on the initial and another $15,000 on the follow-up procedure.

When patients see Dr. Spratt after a recurrence, he informs them that their side effects will be worse if he gives them radiation or surgery now vs if he had given them curative therapy upfront. “But this is what we’re left with,” he tells them.

Another big concern in the field is “the quality of data for focal therapy is overwhelmingly poor,” said Jonathan Shoag, MD, a urologic oncologist at University Hospitals and an associate professor of urology at Case Western Reserve University School of Medicine in Cleveland. “Essentially, the bulk of the data is from single-institution retrospective series without defined follow-up protocols or endpoints.”

The American Urological Association (AUA) has even cautioned experts and patients about the lack of high-quality data comparing focal therapy techniques to radiation therapy, surgery, and active surveillance. According to the AUA, focal options should only be considered in intermediate-risk prostate cancer in a clinical trial setting.

“The lack of randomized clinical trials poses a major stumbling block for the field,” said Dr. Ahmed.

Although randomized trials would be ideal, the results would take many years to mature, and growing patient demand for these less invasive focal procedures has made randomized trials difficult to complete, explained Arvin George, MD, associate professor at Johns Hopkins School of Medicine in Baltimore. Several randomized trials attempted in Norway and the United Kingdom, for instance, fell apart when patients refused to be randomized between focal and radical therapy, Dr. George said.

Focal therapy is now in the same position that active surveillance was a few years ago, according to Dr. George.

“We are hearing the same concerns about focal therapy now as we did about active surveillance,” he said. The initial evidence supporting active surveillance largely came from real-world experience and retrospective studies. The randomized data came later, and skeptics of active surveillance “were proven wrong,” he added.

But Dr. Shoag has a different take on the trajectory of focal therapy research and care in the United States. 

“I think there’s this emerging kind of tragedy happening in our field now, where you have even academic institutions offering focal therapy to patients off-trial with essentially no data to suggest it is oncologically effective,” Dr. Shoag said.

William Catalona, MD, Northwestern University Feinberg School of Medicine, Chicago, agreed, noting that too many low-risk patients are undergoing focal treatment who should be on active surveillance. “Many men are attracted to focal because they just are uncomfortable having a cancer in their body that’s not treated,” Dr. Catalona said. But “giving these patients focal therapy is really overtreatment.”

Patients with higher-risk disease who want to avoid aggressive treatment are also being lured into focal without guidelines or clear evidence to back up that option, Dr. Catalona explained.

Although it’s not clear how many men in the United States are receiving focal therapy who shouldn’t, even proponents of focal therapy, like George, have expressed concern.

Dr. George agreed that focal therapy marketing geared towards patients is drawing in some men who are not good candidates for these techniques, and feels there’s not enough objective material from medical societies or academic centers giving patients a realistic picture of focal therapy. 

“There is concern that patients may be receiving biased information,” Dr. George said, adding that it’s ultimately up to the physician to reconcile the best available evidence, understand the outcomes, and discuss these options with the patient to guide them to what’s best.

At the end of the day, Dr. Spratt said, physicians giving focal therapy off a clinical trial need to pause and ask themselves “why are they giving a treatment that remains investigational by payers, not recommended by any major guideline, and that lacks any randomized evidence?” 

Mr. LaFrate does not regret his decision to forgo focal therapy in 2013. He has been on active surveillance for about a decade now.

Following an MRI in 2022, Mr. LaFrate’s radiology report found that “clinically significant cancer is very unlikely to be present.”

Still, his PSA has risen two points in the past year to 14. His current urologist feels that the PSA is going up because there’s cancer present and is suggesting focal therapy for Mr. LaFrate.

Mr. LaFrate, who has prostate enlargement issues, remains skeptical of focal therapy and is still resisting the sales pitch.

“My doctor is not aggressively pushing it. He’s just giving me that as one of my options,” he said. “I just have a hunch I don’t need it at this point.”

A version of this article appeared on Medscape.com.

A plant-based diet, low in dairy and meat but rich in fruits, vegetables, grains, and nuts, can improve sexual and urinary health in patients treated for local prostate cancer, new research showed.

The findings, published on February 13, 2024, in the journal Cancer, bolster previous research showing plant-based diets can reduce the risk for recurrence and improve survivorship in men with prostate cancer.

“The current study shows for the first time an association between eating more plant-based food with better scores for quality of life among patients diagnosed with prostate cancer,” Stacy Loeb, MD, a urologist in the departments of Urology and Population Health at NYU Langone Health, in New York City, who led the research.

For the new study, Dr. Loeb and her colleagues looked at data from more than 3500 men with prostate cancer in the Health Professionals Follow-Up Study, an ongoing investigation begun in 1986 and sponsored by Harvard T.H. Chan School of Public Health. The dataset included more than 50,000 male dentists, pharmacists, optometrists, osteopaths, podiatrists, and veterinarians.

The median age of prostate cancer diagnosis was 68 years; 48% of patients underwent radical prostatectomy and 35% had radiation as primary therapy. None of the patients were known to have had metastatic disease.

Men in the study answered a questionnaire every 4 years about the kinds of foods they ate and in what proportions. Another survey, administered every 2 years, assessed the frequency of incontinence, difficulties maintaining an erection, and problems with bowels, energy, and mood, among many other health concerns.

Dr. Loeb and her colleagues sorted patients into quintiles based on the proportion of plant vs animal foods the men said they eat. The authors found those who consumed the most plant-based foods scored 8%-11% better in measures of sexual function than the group that consumed the least of these products.

These men also reported up to 14% better scores for urinary health, with fewer instances of incontinence, obstruction, and irritation, and up to 13% better scores in hormonal health, marked by symptoms like low energy, depression, and hot flashes.

Justin Gregg, MD, a urology researcher at the University of Texas MD Anderson Cancer Center, in Houston, Texas, whose research has found the Mediterranean diet can slow tumor progression among men with localized prostate cancer on active surveillance, called the results “not entirely surprising, as prior studies have shown associations between plant-based diet and outcomes like erectile function among men who do not have prostate cancer.”

But Kenneth Jacobsohn, MD, professor of urology and director of lifestyle medicine at the Medical College of Wisconsin, in Milwaukee, said the new findings help establish “the positive role of diet quality and plant-based diets, specifically on quality of life after prostate cancer diagnosis and treatment for men with nonmetastatic prostate cancer.”

Dr. Jacobsohn said the study was limited by its retrospective nature and the manner of the dietary assessment.

“As the authors point out, a plant-based diet may be helpful, though it’s important to keep in mind the strong data for its protective effect in terms of cardiovascular disease risk, which is very important for men who have a history of prostate cancer as many will die of cardiovascular disease,” Dr. Gregg added.

Dr. Loeb, Dr. Gregg, and Dr. Jacobsohn reported no conflicts of interest. Some of the study authors reported a variety of potential conflicts.
 

A version of this article appeared on Medscape.com .

A plant-based diet, low in dairy and meat but rich in fruits, vegetables, grains, and nuts, can improve sexual and urinary health in patients treated for local prostate cancer, new research showed.

The findings, published on February 13, 2024, in the journal Cancer, bolster previous research showing plant-based diets can reduce the risk for recurrence and improve survivorship in men with prostate cancer.

“The current study shows for the first time an association between eating more plant-based food with better scores for quality of life among patients diagnosed with prostate cancer,” Stacy Loeb, MD, a urologist in the departments of Urology and Population Health at NYU Langone Health, in New York City, who led the research.

For the new study, Dr. Loeb and her colleagues looked at data from more than 3500 men with prostate cancer in the Health Professionals Follow-Up Study, an ongoing investigation begun in 1986 and sponsored by Harvard T.H. Chan School of Public Health. The dataset included more than 50,000 male dentists, pharmacists, optometrists, osteopaths, podiatrists, and veterinarians.

The median age of prostate cancer diagnosis was 68 years; 48% of patients underwent radical prostatectomy and 35% had radiation as primary therapy. None of the patients were known to have had metastatic disease.

Men in the study answered a questionnaire every 4 years about the kinds of foods they ate and in what proportions. Another survey, administered every 2 years, assessed the frequency of incontinence, difficulties maintaining an erection, and problems with bowels, energy, and mood, among many other health concerns.

Dr. Loeb and her colleagues sorted patients into quintiles based on the proportion of plant vs animal foods the men said they eat. The authors found those who consumed the most plant-based foods scored 8%-11% better in measures of sexual function than the group that consumed the least of these products.

These men also reported up to 14% better scores for urinary health, with fewer instances of incontinence, obstruction, and irritation, and up to 13% better scores in hormonal health, marked by symptoms like low energy, depression, and hot flashes.

Justin Gregg, MD, a urology researcher at the University of Texas MD Anderson Cancer Center, in Houston, Texas, whose research has found the Mediterranean diet can slow tumor progression among men with localized prostate cancer on active surveillance, called the results “not entirely surprising, as prior studies have shown associations between plant-based diet and outcomes like erectile function among men who do not have prostate cancer.”

But Kenneth Jacobsohn, MD, professor of urology and director of lifestyle medicine at the Medical College of Wisconsin, in Milwaukee, said the new findings help establish “the positive role of diet quality and plant-based diets, specifically on quality of life after prostate cancer diagnosis and treatment for men with nonmetastatic prostate cancer.”

Dr. Jacobsohn said the study was limited by its retrospective nature and the manner of the dietary assessment.

“As the authors point out, a plant-based diet may be helpful, though it’s important to keep in mind the strong data for its protective effect in terms of cardiovascular disease risk, which is very important for men who have a history of prostate cancer as many will die of cardiovascular disease,” Dr. Gregg added.

Dr. Loeb, Dr. Gregg, and Dr. Jacobsohn reported no conflicts of interest. Some of the study authors reported a variety of potential conflicts.
 

A version of this article appeared on Medscape.com .

A plant-based diet, low in dairy and meat but rich in fruits, vegetables, grains, and nuts, can improve sexual and urinary health in patients treated for local prostate cancer, new research showed.

The findings, published on February 13, 2024, in the journal Cancer, bolster previous research showing plant-based diets can reduce the risk for recurrence and improve survivorship in men with prostate cancer.

“The current study shows for the first time an association between eating more plant-based food with better scores for quality of life among patients diagnosed with prostate cancer,” Stacy Loeb, MD, a urologist in the departments of Urology and Population Health at NYU Langone Health, in New York City, who led the research.

For the new study, Dr. Loeb and her colleagues looked at data from more than 3500 men with prostate cancer in the Health Professionals Follow-Up Study, an ongoing investigation begun in 1986 and sponsored by Harvard T.H. Chan School of Public Health. The dataset included more than 50,000 male dentists, pharmacists, optometrists, osteopaths, podiatrists, and veterinarians.

The median age of prostate cancer diagnosis was 68 years; 48% of patients underwent radical prostatectomy and 35% had radiation as primary therapy. None of the patients were known to have had metastatic disease.

Men in the study answered a questionnaire every 4 years about the kinds of foods they ate and in what proportions. Another survey, administered every 2 years, assessed the frequency of incontinence, difficulties maintaining an erection, and problems with bowels, energy, and mood, among many other health concerns.

Dr. Loeb and her colleagues sorted patients into quintiles based on the proportion of plant vs animal foods the men said they eat. The authors found those who consumed the most plant-based foods scored 8%-11% better in measures of sexual function than the group that consumed the least of these products.

These men also reported up to 14% better scores for urinary health, with fewer instances of incontinence, obstruction, and irritation, and up to 13% better scores in hormonal health, marked by symptoms like low energy, depression, and hot flashes.

Justin Gregg, MD, a urology researcher at the University of Texas MD Anderson Cancer Center, in Houston, Texas, whose research has found the Mediterranean diet can slow tumor progression among men with localized prostate cancer on active surveillance, called the results “not entirely surprising, as prior studies have shown associations between plant-based diet and outcomes like erectile function among men who do not have prostate cancer.”

But Kenneth Jacobsohn, MD, professor of urology and director of lifestyle medicine at the Medical College of Wisconsin, in Milwaukee, said the new findings help establish “the positive role of diet quality and plant-based diets, specifically on quality of life after prostate cancer diagnosis and treatment for men with nonmetastatic prostate cancer.”

Dr. Jacobsohn said the study was limited by its retrospective nature and the manner of the dietary assessment.

“As the authors point out, a plant-based diet may be helpful, though it’s important to keep in mind the strong data for its protective effect in terms of cardiovascular disease risk, which is very important for men who have a history of prostate cancer as many will die of cardiovascular disease,” Dr. Gregg added.

Dr. Loeb, Dr. Gregg, and Dr. Jacobsohn reported no conflicts of interest. Some of the study authors reported a variety of potential conflicts.
 

A version of this article appeared on Medscape.com .

Medicare will now cover the use of an AI-based test for prostate cancer that can predict which men will benefit from potentially disabling androgen deprivation therapy.

The Centers for Medicare & Medicare Services (CMS) on January 1 approved the payment rate for ArteraAI as a clinical diagnostic laboratory test. The test is the first that can both predict therapeutic benefit and prognosticate long-term outcomes in localized prostate cancer. 

Daniel Spratt, MD, chair of radiation oncology at UH Seidman Cancer Center in Cleveland, who has been involved in researching ArteraAI, told this news organization that the test improves risk stratification or prognostication over standard clinical and pathologic tools, such as prostate-specific antigen, Gleason score, and T-stage, or risk groupings such as those from the National Comprehensive Cancer Network (NCCN).

“Medicare approval allows this test to reach more patients without the financial burden of covering the test out of pocket. The test is found among other tests in NCCN guidelines as a tool to improve risk stratification and personalization of treatment,” said Dr. Spratt, who serves on the network’s prostate cancer panel.

ArteraAI combines a patient’s standard clinical and pathologic information into an algorithm, alongside a digitized image analysis of the patients’ prostate biopsy. The result is a score that estimates a patient’s risk of developing metastasis or dying from prostate cancer.

Dr. Spratt was the lead author of article last June in NEJM Evidence that validated ArteraAI. He said ArteraAI is 80% accurate as a prognostic test compared with 65% accuracy using NCCN stratification systems. 

The AI test spares about two thirds of men with intermediate-risk prostate cancer who are starting radiation therapy from androgen deprivation and its side effects, such as weight gain, breast enlargement, hot flashes, heart disease, and brain problems, Dr. Spratt added. 

Andre Esteva, CEO and co-founder of San Francisco-based ArteraAI, said, “After someone is diagnosed with localized prostate cancer, deciding on a treatment can feel very overwhelming as there are so many factors to consider. During this time, knowledge is power, and having detailed, personalized information can increase confidence when making these challenging decisions. The ArteraAI Prostate Test was developed with this in mind and can predict whether a patient will benefit from hormone therapy and estimate long-term outcomes.”

Bruno Barrey is one of Dr. Spratt’s patients. Barrey, a robotics engineer from suburban Detroit who was transitioning from active surveillance with Gleason 3+4 intermediate-risk prostate cancer to radiation therapy, said, “I was concerned about the side effects from androgen-deprivation therapy. I was relieved that the AI test allowed me to avoid hormone therapy.”

Dr. Spratt reported working with NRG Oncology, a clinical trials group funded by the National Cancer Institute, and as an academic collaborator with ArteraAI. 

A version of this article appeared on Medscape.com.

Medicare will now cover the use of an AI-based test for prostate cancer that can predict which men will benefit from potentially disabling androgen deprivation therapy.

The Centers for Medicare & Medicare Services (CMS) on January 1 approved the payment rate for ArteraAI as a clinical diagnostic laboratory test. The test is the first that can both predict therapeutic benefit and prognosticate long-term outcomes in localized prostate cancer. 

Daniel Spratt, MD, chair of radiation oncology at UH Seidman Cancer Center in Cleveland, who has been involved in researching ArteraAI, told this news organization that the test improves risk stratification or prognostication over standard clinical and pathologic tools, such as prostate-specific antigen, Gleason score, and T-stage, or risk groupings such as those from the National Comprehensive Cancer Network (NCCN).

“Medicare approval allows this test to reach more patients without the financial burden of covering the test out of pocket. The test is found among other tests in NCCN guidelines as a tool to improve risk stratification and personalization of treatment,” said Dr. Spratt, who serves on the network’s prostate cancer panel.

ArteraAI combines a patient’s standard clinical and pathologic information into an algorithm, alongside a digitized image analysis of the patients’ prostate biopsy. The result is a score that estimates a patient’s risk of developing metastasis or dying from prostate cancer.

Dr. Spratt was the lead author of article last June in NEJM Evidence that validated ArteraAI. He said ArteraAI is 80% accurate as a prognostic test compared with 65% accuracy using NCCN stratification systems. 

The AI test spares about two thirds of men with intermediate-risk prostate cancer who are starting radiation therapy from androgen deprivation and its side effects, such as weight gain, breast enlargement, hot flashes, heart disease, and brain problems, Dr. Spratt added. 

Andre Esteva, CEO and co-founder of San Francisco-based ArteraAI, said, “After someone is diagnosed with localized prostate cancer, deciding on a treatment can feel very overwhelming as there are so many factors to consider. During this time, knowledge is power, and having detailed, personalized information can increase confidence when making these challenging decisions. The ArteraAI Prostate Test was developed with this in mind and can predict whether a patient will benefit from hormone therapy and estimate long-term outcomes.”

Bruno Barrey is one of Dr. Spratt’s patients. Barrey, a robotics engineer from suburban Detroit who was transitioning from active surveillance with Gleason 3+4 intermediate-risk prostate cancer to radiation therapy, said, “I was concerned about the side effects from androgen-deprivation therapy. I was relieved that the AI test allowed me to avoid hormone therapy.”

Dr. Spratt reported working with NRG Oncology, a clinical trials group funded by the National Cancer Institute, and as an academic collaborator with ArteraAI. 

A version of this article appeared on Medscape.com.

Medicare will now cover the use of an AI-based test for prostate cancer that can predict which men will benefit from potentially disabling androgen deprivation therapy.

The Centers for Medicare & Medicare Services (CMS) on January 1 approved the payment rate for ArteraAI as a clinical diagnostic laboratory test. The test is the first that can both predict therapeutic benefit and prognosticate long-term outcomes in localized prostate cancer. 

Daniel Spratt, MD, chair of radiation oncology at UH Seidman Cancer Center in Cleveland, who has been involved in researching ArteraAI, told this news organization that the test improves risk stratification or prognostication over standard clinical and pathologic tools, such as prostate-specific antigen, Gleason score, and T-stage, or risk groupings such as those from the National Comprehensive Cancer Network (NCCN).

“Medicare approval allows this test to reach more patients without the financial burden of covering the test out of pocket. The test is found among other tests in NCCN guidelines as a tool to improve risk stratification and personalization of treatment,” said Dr. Spratt, who serves on the network’s prostate cancer panel.

ArteraAI combines a patient’s standard clinical and pathologic information into an algorithm, alongside a digitized image analysis of the patients’ prostate biopsy. The result is a score that estimates a patient’s risk of developing metastasis or dying from prostate cancer.

Dr. Spratt was the lead author of article last June in NEJM Evidence that validated ArteraAI. He said ArteraAI is 80% accurate as a prognostic test compared with 65% accuracy using NCCN stratification systems. 

The AI test spares about two thirds of men with intermediate-risk prostate cancer who are starting radiation therapy from androgen deprivation and its side effects, such as weight gain, breast enlargement, hot flashes, heart disease, and brain problems, Dr. Spratt added. 

Andre Esteva, CEO and co-founder of San Francisco-based ArteraAI, said, “After someone is diagnosed with localized prostate cancer, deciding on a treatment can feel very overwhelming as there are so many factors to consider. During this time, knowledge is power, and having detailed, personalized information can increase confidence when making these challenging decisions. The ArteraAI Prostate Test was developed with this in mind and can predict whether a patient will benefit from hormone therapy and estimate long-term outcomes.”

Bruno Barrey is one of Dr. Spratt’s patients. Barrey, a robotics engineer from suburban Detroit who was transitioning from active surveillance with Gleason 3+4 intermediate-risk prostate cancer to radiation therapy, said, “I was concerned about the side effects from androgen-deprivation therapy. I was relieved that the AI test allowed me to avoid hormone therapy.”

Dr. Spratt reported working with NRG Oncology, a clinical trials group funded by the National Cancer Institute, and as an academic collaborator with ArteraAI. 

A version of this article appeared on Medscape.com.

Seventeen years ago, Philip Segal, a retired accountant from suburban Toronto, Canada, was diagnosed with prostate cancer in a private clinic. After rejecting brachytherapy recommended by an oncologist, he went on active surveillance to watch, but not treat, the Gleason 6 (grade group 1) tumor. As he approaches his 80th birthday later this year, Mr. Segal said he plans to maintain the status quo. “It definitely brings me some peace of mind. I’d rather do that than not follow it and kick myself if there was a serious change,” he said.

Meanwhile, 2 years ago and 200 miles away in suburban Detroit, Bruno Barrey, a robotics engineer, was diagnosed with three cores of Gleason 6 and went on active surveillance.

Six months after the original diagnosis, however, Mr. Barrey, 57, underwent a follow-up biopsy. This time, all 16 cores were positive, with a mix of low-risk Gleason 6 and more advanced Gleason 3 + 4 lesions. His tumor was so large he underwent radiation therapy in 2023, ending his brief stint on the monitoring approach.

The two cases illustrate the complicated truth of active surveillance. For some men, the strategy can prove to be short-lived, perhaps 5 years or less, or a life-long approach lasting until the man dies from another cause.

Which kind of race a man will run depends on a wide range of factors: His comfort level living with a cancer, or at least a tumor that might well evolve into an aggressive malignancy, changes in his prostate-specific antigen (PSA) level and results of a magnetic resonance imaging test, the volume of his cancer, results of genetic testing of the patient himself and his lesion, and his urologist’s philosophy about surveillance. Where a patient lives matters, too, because variations in surveillance levels exist in different geographic areas, domestically and internationally.

“Active surveillance is a strategy of monitoring until it is necessary to be treated. For some people, it is very short, and for others, essentially indefinite,” said Michael Leapman, MD, clinical lead at Yale Cancer Center in New Haven, Connecticut. “While there are differences, I think they are mainly about who is the ideal patient.”

Most studies show that roughly half of men in the United States who go on active surveillance abandon it within 5 years of diagnosis. Rashid Sayyid, MD, a clinical fellow at the University of Toronto, Canada, found in a paper presented to the American Urological Association in 2022 that the number leaving active surveillance increased to nearly two thirds at 10 years.

Peter Carroll, MD, a urologist at the University of California, San Francisco, and a pioneer in the active surveillance in the late 1990s, said the major reason men abandon the strategy is because monitoring reveals the presence of a more aggressive cancer, typically a grade group 2 (Gleason 3 + 4) lesion. But other reasons include anxiety and other emotional distress and upgrades in blood levels of PSA and increases in the rating scale for MRI for the likelihood of the presence of clinically significant prostate cancer.

Laurence Klotz, MD, of the University of Toronto, Toronto, Ontario, who coined the term active surveillance strategy in 1997 and published the first studies in the early 2000s, said it is important to consider when the data on surveillance were collected.

Since 2013, when MRI began to be adopted as a surveillance modality for men with prostate cancer, the dropout rate began declining. The reason? According to Dr. Klotz, MRIs and targeted biopsies result in greater accuracy in staging the disease, determining which patients need to be biopsied, which helps some men avoid being diagnosed to begin with.

Dr. Klotz cited as an example of the emerging change a 2020 study in the Journal of Urology, which found a 24% dropout rate for surveillance at 5 years, 36% at 10 years, and 42% at 15 years in a series of 2664 grade group 1 patients on active surveillance at Memorial Sloan Kettering Cancer Center in New York City from 2000 to 2017.

Dr. Leapman cited a 2023 study in JNCI Cancer Spectrum using the National Cancer Database that found a decline in the percentage of patients who had grade group 1 in biopsies from 45% in 2010 to 25% in 2019.

“There is more judicious use of PSA testing and biopsy in individuals who are more likely to have significant prostate cancer,” Dr. Leapman told this news organization. “And MRI could also play a role by finding more high-grade cancers that would have otherwise been hidden.”

The changing statistics of prostate cancer also may reflect decreases in screening in response to a 2012 statement from the US Preventive Services Task Force advising against PSA testing. The American Cancer Society in January 2023 said that statement could be driving more diagnoses of late-stage disease, which has been surging for the first time in two decades, especially among Black men.

Dr. Sayyid said patients must be selected carefully for active surveillance. And he said urologists should not promise their active surveillance patients that they will avoid treatment. “There are numerous factors at stake that influence the ultimate outcome,” he said.

Progression of Gleason scores is estimated at 1%-2% per year, Dr. Sayyid added. When active surveillance fails in the short to medium term — 5-10 years — the reason usually is that higher-grade cancers with Gleason 3 + 4 or above were initially missed.

Dr. Sayyid said he counsels patients aged 70 years and older differently than those in their 50s, telling younger patients they are more likely to need treatment eventually than the older patients.

Factors that can affect the longevity of active surveillance include the presence or absence of germline mutations and the overall health and life expectancy and comorbidities such as heart disease and diabetes in a given patient, he said.

Urologists hold varying philosophies here, especially involving younger patients and the presence of any level of Gleason 4 cancer.

William Catalona, MD, of Northwestern University Feinberg School of Medicine in Chicago, Illinois, who developed the concept of mass screening with PSA testing, originally opposed active surveillance. In recent years, he has modified his views but still takes a more conservative approach.

“I consider active surveillance a foolish strategy or, at best, a short-term strategy for young, otherwise healthy men, especially those having any Gleason pattern 4 disease.”

“More than half will ultimately convert to active treatment, some too late, and will require multiple treatments with multiple side effects. Some will develop metastases, and some will die of prostate cancer.”

Dr. Sayyid takes a more liberal approach. “I would counsel an eligible patient considering active surveillance that at the current time, I see no strong reason why you should be subjected to treatment and the associated side effects,” he said. “And as long as your overall disease ‘state’ [the combination of grade, volume, PSA, and imaging tests] remains relatively stable, there should be no reason for us to ‘jump ship’. In my practice, another term for active surveillance is ‘active partnership’ — working together to decide if this is a sprint or a lifelong marathon.”

Dr. Carroll reported research funding from the National Institutes of Health.

A version of this article appeared on Medscape.com.

Seventeen years ago, Philip Segal, a retired accountant from suburban Toronto, Canada, was diagnosed with prostate cancer in a private clinic. After rejecting brachytherapy recommended by an oncologist, he went on active surveillance to watch, but not treat, the Gleason 6 (grade group 1) tumor. As he approaches his 80th birthday later this year, Mr. Segal said he plans to maintain the status quo. “It definitely brings me some peace of mind. I’d rather do that than not follow it and kick myself if there was a serious change,” he said.

Meanwhile, 2 years ago and 200 miles away in suburban Detroit, Bruno Barrey, a robotics engineer, was diagnosed with three cores of Gleason 6 and went on active surveillance.

Six months after the original diagnosis, however, Mr. Barrey, 57, underwent a follow-up biopsy. This time, all 16 cores were positive, with a mix of low-risk Gleason 6 and more advanced Gleason 3 + 4 lesions. His tumor was so large he underwent radiation therapy in 2023, ending his brief stint on the monitoring approach.

The two cases illustrate the complicated truth of active surveillance. For some men, the strategy can prove to be short-lived, perhaps 5 years or less, or a life-long approach lasting until the man dies from another cause.

Which kind of race a man will run depends on a wide range of factors: His comfort level living with a cancer, or at least a tumor that might well evolve into an aggressive malignancy, changes in his prostate-specific antigen (PSA) level and results of a magnetic resonance imaging test, the volume of his cancer, results of genetic testing of the patient himself and his lesion, and his urologist’s philosophy about surveillance. Where a patient lives matters, too, because variations in surveillance levels exist in different geographic areas, domestically and internationally.

“Active surveillance is a strategy of monitoring until it is necessary to be treated. For some people, it is very short, and for others, essentially indefinite,” said Michael Leapman, MD, clinical lead at Yale Cancer Center in New Haven, Connecticut. “While there are differences, I think they are mainly about who is the ideal patient.”

Most studies show that roughly half of men in the United States who go on active surveillance abandon it within 5 years of diagnosis. Rashid Sayyid, MD, a clinical fellow at the University of Toronto, Canada, found in a paper presented to the American Urological Association in 2022 that the number leaving active surveillance increased to nearly two thirds at 10 years.

Peter Carroll, MD, a urologist at the University of California, San Francisco, and a pioneer in the active surveillance in the late 1990s, said the major reason men abandon the strategy is because monitoring reveals the presence of a more aggressive cancer, typically a grade group 2 (Gleason 3 + 4) lesion. But other reasons include anxiety and other emotional distress and upgrades in blood levels of PSA and increases in the rating scale for MRI for the likelihood of the presence of clinically significant prostate cancer.

Laurence Klotz, MD, of the University of Toronto, Toronto, Ontario, who coined the term active surveillance strategy in 1997 and published the first studies in the early 2000s, said it is important to consider when the data on surveillance were collected.

Since 2013, when MRI began to be adopted as a surveillance modality for men with prostate cancer, the dropout rate began declining. The reason? According to Dr. Klotz, MRIs and targeted biopsies result in greater accuracy in staging the disease, determining which patients need to be biopsied, which helps some men avoid being diagnosed to begin with.

Dr. Klotz cited as an example of the emerging change a 2020 study in the Journal of Urology, which found a 24% dropout rate for surveillance at 5 years, 36% at 10 years, and 42% at 15 years in a series of 2664 grade group 1 patients on active surveillance at Memorial Sloan Kettering Cancer Center in New York City from 2000 to 2017.

Dr. Leapman cited a 2023 study in JNCI Cancer Spectrum using the National Cancer Database that found a decline in the percentage of patients who had grade group 1 in biopsies from 45% in 2010 to 25% in 2019.

“There is more judicious use of PSA testing and biopsy in individuals who are more likely to have significant prostate cancer,” Dr. Leapman told this news organization. “And MRI could also play a role by finding more high-grade cancers that would have otherwise been hidden.”

The changing statistics of prostate cancer also may reflect decreases in screening in response to a 2012 statement from the US Preventive Services Task Force advising against PSA testing. The American Cancer Society in January 2023 said that statement could be driving more diagnoses of late-stage disease, which has been surging for the first time in two decades, especially among Black men.

Dr. Sayyid said patients must be selected carefully for active surveillance. And he said urologists should not promise their active surveillance patients that they will avoid treatment. “There are numerous factors at stake that influence the ultimate outcome,” he said.

Progression of Gleason scores is estimated at 1%-2% per year, Dr. Sayyid added. When active surveillance fails in the short to medium term — 5-10 years — the reason usually is that higher-grade cancers with Gleason 3 + 4 or above were initially missed.

Dr. Sayyid said he counsels patients aged 70 years and older differently than those in their 50s, telling younger patients they are more likely to need treatment eventually than the older patients.

Factors that can affect the longevity of active surveillance include the presence or absence of germline mutations and the overall health and life expectancy and comorbidities such as heart disease and diabetes in a given patient, he said.

Urologists hold varying philosophies here, especially involving younger patients and the presence of any level of Gleason 4 cancer.

William Catalona, MD, of Northwestern University Feinberg School of Medicine in Chicago, Illinois, who developed the concept of mass screening with PSA testing, originally opposed active surveillance. In recent years, he has modified his views but still takes a more conservative approach.

“I consider active surveillance a foolish strategy or, at best, a short-term strategy for young, otherwise healthy men, especially those having any Gleason pattern 4 disease.”

“More than half will ultimately convert to active treatment, some too late, and will require multiple treatments with multiple side effects. Some will develop metastases, and some will die of prostate cancer.”

Dr. Sayyid takes a more liberal approach. “I would counsel an eligible patient considering active surveillance that at the current time, I see no strong reason why you should be subjected to treatment and the associated side effects,” he said. “And as long as your overall disease ‘state’ [the combination of grade, volume, PSA, and imaging tests] remains relatively stable, there should be no reason for us to ‘jump ship’. In my practice, another term for active surveillance is ‘active partnership’ — working together to decide if this is a sprint or a lifelong marathon.”

Dr. Carroll reported research funding from the National Institutes of Health.

A version of this article appeared on Medscape.com.

Seventeen years ago, Philip Segal, a retired accountant from suburban Toronto, Canada, was diagnosed with prostate cancer in a private clinic. After rejecting brachytherapy recommended by an oncologist, he went on active surveillance to watch, but not treat, the Gleason 6 (grade group 1) tumor. As he approaches his 80th birthday later this year, Mr. Segal said he plans to maintain the status quo. “It definitely brings me some peace of mind. I’d rather do that than not follow it and kick myself if there was a serious change,” he said.

Meanwhile, 2 years ago and 200 miles away in suburban Detroit, Bruno Barrey, a robotics engineer, was diagnosed with three cores of Gleason 6 and went on active surveillance.

Six months after the original diagnosis, however, Mr. Barrey, 57, underwent a follow-up biopsy. This time, all 16 cores were positive, with a mix of low-risk Gleason 6 and more advanced Gleason 3 + 4 lesions. His tumor was so large he underwent radiation therapy in 2023, ending his brief stint on the monitoring approach.

The two cases illustrate the complicated truth of active surveillance. For some men, the strategy can prove to be short-lived, perhaps 5 years or less, or a life-long approach lasting until the man dies from another cause.

Which kind of race a man will run depends on a wide range of factors: His comfort level living with a cancer, or at least a tumor that might well evolve into an aggressive malignancy, changes in his prostate-specific antigen (PSA) level and results of a magnetic resonance imaging test, the volume of his cancer, results of genetic testing of the patient himself and his lesion, and his urologist’s philosophy about surveillance. Where a patient lives matters, too, because variations in surveillance levels exist in different geographic areas, domestically and internationally.

“Active surveillance is a strategy of monitoring until it is necessary to be treated. For some people, it is very short, and for others, essentially indefinite,” said Michael Leapman, MD, clinical lead at Yale Cancer Center in New Haven, Connecticut. “While there are differences, I think they are mainly about who is the ideal patient.”

Most studies show that roughly half of men in the United States who go on active surveillance abandon it within 5 years of diagnosis. Rashid Sayyid, MD, a clinical fellow at the University of Toronto, Canada, found in a paper presented to the American Urological Association in 2022 that the number leaving active surveillance increased to nearly two thirds at 10 years.

Peter Carroll, MD, a urologist at the University of California, San Francisco, and a pioneer in the active surveillance in the late 1990s, said the major reason men abandon the strategy is because monitoring reveals the presence of a more aggressive cancer, typically a grade group 2 (Gleason 3 + 4) lesion. But other reasons include anxiety and other emotional distress and upgrades in blood levels of PSA and increases in the rating scale for MRI for the likelihood of the presence of clinically significant prostate cancer.

Laurence Klotz, MD, of the University of Toronto, Toronto, Ontario, who coined the term active surveillance strategy in 1997 and published the first studies in the early 2000s, said it is important to consider when the data on surveillance were collected.

Since 2013, when MRI began to be adopted as a surveillance modality for men with prostate cancer, the dropout rate began declining. The reason? According to Dr. Klotz, MRIs and targeted biopsies result in greater accuracy in staging the disease, determining which patients need to be biopsied, which helps some men avoid being diagnosed to begin with.

Dr. Klotz cited as an example of the emerging change a 2020 study in the Journal of Urology, which found a 24% dropout rate for surveillance at 5 years, 36% at 10 years, and 42% at 15 years in a series of 2664 grade group 1 patients on active surveillance at Memorial Sloan Kettering Cancer Center in New York City from 2000 to 2017.

Dr. Leapman cited a 2023 study in JNCI Cancer Spectrum using the National Cancer Database that found a decline in the percentage of patients who had grade group 1 in biopsies from 45% in 2010 to 25% in 2019.

“There is more judicious use of PSA testing and biopsy in individuals who are more likely to have significant prostate cancer,” Dr. Leapman told this news organization. “And MRI could also play a role by finding more high-grade cancers that would have otherwise been hidden.”

The changing statistics of prostate cancer also may reflect decreases in screening in response to a 2012 statement from the US Preventive Services Task Force advising against PSA testing. The American Cancer Society in January 2023 said that statement could be driving more diagnoses of late-stage disease, which has been surging for the first time in two decades, especially among Black men.

Dr. Sayyid said patients must be selected carefully for active surveillance. And he said urologists should not promise their active surveillance patients that they will avoid treatment. “There are numerous factors at stake that influence the ultimate outcome,” he said.

Progression of Gleason scores is estimated at 1%-2% per year, Dr. Sayyid added. When active surveillance fails in the short to medium term — 5-10 years — the reason usually is that higher-grade cancers with Gleason 3 + 4 or above were initially missed.

Dr. Sayyid said he counsels patients aged 70 years and older differently than those in their 50s, telling younger patients they are more likely to need treatment eventually than the older patients.

Factors that can affect the longevity of active surveillance include the presence or absence of germline mutations and the overall health and life expectancy and comorbidities such as heart disease and diabetes in a given patient, he said.

Urologists hold varying philosophies here, especially involving younger patients and the presence of any level of Gleason 4 cancer.

William Catalona, MD, of Northwestern University Feinberg School of Medicine in Chicago, Illinois, who developed the concept of mass screening with PSA testing, originally opposed active surveillance. In recent years, he has modified his views but still takes a more conservative approach.

“I consider active surveillance a foolish strategy or, at best, a short-term strategy for young, otherwise healthy men, especially those having any Gleason pattern 4 disease.”

“More than half will ultimately convert to active treatment, some too late, and will require multiple treatments with multiple side effects. Some will develop metastases, and some will die of prostate cancer.”

Dr. Sayyid takes a more liberal approach. “I would counsel an eligible patient considering active surveillance that at the current time, I see no strong reason why you should be subjected to treatment and the associated side effects,” he said. “And as long as your overall disease ‘state’ [the combination of grade, volume, PSA, and imaging tests] remains relatively stable, there should be no reason for us to ‘jump ship’. In my practice, another term for active surveillance is ‘active partnership’ — working together to decide if this is a sprint or a lifelong marathon.”

Dr. Carroll reported research funding from the National Institutes of Health.

A version of this article appeared on Medscape.com.

Adding enzalutamide (Xtandi) to androgen deprivation therapy (ADT) can extend metastasis-free survival (MFS) while maintaining quality of life in men with prostate cancer who have a high risk for biochemical recurrence, according to new research presented at the European Society of Medical Oncology meeting in Madrid.

At 5 years, nearly 90% of patients receiving enzalutamide plus the ADT leuprolide (multiple brands) were metastasis-free, while 80% of those receiving only enzalutamide and about 71% of those receiving only leuprolide were metastasis-free.

In a related analysis of patient-reported outcomes, investigators found that patients who received enzalutamide did not appear to have worse quality of life, compared with those treated with leuprolide alone.

“This could be a game-changer for one of the most common disease states in prostate cancer,” lead author Stephen Freedland, MD, director of the Center for Integrated Research in Cancer and Lifestyle at Cedars-Sinai Cancer, Los Angeles, said. The study was published online in the New England Journal of Medicine.

The results “confirm that in this population, as in men with more advanced stages, adding an androgen-receptor inhibitor [enzalutamide] increases the efficacy of androgen deprivation therapy,” Ana Aparicio, MD, from University of Texas MD Anderson Cancer Center, Houston, wrote in an accompanying editorial.

Standard care in this patient population relies on ADT to suppress testosterone, which would otherwise stimulate cancer cell growth. However, Dr. Freedland explained that “when you go on androgen deprivation therapy, the testosterone level in the blood is reduced but not completely eliminated. The concern is that the testosterone that remains may still be enough to stimulate tumor growth.”

Enzalutamide, an oral androgen receptor inhibitor, has already shown benefits in patients with metastases, and the current EMBARK trial explored whether the inhibitor can help men with earlier-stage disease who are at risk for metastases.

The findings from the phase 3 EMBARK trial, also published in NEJM Evidence, included 1,068 patients with prostate cancer at high-risk for biochemical recurrence. Patients, who had a median age of 69 years, spanned 244 sites across 17 countries.

Patients had a median prostate-specific antigen (PSA) doubling time of 4.9 months, with a median PSA of 5.2 ng/mL. Those with PSA doubling times of 9 months or less are considered at high-risk for biochemical recurrence and increased risk for death from prostate cancer.

Dr. Freedland and colleagues randomly assigned patients to three groups – enzalutamide 160 mg plus leuprolide every 12 weeks (n = 355), enzalutamide monotherapy (n = 355), and placebo plus leuprolide (n = 358). Patients received treatment for 38.7 months on average. 

At 5-years, 87.3% of men in the combination group were metastasis-free, compared with 80% in the monotherapy group and 71.4% in the leuprolide-only group. Compared with leuprolide alone, combining enzalutamide and leuprolide reduced the risk for metastasis or death by 58% (hazard ratio, 0.42; P < .001). And compared with enzalutamide monotherapy, the combination also significantly reduced the risk for metastasis or death, compared with leuprolide alone (HR, 0.63; P = .005).

The estimated proportion of patients free from PSA progression at 5 years was 97.4% in the combination group, 88.9% in the monotherapy group, and 70% in the leuprolide-only group.

At the time of data cutoff, 33 (9%) patients in the combination group, 42 (12%) in the monotherapy group, and 55 (15%) in the leuprolide-only group had died.

Nearly all (97%) patients experienced adverse events, most of which (86.4%) were treatment-related. Overall, 46.5% of patients in the combination group experienced a grade 3 or higher adverse event, compared with 50% in the enzalutamide monotherapy group and 42.7% in the leuprolide-only group. Clustered adverse effects occurred in 80% or more patients in all three groups, with the most common cluster combining fatigue, falls, fractures, hypertension, and musculoskeletal events.

The most common adverse events in the enzalutamide monotherapy group, occurring in at least 30% of patients, included gynecomastia, joint pain, hot flashes, and fatigue. Nipple pain and breast tenderness were also common side effects in the enzalutamide monotherapy arm – occurring in 15.3% and 14.4% of patients, respectively – compared with the combination (3.1% and 1.1%) or leuprolide-only (1.1% and 1.1%) groups.

However, Dr. Freedland explained, “our quality-of-life data show that you don’t need to sacrifice global quality of life to get these cancer benefits.”

Patient-reported outcomes from EMBARK revealed that both enzalutamide combination and monotherapy versus leuprolide alone preserved high health-related quality of life in patients with a high-risk for biochemical recurrence.

More specifically, Dr. Freedland and colleagues found no differences in the time to first clinically meaningful deterioration based on questionnaires that rated pain and functional status. Functional status measures included physical, social, and emotional well-being as well as symptom severity.

However, some differences emerged. For instance, time to confirmed clinically meaningful deterioration in physical well-being score was significantly shorter among patients receiving enzalutamide, compared with leuprolide monotherapy – 24.8 months in the combination group and 27.6 months in the enzalutamide-only group versus 49.8 months in the leuprolide-only group (HR, 1.41 and 1.35, respectively).

However, sexual activity appeared to be better preserved among patients receiving enzalutamide monotherapy, compared with leuprolide alone. The median time to confirmed clinically meaningful deterioration in sexual activity score was 5.6 months with enzalutamide monotherapy versus 3 months for leuprolide alone (HR, 0.76).

Given the slightly different side-effect profiles in the enzalutamide combination and monotherapy groups, Dr. Freedland noted that “it will be up to patients and care providers to decide which is the right choice for them. I think the important message is that both are a major step forward from the current standard of care, which is androgen deprivation therapy alone.”

Pedro Barata, MD, who was not involved in the research, also noted that “this is the first time we have seen this kind of results with a novel hormonal therapy without castration.”

Overall, “the findings of this trial confirm the benefit of adding a novel hormonal therapy such as enzalutamide earlier in the course of this disease,” said Dr. Barata, a medical oncologist and director of the Clinical Genitourinary Medical Oncology Research Program at University Hospitals Seidman Cancer Center, Cleveland.

However, he explained that many patients with “rising PSA and short doubling time are known to have metastatic disease as detected by PSMA PET and are already being offered a novel hormonal therapy combined with castration. Perhaps it will be an opportunity for men who don’t want to be castrated to be offered an anti–androgen-like enzalutamide by itself without castration in this patient population.”

Research was funded by Pfizer and Astellas Pharma, manufacturers of enzalutamide.

A version of this article first appeared on Medscape.com.

Adding enzalutamide (Xtandi) to androgen deprivation therapy (ADT) can extend metastasis-free survival (MFS) while maintaining quality of life in men with prostate cancer who have a high risk for biochemical recurrence, according to new research presented at the European Society of Medical Oncology meeting in Madrid.

At 5 years, nearly 90% of patients receiving enzalutamide plus the ADT leuprolide (multiple brands) were metastasis-free, while 80% of those receiving only enzalutamide and about 71% of those receiving only leuprolide were metastasis-free.

In a related analysis of patient-reported outcomes, investigators found that patients who received enzalutamide did not appear to have worse quality of life, compared with those treated with leuprolide alone.

“This could be a game-changer for one of the most common disease states in prostate cancer,” lead author Stephen Freedland, MD, director of the Center for Integrated Research in Cancer and Lifestyle at Cedars-Sinai Cancer, Los Angeles, said. The study was published online in the New England Journal of Medicine.

The results “confirm that in this population, as in men with more advanced stages, adding an androgen-receptor inhibitor [enzalutamide] increases the efficacy of androgen deprivation therapy,” Ana Aparicio, MD, from University of Texas MD Anderson Cancer Center, Houston, wrote in an accompanying editorial.

Standard care in this patient population relies on ADT to suppress testosterone, which would otherwise stimulate cancer cell growth. However, Dr. Freedland explained that “when you go on androgen deprivation therapy, the testosterone level in the blood is reduced but not completely eliminated. The concern is that the testosterone that remains may still be enough to stimulate tumor growth.”

Enzalutamide, an oral androgen receptor inhibitor, has already shown benefits in patients with metastases, and the current EMBARK trial explored whether the inhibitor can help men with earlier-stage disease who are at risk for metastases.

The findings from the phase 3 EMBARK trial, also published in NEJM Evidence, included 1,068 patients with prostate cancer at high-risk for biochemical recurrence. Patients, who had a median age of 69 years, spanned 244 sites across 17 countries.

Patients had a median prostate-specific antigen (PSA) doubling time of 4.9 months, with a median PSA of 5.2 ng/mL. Those with PSA doubling times of 9 months or less are considered at high-risk for biochemical recurrence and increased risk for death from prostate cancer.

Dr. Freedland and colleagues randomly assigned patients to three groups – enzalutamide 160 mg plus leuprolide every 12 weeks (n = 355), enzalutamide monotherapy (n = 355), and placebo plus leuprolide (n = 358). Patients received treatment for 38.7 months on average. 

At 5-years, 87.3% of men in the combination group were metastasis-free, compared with 80% in the monotherapy group and 71.4% in the leuprolide-only group. Compared with leuprolide alone, combining enzalutamide and leuprolide reduced the risk for metastasis or death by 58% (hazard ratio, 0.42; P < .001). And compared with enzalutamide monotherapy, the combination also significantly reduced the risk for metastasis or death, compared with leuprolide alone (HR, 0.63; P = .005).

The estimated proportion of patients free from PSA progression at 5 years was 97.4% in the combination group, 88.9% in the monotherapy group, and 70% in the leuprolide-only group.

At the time of data cutoff, 33 (9%) patients in the combination group, 42 (12%) in the monotherapy group, and 55 (15%) in the leuprolide-only group had died.

Nearly all (97%) patients experienced adverse events, most of which (86.4%) were treatment-related. Overall, 46.5% of patients in the combination group experienced a grade 3 or higher adverse event, compared with 50% in the enzalutamide monotherapy group and 42.7% in the leuprolide-only group. Clustered adverse effects occurred in 80% or more patients in all three groups, with the most common cluster combining fatigue, falls, fractures, hypertension, and musculoskeletal events.

The most common adverse events in the enzalutamide monotherapy group, occurring in at least 30% of patients, included gynecomastia, joint pain, hot flashes, and fatigue. Nipple pain and breast tenderness were also common side effects in the enzalutamide monotherapy arm – occurring in 15.3% and 14.4% of patients, respectively – compared with the combination (3.1% and 1.1%) or leuprolide-only (1.1% and 1.1%) groups.

However, Dr. Freedland explained, “our quality-of-life data show that you don’t need to sacrifice global quality of life to get these cancer benefits.”

Patient-reported outcomes from EMBARK revealed that both enzalutamide combination and monotherapy versus leuprolide alone preserved high health-related quality of life in patients with a high-risk for biochemical recurrence.

More specifically, Dr. Freedland and colleagues found no differences in the time to first clinically meaningful deterioration based on questionnaires that rated pain and functional status. Functional status measures included physical, social, and emotional well-being as well as symptom severity.

However, some differences emerged. For instance, time to confirmed clinically meaningful deterioration in physical well-being score was significantly shorter among patients receiving enzalutamide, compared with leuprolide monotherapy – 24.8 months in the combination group and 27.6 months in the enzalutamide-only group versus 49.8 months in the leuprolide-only group (HR, 1.41 and 1.35, respectively).

However, sexual activity appeared to be better preserved among patients receiving enzalutamide monotherapy, compared with leuprolide alone. The median time to confirmed clinically meaningful deterioration in sexual activity score was 5.6 months with enzalutamide monotherapy versus 3 months for leuprolide alone (HR, 0.76).

Given the slightly different side-effect profiles in the enzalutamide combination and monotherapy groups, Dr. Freedland noted that “it will be up to patients and care providers to decide which is the right choice for them. I think the important message is that both are a major step forward from the current standard of care, which is androgen deprivation therapy alone.”

Pedro Barata, MD, who was not involved in the research, also noted that “this is the first time we have seen this kind of results with a novel hormonal therapy without castration.”

Overall, “the findings of this trial confirm the benefit of adding a novel hormonal therapy such as enzalutamide earlier in the course of this disease,” said Dr. Barata, a medical oncologist and director of the Clinical Genitourinary Medical Oncology Research Program at University Hospitals Seidman Cancer Center, Cleveland.

However, he explained that many patients with “rising PSA and short doubling time are known to have metastatic disease as detected by PSMA PET and are already being offered a novel hormonal therapy combined with castration. Perhaps it will be an opportunity for men who don’t want to be castrated to be offered an anti–androgen-like enzalutamide by itself without castration in this patient population.”

Research was funded by Pfizer and Astellas Pharma, manufacturers of enzalutamide.

A version of this article first appeared on Medscape.com.

Adding enzalutamide (Xtandi) to androgen deprivation therapy (ADT) can extend metastasis-free survival (MFS) while maintaining quality of life in men with prostate cancer who have a high risk for biochemical recurrence, according to new research presented at the European Society of Medical Oncology meeting in Madrid.

At 5 years, nearly 90% of patients receiving enzalutamide plus the ADT leuprolide (multiple brands) were metastasis-free, while 80% of those receiving only enzalutamide and about 71% of those receiving only leuprolide were metastasis-free.

In a related analysis of patient-reported outcomes, investigators found that patients who received enzalutamide did not appear to have worse quality of life, compared with those treated with leuprolide alone.

“This could be a game-changer for one of the most common disease states in prostate cancer,” lead author Stephen Freedland, MD, director of the Center for Integrated Research in Cancer and Lifestyle at Cedars-Sinai Cancer, Los Angeles, said. The study was published online in the New England Journal of Medicine.

The results “confirm that in this population, as in men with more advanced stages, adding an androgen-receptor inhibitor [enzalutamide] increases the efficacy of androgen deprivation therapy,” Ana Aparicio, MD, from University of Texas MD Anderson Cancer Center, Houston, wrote in an accompanying editorial.

Standard care in this patient population relies on ADT to suppress testosterone, which would otherwise stimulate cancer cell growth. However, Dr. Freedland explained that “when you go on androgen deprivation therapy, the testosterone level in the blood is reduced but not completely eliminated. The concern is that the testosterone that remains may still be enough to stimulate tumor growth.”

Enzalutamide, an oral androgen receptor inhibitor, has already shown benefits in patients with metastases, and the current EMBARK trial explored whether the inhibitor can help men with earlier-stage disease who are at risk for metastases.

The findings from the phase 3 EMBARK trial, also published in NEJM Evidence, included 1,068 patients with prostate cancer at high-risk for biochemical recurrence. Patients, who had a median age of 69 years, spanned 244 sites across 17 countries.

Patients had a median prostate-specific antigen (PSA) doubling time of 4.9 months, with a median PSA of 5.2 ng/mL. Those with PSA doubling times of 9 months or less are considered at high-risk for biochemical recurrence and increased risk for death from prostate cancer.

Dr. Freedland and colleagues randomly assigned patients to three groups – enzalutamide 160 mg plus leuprolide every 12 weeks (n = 355), enzalutamide monotherapy (n = 355), and placebo plus leuprolide (n = 358). Patients received treatment for 38.7 months on average. 

At 5-years, 87.3% of men in the combination group were metastasis-free, compared with 80% in the monotherapy group and 71.4% in the leuprolide-only group. Compared with leuprolide alone, combining enzalutamide and leuprolide reduced the risk for metastasis or death by 58% (hazard ratio, 0.42; P < .001). And compared with enzalutamide monotherapy, the combination also significantly reduced the risk for metastasis or death, compared with leuprolide alone (HR, 0.63; P = .005).

The estimated proportion of patients free from PSA progression at 5 years was 97.4% in the combination group, 88.9% in the monotherapy group, and 70% in the leuprolide-only group.

At the time of data cutoff, 33 (9%) patients in the combination group, 42 (12%) in the monotherapy group, and 55 (15%) in the leuprolide-only group had died.

Nearly all (97%) patients experienced adverse events, most of which (86.4%) were treatment-related. Overall, 46.5% of patients in the combination group experienced a grade 3 or higher adverse event, compared with 50% in the enzalutamide monotherapy group and 42.7% in the leuprolide-only group. Clustered adverse effects occurred in 80% or more patients in all three groups, with the most common cluster combining fatigue, falls, fractures, hypertension, and musculoskeletal events.

The most common adverse events in the enzalutamide monotherapy group, occurring in at least 30% of patients, included gynecomastia, joint pain, hot flashes, and fatigue. Nipple pain and breast tenderness were also common side effects in the enzalutamide monotherapy arm – occurring in 15.3% and 14.4% of patients, respectively – compared with the combination (3.1% and 1.1%) or leuprolide-only (1.1% and 1.1%) groups.

However, Dr. Freedland explained, “our quality-of-life data show that you don’t need to sacrifice global quality of life to get these cancer benefits.”

Patient-reported outcomes from EMBARK revealed that both enzalutamide combination and monotherapy versus leuprolide alone preserved high health-related quality of life in patients with a high-risk for biochemical recurrence.

More specifically, Dr. Freedland and colleagues found no differences in the time to first clinically meaningful deterioration based on questionnaires that rated pain and functional status. Functional status measures included physical, social, and emotional well-being as well as symptom severity.

However, some differences emerged. For instance, time to confirmed clinically meaningful deterioration in physical well-being score was significantly shorter among patients receiving enzalutamide, compared with leuprolide monotherapy – 24.8 months in the combination group and 27.6 months in the enzalutamide-only group versus 49.8 months in the leuprolide-only group (HR, 1.41 and 1.35, respectively).

However, sexual activity appeared to be better preserved among patients receiving enzalutamide monotherapy, compared with leuprolide alone. The median time to confirmed clinically meaningful deterioration in sexual activity score was 5.6 months with enzalutamide monotherapy versus 3 months for leuprolide alone (HR, 0.76).

Given the slightly different side-effect profiles in the enzalutamide combination and monotherapy groups, Dr. Freedland noted that “it will be up to patients and care providers to decide which is the right choice for them. I think the important message is that both are a major step forward from the current standard of care, which is androgen deprivation therapy alone.”

Pedro Barata, MD, who was not involved in the research, also noted that “this is the first time we have seen this kind of results with a novel hormonal therapy without castration.”

Overall, “the findings of this trial confirm the benefit of adding a novel hormonal therapy such as enzalutamide earlier in the course of this disease,” said Dr. Barata, a medical oncologist and director of the Clinical Genitourinary Medical Oncology Research Program at University Hospitals Seidman Cancer Center, Cleveland.

However, he explained that many patients with “rising PSA and short doubling time are known to have metastatic disease as detected by PSMA PET and are already being offered a novel hormonal therapy combined with castration. Perhaps it will be an opportunity for men who don’t want to be castrated to be offered an anti–androgen-like enzalutamide by itself without castration in this patient population.”

Research was funded by Pfizer and Astellas Pharma, manufacturers of enzalutamide.

A version of this article first appeared on Medscape.com.