Prostate Cancer

The newly updated US Department of Veterans Affairs (VA) prostate cancer clinical pathway looks like a set of guidelines, but it’s really something unique. As attendees learned at an Association of VA Hematology/Oncology (AVAHO) regional meeting in Detroit in June, the clinical pathways are designed to point the way toward a standard ideal treatment for the majority of cases, not just to suggest a number of possible options.

“Pathways will always offer one scenario. They try to get oncologists to practice in a similar fashion so things can be managed more uniformly,” Michael M. Goodman, MD, told Federal Practitioner prior to the AVAHO meeting that was focused on prostate cancer care. Goodman is an associate professor of medicine with Atrium Health Wake Forest Baptist Medical Center and helped develop the VA genitourinary oncology pathways.

“The overall goal is not just to standardize care as much as possible but also to synthesize the best and most cost-effective practices,” Goodman said. For example, “If you have 5 different therapies, and they all have about the same efficacy and safety, and 1 is less costly than the other 4, then it would make sense to choose that.”

The VA has offered pathways for multiple types of cancer since 2021, and the pathway for prostate cancer is among the most comprehensive. The VA system updated the pathway in March 2024, is available online both via SharePoint and externally.

“It goes through the entire gamut from screening, diagnosis, and management to end of life,” Goodman explained. Multiple disciplines, from primary care and surgery to genetics and imaging, can rely on the pathway to assist decision-making.

In terms of screening, the pathway offers a flow map guiding the screening choices. In patients aged ≤ 54 years, only certain high-risk groups, such as African Americans and those with a family history of prostate cancer, should be screened. From ages 54 to 69 years, patients should be consulted as part of a shared decision making process, while screening is not recommended for patients aged ≥ 70 years.

Pathway flow maps also provide information about diagnostic standards, evaluation of the newly diagnosed, risk stratification, molecular testing, and end-of-life care.

Goodman says the pathway is now integrated into the VA electronic health record system via a template so clinicians can easily document pathway use. This allows the VA to track the use of the pathways locally, regionally, and nationally track the use of the pathways.

Clinicians are not mandated to follow every step in the pathway, but Goodman said the goal is > 80% adherence. If clinicians follow the standards, he said, “you’re considering efficacy, safety, and cost for that veteran.”

Prospective data suggests that adherence to the pathway eliminates certain disparities. African American veterans, for example, are as well-represented or even better represented than White veterans in prostate cancer care when pathways are followed.

Why might clinicians veer from the pathway? “If you’re seeing a patient who was treated in the community with drug X, but drug Y is chosen by the pathway, you can carry on with the previous care.” Alternatively, in some cases, patients may not tolerate the pathway standard, Goodman noted.

Goodman reports that he consults the pathway every day. “It’s helped standardize the care I provide to ensure there’s no gaps in how I’m treating patients.”

The newly updated US Department of Veterans Affairs (VA) prostate cancer clinical pathway looks like a set of guidelines, but it’s really something unique. As attendees learned at an Association of VA Hematology/Oncology (AVAHO) regional meeting in Detroit in June, the clinical pathways are designed to point the way toward a standard ideal treatment for the majority of cases, not just to suggest a number of possible options.

“Pathways will always offer one scenario. They try to get oncologists to practice in a similar fashion so things can be managed more uniformly,” Michael M. Goodman, MD, told Federal Practitioner prior to the AVAHO meeting that was focused on prostate cancer care. Goodman is an associate professor of medicine with Atrium Health Wake Forest Baptist Medical Center and helped develop the VA genitourinary oncology pathways.

“The overall goal is not just to standardize care as much as possible but also to synthesize the best and most cost-effective practices,” Goodman said. For example, “If you have 5 different therapies, and they all have about the same efficacy and safety, and 1 is less costly than the other 4, then it would make sense to choose that.”

The VA has offered pathways for multiple types of cancer since 2021, and the pathway for prostate cancer is among the most comprehensive. The VA system updated the pathway in March 2024, is available online both via SharePoint and externally.

“It goes through the entire gamut from screening, diagnosis, and management to end of life,” Goodman explained. Multiple disciplines, from primary care and surgery to genetics and imaging, can rely on the pathway to assist decision-making.

In terms of screening, the pathway offers a flow map guiding the screening choices. In patients aged ≤ 54 years, only certain high-risk groups, such as African Americans and those with a family history of prostate cancer, should be screened. From ages 54 to 69 years, patients should be consulted as part of a shared decision making process, while screening is not recommended for patients aged ≥ 70 years.

Pathway flow maps also provide information about diagnostic standards, evaluation of the newly diagnosed, risk stratification, molecular testing, and end-of-life care.

Goodman says the pathway is now integrated into the VA electronic health record system via a template so clinicians can easily document pathway use. This allows the VA to track the use of the pathways locally, regionally, and nationally track the use of the pathways.

Clinicians are not mandated to follow every step in the pathway, but Goodman said the goal is > 80% adherence. If clinicians follow the standards, he said, “you’re considering efficacy, safety, and cost for that veteran.”

Prospective data suggests that adherence to the pathway eliminates certain disparities. African American veterans, for example, are as well-represented or even better represented than White veterans in prostate cancer care when pathways are followed.

Why might clinicians veer from the pathway? “If you’re seeing a patient who was treated in the community with drug X, but drug Y is chosen by the pathway, you can carry on with the previous care.” Alternatively, in some cases, patients may not tolerate the pathway standard, Goodman noted.

Goodman reports that he consults the pathway every day. “It’s helped standardize the care I provide to ensure there’s no gaps in how I’m treating patients.”

The newly updated US Department of Veterans Affairs (VA) prostate cancer clinical pathway looks like a set of guidelines, but it’s really something unique. As attendees learned at an Association of VA Hematology/Oncology (AVAHO) regional meeting in Detroit in June, the clinical pathways are designed to point the way toward a standard ideal treatment for the majority of cases, not just to suggest a number of possible options.

“Pathways will always offer one scenario. They try to get oncologists to practice in a similar fashion so things can be managed more uniformly,” Michael M. Goodman, MD, told Federal Practitioner prior to the AVAHO meeting that was focused on prostate cancer care. Goodman is an associate professor of medicine with Atrium Health Wake Forest Baptist Medical Center and helped develop the VA genitourinary oncology pathways.

“The overall goal is not just to standardize care as much as possible but also to synthesize the best and most cost-effective practices,” Goodman said. For example, “If you have 5 different therapies, and they all have about the same efficacy and safety, and 1 is less costly than the other 4, then it would make sense to choose that.”

The VA has offered pathways for multiple types of cancer since 2021, and the pathway for prostate cancer is among the most comprehensive. The VA system updated the pathway in March 2024, is available online both via SharePoint and externally.

“It goes through the entire gamut from screening, diagnosis, and management to end of life,” Goodman explained. Multiple disciplines, from primary care and surgery to genetics and imaging, can rely on the pathway to assist decision-making.

In terms of screening, the pathway offers a flow map guiding the screening choices. In patients aged ≤ 54 years, only certain high-risk groups, such as African Americans and those with a family history of prostate cancer, should be screened. From ages 54 to 69 years, patients should be consulted as part of a shared decision making process, while screening is not recommended for patients aged ≥ 70 years.

Pathway flow maps also provide information about diagnostic standards, evaluation of the newly diagnosed, risk stratification, molecular testing, and end-of-life care.

Goodman says the pathway is now integrated into the VA electronic health record system via a template so clinicians can easily document pathway use. This allows the VA to track the use of the pathways locally, regionally, and nationally track the use of the pathways.

Clinicians are not mandated to follow every step in the pathway, but Goodman said the goal is > 80% adherence. If clinicians follow the standards, he said, “you’re considering efficacy, safety, and cost for that veteran.”

Prospective data suggests that adherence to the pathway eliminates certain disparities. African American veterans, for example, are as well-represented or even better represented than White veterans in prostate cancer care when pathways are followed.

Why might clinicians veer from the pathway? “If you’re seeing a patient who was treated in the community with drug X, but drug Y is chosen by the pathway, you can carry on with the previous care.” Alternatively, in some cases, patients may not tolerate the pathway standard, Goodman noted.

Goodman reports that he consults the pathway every day. “It’s helped standardize the care I provide to ensure there’s no gaps in how I’m treating patients.”

A central aim of prostate cancer treatment is to prolong survival, but trials often overlook another key goal: Improving — or at least maintaining — quality of life (QoL).

The recent American Society of Clinical Oncology (ASCO) 2024 annual meeting dedicated a session to QoL outcomes in men with prostate cancer.

The trials explored the effects of treatment suspension or intensification on health-related QoL as well as interventions to manage side effects in different patient populations.

The first presentation focused on a post hoc analysis of the phase 3 EMBARK trial, which looked at the effect of suspending treatment on health-related QoL in men with nonmetastatic disease at a high risk for biochemical recurrence.

Earlier findings from the trial, presented at ESMO in 2023, showed enzalutamide alone or in combination with androgen deprivation therapy (ADT) was associated with a significant improvement in metastasis-free survival vs placebo plus leuprolide.

The initial trial randomized 1068 patients at a high risk for biochemical recurrence to these three treatment groups and suspended therapy at week 37 if prostate-specific antigen (PSA) levels fell below 0.2 ng/mL. Patients, however, were not randomized into the treatment suspension groups. Treatment resumed if PSA levels rose to ≥ 2.0 ng/mL in patients who had undergone radical prostatectomy or ≥ 5.0 ng/mL in those who had not had surgery.

The post hoc analysis, which assessed patient-reported QoL outcomes following treatment suspension at baseline and every 12 weeks until progression, found no meaningful changes in the worst pain in the past 24 hours, as measured by the Brief Pain Inventory–Short Form.

Patients also reported no meaningful changes in total and physical well-being scores on the Functional Assessment of Cancer Therapy–Prostate (FACT-P) and on the European Quality of Life Five-Dimensions (EuroQol-5D) visual analog scale score, as well as no meaningful changes in sexual activity and urinary and bowel symptoms, based on scores from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Prostate 25 (QLQ-PR25).

Hormone treatment-related symptoms on the QLQ-PR25, however, “quickly improved but eventually began to worsen after week 97,” explained lead author Stephen J. Freedland, MD, from Cedars-Sinai Medical Center, Los Angeles, California, who presented the new findings at ASCO.

Dr. Freedland concluded that the EMBARK results show that enzalutamide, with or without ADT, improves metastasis-free survival vs leuprolide alone, without affecting global health-related QoL during treatment or after treatment suspension.

However, Channing J. Paller, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine, Baltimore, Maryland, who was not involved in the research, pointed out that “patient selection is key” when choosing therapies, given that ADT has distinct adverse effects. Comorbidities and adverse effects “must be taken into consideration to help the doctor and patient make more personalized treatment choices.”
 

Treatment Intensification and QoL

Another presentation explored health-related QoL outcomes from the phase 3 PRESTO trial.

The study examined ADT intensification in 504 patients who had high-risk biochemically relapsed nonmetastatic hormone-sensitive prostate cancer and a PSA doubling time of 9 months or less. Patients were randomized to ADT monotherapy with degarelix or leuprolide, ADT plus apalutamide, or ADT plus apalutamide, abiraterone acetate, and prednisone.

In previous data from PRESTO, the combination therapy groups both had significantly longer median PSA progression-free survival than the ADT monotherapy arm.

The latest data looked at the health-related QoL outcomes in the PRESTO population, measured using the Expanded Prostate Cancer Index Composite, the PROMIS Fatigue tool, the Hot Flash Related Daily Interference Scale, and the EuroQol-5D.

Ronald C. Chen, MD, MPH, of the University of Kansas Medical Center, Kansas City, who presented the new findings at ASCO, reported that ADT plus apalutamide improved PSA progression-free survival over ADT alone and did not meaningfully increase common treatment-related symptoms, such as hormonal symptoms, sexual dysfunction, hot flash interference, and fatigue.

However, treatment intensification with triple androgen regimen did not lead to further improvements in PSA progression-free survival but did increase the rate of serious adverse events, the time to testosterone recover, and increased hot flash interference.

PRESTO as well as EMBARK “provide a strong rationale for intensification of androgen blockade in men with high-risk biochemical recurrence after completing primary local therapy” and could even “reduce the need for subsequent treatment,” concluded Dr. Chen.
 

CBT for Managing ADT Side Effects

Up to 80% of men receiving ADT to treat prostate cancer experience night sweats and hot flashes, which are associated with sleep disturbance, anxiety, low mood, and cognitive impairments.

A third trial presented during the session looked at the impact of cognitive-behavioral therapy (CBT) on these side effects of ADT treatment.

Initial findings from the MANCAN study found that CBT delivered by a psychologist reduced the impact of hot flashes and night sweats at 6 weeks.

The MANCAN2 study assessed QoL at 6 months among 162 patients with localized or advanced prostate cancer who underwent at least 6 months of continuous ADT and who experienced more severe hot flashes and night sweats, defined as a score of ≥ 2 on the hot flashes and night sweats problem rating scale.

Study participants were randomized to CBT plus treatment as usual, or treatment as usual alone, with the intervention consisting of two CBT group sessions 4 weeks apart. Between CBT sessions, patients could refer to a booklet and CD, alongside exercises and CBT strategies.

MANCAN2 confirmed that CBT was associated with a significantly greater reduction in hot flash and night sweat scores over standard care alone at 6 weeks. Patients receiving CBT also reported better QoL, sleep, and functional status but those differences did not reach statistical significance.

By 6 months, those in the CBT group still reported better outcomes in each category, but no differences were statistically significant at this time point. Overall, however, 14% of treatment as usual alone patients discontinued ADT at 6 months vs none in the CBT arm.

“Further research is therefore needed to determine whether or not you can make this effect more durable” and to look at “the potential for CBT to support treatment compliance,” said study presenter Simon J. Crabb, PhD, MBBS, from the University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, England.
 

QoL With Radioligand Crossover

Finally, the phase 3 PSMAfore study compared ¹⁷⁷Lu-PSMA-617 with abiraterone or enzalutamide in 468 taxane-naive patients with metastatic castration-resistant prostate cancer who had progressed on a previous androgen receptor pathway inhibitor.

In earlier analyses, Karim Fizazi, MD, PhD, Institut Gustave Roussy, Université Paris-Saclay, Paris, France, reported that ¹⁷⁷Lu-PSMA-617 improved radiographic progression-free survival by 59% over androgen receptor pathway inhibitor therapy but did not lead to significant differences in overall survival.

In a new interim analysis, Dr. Fizazi and colleagues explored outcomes in patients eligible to cross over to ¹⁷⁷Lu-PSMA-617 following androgen receptor pathway inhibitor therapy. Assessments of health-related QoL revealed that ¹⁷⁷Lu-PSMA-617 led to about a 40% improvement in scores on two QoL tools — 41% with FACT-P and 39% with EuroQol-5D.

On subscales of FACT-P, Dr. Fizazi reported that ¹⁷⁷Lu-PSMA-617 was also associated with a significantly longer time to worsening in physical, functional, and emotional well-being over standard therapy. A pain inventory score indicated that ¹⁷⁷Lu-PSMA-617 led to a 31% improvement in the time to worsening pain intensity, as well as a 33% increase in the time to worsening pain interference.

With the treatment having a “favorable safety profile,” Dr. Fizazi said the results suggest ¹⁷⁷Lu-PSMA-617 is a “treatment option” for patients with metastatic castration-resistant prostate cancer who have undergone androgen receptor pathway inhibitor treatment.

MANCAN2 was funded by the UK National Institute for Health and Care Research. EMBARK was funded by Astellas Pharma and Pfizer, the codevelopers of enzalutamide. PRESTO was funded by Alliance Foundation Trials and Johnson & Johnson. PSMAfore was funded by Novartis. Dr. Freedland declared relationships with Pfizer and Astellas Pharma, among others. Paller declared relationships with AstraZeneca, Dendreon, Exelixis, Janssen Oncology, Omnitura, Lilly, and Bayer. Dr. Chen declared relationships with Astellas Pharma, Pfizer, and others. Dr. Crabb declared relationships with AstraZeneca, Bristol-Myers Squibb, Ipsen, Merck, Amgen, Amphista Therapeutics, Bayer, Janssen, MSD, Pfizer, Astex Pharmaceuticals, Clovis Oncology, and Roche. Dr. Fizazi reported relationships with Novartis, AstraZeneca, and a dozen other companies.

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

A central aim of prostate cancer treatment is to prolong survival, but trials often overlook another key goal: Improving — or at least maintaining — quality of life (QoL).

The recent American Society of Clinical Oncology (ASCO) 2024 annual meeting dedicated a session to QoL outcomes in men with prostate cancer.

The trials explored the effects of treatment suspension or intensification on health-related QoL as well as interventions to manage side effects in different patient populations.

The first presentation focused on a post hoc analysis of the phase 3 EMBARK trial, which looked at the effect of suspending treatment on health-related QoL in men with nonmetastatic disease at a high risk for biochemical recurrence.

Earlier findings from the trial, presented at ESMO in 2023, showed enzalutamide alone or in combination with androgen deprivation therapy (ADT) was associated with a significant improvement in metastasis-free survival vs placebo plus leuprolide.

The initial trial randomized 1068 patients at a high risk for biochemical recurrence to these three treatment groups and suspended therapy at week 37 if prostate-specific antigen (PSA) levels fell below 0.2 ng/mL. Patients, however, were not randomized into the treatment suspension groups. Treatment resumed if PSA levels rose to ≥ 2.0 ng/mL in patients who had undergone radical prostatectomy or ≥ 5.0 ng/mL in those who had not had surgery.

The post hoc analysis, which assessed patient-reported QoL outcomes following treatment suspension at baseline and every 12 weeks until progression, found no meaningful changes in the worst pain in the past 24 hours, as measured by the Brief Pain Inventory–Short Form.

Patients also reported no meaningful changes in total and physical well-being scores on the Functional Assessment of Cancer Therapy–Prostate (FACT-P) and on the European Quality of Life Five-Dimensions (EuroQol-5D) visual analog scale score, as well as no meaningful changes in sexual activity and urinary and bowel symptoms, based on scores from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Prostate 25 (QLQ-PR25).

Hormone treatment-related symptoms on the QLQ-PR25, however, “quickly improved but eventually began to worsen after week 97,” explained lead author Stephen J. Freedland, MD, from Cedars-Sinai Medical Center, Los Angeles, California, who presented the new findings at ASCO.

Dr. Freedland concluded that the EMBARK results show that enzalutamide, with or without ADT, improves metastasis-free survival vs leuprolide alone, without affecting global health-related QoL during treatment or after treatment suspension.

However, Channing J. Paller, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine, Baltimore, Maryland, who was not involved in the research, pointed out that “patient selection is key” when choosing therapies, given that ADT has distinct adverse effects. Comorbidities and adverse effects “must be taken into consideration to help the doctor and patient make more personalized treatment choices.”
 

Treatment Intensification and QoL

Another presentation explored health-related QoL outcomes from the phase 3 PRESTO trial.

The study examined ADT intensification in 504 patients who had high-risk biochemically relapsed nonmetastatic hormone-sensitive prostate cancer and a PSA doubling time of 9 months or less. Patients were randomized to ADT monotherapy with degarelix or leuprolide, ADT plus apalutamide, or ADT plus apalutamide, abiraterone acetate, and prednisone.

In previous data from PRESTO, the combination therapy groups both had significantly longer median PSA progression-free survival than the ADT monotherapy arm.

The latest data looked at the health-related QoL outcomes in the PRESTO population, measured using the Expanded Prostate Cancer Index Composite, the PROMIS Fatigue tool, the Hot Flash Related Daily Interference Scale, and the EuroQol-5D.

Ronald C. Chen, MD, MPH, of the University of Kansas Medical Center, Kansas City, who presented the new findings at ASCO, reported that ADT plus apalutamide improved PSA progression-free survival over ADT alone and did not meaningfully increase common treatment-related symptoms, such as hormonal symptoms, sexual dysfunction, hot flash interference, and fatigue.

However, treatment intensification with triple androgen regimen did not lead to further improvements in PSA progression-free survival but did increase the rate of serious adverse events, the time to testosterone recover, and increased hot flash interference.

PRESTO as well as EMBARK “provide a strong rationale for intensification of androgen blockade in men with high-risk biochemical recurrence after completing primary local therapy” and could even “reduce the need for subsequent treatment,” concluded Dr. Chen.
 

CBT for Managing ADT Side Effects

Up to 80% of men receiving ADT to treat prostate cancer experience night sweats and hot flashes, which are associated with sleep disturbance, anxiety, low mood, and cognitive impairments.

A third trial presented during the session looked at the impact of cognitive-behavioral therapy (CBT) on these side effects of ADT treatment.

Initial findings from the MANCAN study found that CBT delivered by a psychologist reduced the impact of hot flashes and night sweats at 6 weeks.

The MANCAN2 study assessed QoL at 6 months among 162 patients with localized or advanced prostate cancer who underwent at least 6 months of continuous ADT and who experienced more severe hot flashes and night sweats, defined as a score of ≥ 2 on the hot flashes and night sweats problem rating scale.

Study participants were randomized to CBT plus treatment as usual, or treatment as usual alone, with the intervention consisting of two CBT group sessions 4 weeks apart. Between CBT sessions, patients could refer to a booklet and CD, alongside exercises and CBT strategies.

MANCAN2 confirmed that CBT was associated with a significantly greater reduction in hot flash and night sweat scores over standard care alone at 6 weeks. Patients receiving CBT also reported better QoL, sleep, and functional status but those differences did not reach statistical significance.

By 6 months, those in the CBT group still reported better outcomes in each category, but no differences were statistically significant at this time point. Overall, however, 14% of treatment as usual alone patients discontinued ADT at 6 months vs none in the CBT arm.

“Further research is therefore needed to determine whether or not you can make this effect more durable” and to look at “the potential for CBT to support treatment compliance,” said study presenter Simon J. Crabb, PhD, MBBS, from the University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, England.
 

QoL With Radioligand Crossover

Finally, the phase 3 PSMAfore study compared ¹⁷⁷Lu-PSMA-617 with abiraterone or enzalutamide in 468 taxane-naive patients with metastatic castration-resistant prostate cancer who had progressed on a previous androgen receptor pathway inhibitor.

In earlier analyses, Karim Fizazi, MD, PhD, Institut Gustave Roussy, Université Paris-Saclay, Paris, France, reported that ¹⁷⁷Lu-PSMA-617 improved radiographic progression-free survival by 59% over androgen receptor pathway inhibitor therapy but did not lead to significant differences in overall survival.

In a new interim analysis, Dr. Fizazi and colleagues explored outcomes in patients eligible to cross over to ¹⁷⁷Lu-PSMA-617 following androgen receptor pathway inhibitor therapy. Assessments of health-related QoL revealed that ¹⁷⁷Lu-PSMA-617 led to about a 40% improvement in scores on two QoL tools — 41% with FACT-P and 39% with EuroQol-5D.

On subscales of FACT-P, Dr. Fizazi reported that ¹⁷⁷Lu-PSMA-617 was also associated with a significantly longer time to worsening in physical, functional, and emotional well-being over standard therapy. A pain inventory score indicated that ¹⁷⁷Lu-PSMA-617 led to a 31% improvement in the time to worsening pain intensity, as well as a 33% increase in the time to worsening pain interference.

With the treatment having a “favorable safety profile,” Dr. Fizazi said the results suggest ¹⁷⁷Lu-PSMA-617 is a “treatment option” for patients with metastatic castration-resistant prostate cancer who have undergone androgen receptor pathway inhibitor treatment.

MANCAN2 was funded by the UK National Institute for Health and Care Research. EMBARK was funded by Astellas Pharma and Pfizer, the codevelopers of enzalutamide. PRESTO was funded by Alliance Foundation Trials and Johnson & Johnson. PSMAfore was funded by Novartis. Dr. Freedland declared relationships with Pfizer and Astellas Pharma, among others. Paller declared relationships with AstraZeneca, Dendreon, Exelixis, Janssen Oncology, Omnitura, Lilly, and Bayer. Dr. Chen declared relationships with Astellas Pharma, Pfizer, and others. Dr. Crabb declared relationships with AstraZeneca, Bristol-Myers Squibb, Ipsen, Merck, Amgen, Amphista Therapeutics, Bayer, Janssen, MSD, Pfizer, Astex Pharmaceuticals, Clovis Oncology, and Roche. Dr. Fizazi reported relationships with Novartis, AstraZeneca, and a dozen other companies.

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

A central aim of prostate cancer treatment is to prolong survival, but trials often overlook another key goal: Improving — or at least maintaining — quality of life (QoL).

The recent American Society of Clinical Oncology (ASCO) 2024 annual meeting dedicated a session to QoL outcomes in men with prostate cancer.

The trials explored the effects of treatment suspension or intensification on health-related QoL as well as interventions to manage side effects in different patient populations.

The first presentation focused on a post hoc analysis of the phase 3 EMBARK trial, which looked at the effect of suspending treatment on health-related QoL in men with nonmetastatic disease at a high risk for biochemical recurrence.

Earlier findings from the trial, presented at ESMO in 2023, showed enzalutamide alone or in combination with androgen deprivation therapy (ADT) was associated with a significant improvement in metastasis-free survival vs placebo plus leuprolide.

The initial trial randomized 1068 patients at a high risk for biochemical recurrence to these three treatment groups and suspended therapy at week 37 if prostate-specific antigen (PSA) levels fell below 0.2 ng/mL. Patients, however, were not randomized into the treatment suspension groups. Treatment resumed if PSA levels rose to ≥ 2.0 ng/mL in patients who had undergone radical prostatectomy or ≥ 5.0 ng/mL in those who had not had surgery.

The post hoc analysis, which assessed patient-reported QoL outcomes following treatment suspension at baseline and every 12 weeks until progression, found no meaningful changes in the worst pain in the past 24 hours, as measured by the Brief Pain Inventory–Short Form.

Patients also reported no meaningful changes in total and physical well-being scores on the Functional Assessment of Cancer Therapy–Prostate (FACT-P) and on the European Quality of Life Five-Dimensions (EuroQol-5D) visual analog scale score, as well as no meaningful changes in sexual activity and urinary and bowel symptoms, based on scores from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Prostate 25 (QLQ-PR25).

Hormone treatment-related symptoms on the QLQ-PR25, however, “quickly improved but eventually began to worsen after week 97,” explained lead author Stephen J. Freedland, MD, from Cedars-Sinai Medical Center, Los Angeles, California, who presented the new findings at ASCO.

Dr. Freedland concluded that the EMBARK results show that enzalutamide, with or without ADT, improves metastasis-free survival vs leuprolide alone, without affecting global health-related QoL during treatment or after treatment suspension.

However, Channing J. Paller, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine, Baltimore, Maryland, who was not involved in the research, pointed out that “patient selection is key” when choosing therapies, given that ADT has distinct adverse effects. Comorbidities and adverse effects “must be taken into consideration to help the doctor and patient make more personalized treatment choices.”
 

Treatment Intensification and QoL

Another presentation explored health-related QoL outcomes from the phase 3 PRESTO trial.

The study examined ADT intensification in 504 patients who had high-risk biochemically relapsed nonmetastatic hormone-sensitive prostate cancer and a PSA doubling time of 9 months or less. Patients were randomized to ADT monotherapy with degarelix or leuprolide, ADT plus apalutamide, or ADT plus apalutamide, abiraterone acetate, and prednisone.

In previous data from PRESTO, the combination therapy groups both had significantly longer median PSA progression-free survival than the ADT monotherapy arm.

The latest data looked at the health-related QoL outcomes in the PRESTO population, measured using the Expanded Prostate Cancer Index Composite, the PROMIS Fatigue tool, the Hot Flash Related Daily Interference Scale, and the EuroQol-5D.

Ronald C. Chen, MD, MPH, of the University of Kansas Medical Center, Kansas City, who presented the new findings at ASCO, reported that ADT plus apalutamide improved PSA progression-free survival over ADT alone and did not meaningfully increase common treatment-related symptoms, such as hormonal symptoms, sexual dysfunction, hot flash interference, and fatigue.

However, treatment intensification with triple androgen regimen did not lead to further improvements in PSA progression-free survival but did increase the rate of serious adverse events, the time to testosterone recover, and increased hot flash interference.

PRESTO as well as EMBARK “provide a strong rationale for intensification of androgen blockade in men with high-risk biochemical recurrence after completing primary local therapy” and could even “reduce the need for subsequent treatment,” concluded Dr. Chen.
 

CBT for Managing ADT Side Effects

Up to 80% of men receiving ADT to treat prostate cancer experience night sweats and hot flashes, which are associated with sleep disturbance, anxiety, low mood, and cognitive impairments.

A third trial presented during the session looked at the impact of cognitive-behavioral therapy (CBT) on these side effects of ADT treatment.

Initial findings from the MANCAN study found that CBT delivered by a psychologist reduced the impact of hot flashes and night sweats at 6 weeks.

The MANCAN2 study assessed QoL at 6 months among 162 patients with localized or advanced prostate cancer who underwent at least 6 months of continuous ADT and who experienced more severe hot flashes and night sweats, defined as a score of ≥ 2 on the hot flashes and night sweats problem rating scale.

Study participants were randomized to CBT plus treatment as usual, or treatment as usual alone, with the intervention consisting of two CBT group sessions 4 weeks apart. Between CBT sessions, patients could refer to a booklet and CD, alongside exercises and CBT strategies.

MANCAN2 confirmed that CBT was associated with a significantly greater reduction in hot flash and night sweat scores over standard care alone at 6 weeks. Patients receiving CBT also reported better QoL, sleep, and functional status but those differences did not reach statistical significance.

By 6 months, those in the CBT group still reported better outcomes in each category, but no differences were statistically significant at this time point. Overall, however, 14% of treatment as usual alone patients discontinued ADT at 6 months vs none in the CBT arm.

“Further research is therefore needed to determine whether or not you can make this effect more durable” and to look at “the potential for CBT to support treatment compliance,” said study presenter Simon J. Crabb, PhD, MBBS, from the University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, England.
 

QoL With Radioligand Crossover

Finally, the phase 3 PSMAfore study compared ¹⁷⁷Lu-PSMA-617 with abiraterone or enzalutamide in 468 taxane-naive patients with metastatic castration-resistant prostate cancer who had progressed on a previous androgen receptor pathway inhibitor.

In earlier analyses, Karim Fizazi, MD, PhD, Institut Gustave Roussy, Université Paris-Saclay, Paris, France, reported that ¹⁷⁷Lu-PSMA-617 improved radiographic progression-free survival by 59% over androgen receptor pathway inhibitor therapy but did not lead to significant differences in overall survival.

In a new interim analysis, Dr. Fizazi and colleagues explored outcomes in patients eligible to cross over to ¹⁷⁷Lu-PSMA-617 following androgen receptor pathway inhibitor therapy. Assessments of health-related QoL revealed that ¹⁷⁷Lu-PSMA-617 led to about a 40% improvement in scores on two QoL tools — 41% with FACT-P and 39% with EuroQol-5D.

On subscales of FACT-P, Dr. Fizazi reported that ¹⁷⁷Lu-PSMA-617 was also associated with a significantly longer time to worsening in physical, functional, and emotional well-being over standard therapy. A pain inventory score indicated that ¹⁷⁷Lu-PSMA-617 led to a 31% improvement in the time to worsening pain intensity, as well as a 33% increase in the time to worsening pain interference.

With the treatment having a “favorable safety profile,” Dr. Fizazi said the results suggest ¹⁷⁷Lu-PSMA-617 is a “treatment option” for patients with metastatic castration-resistant prostate cancer who have undergone androgen receptor pathway inhibitor treatment.

MANCAN2 was funded by the UK National Institute for Health and Care Research. EMBARK was funded by Astellas Pharma and Pfizer, the codevelopers of enzalutamide. PRESTO was funded by Alliance Foundation Trials and Johnson & Johnson. PSMAfore was funded by Novartis. Dr. Freedland declared relationships with Pfizer and Astellas Pharma, among others. Paller declared relationships with AstraZeneca, Dendreon, Exelixis, Janssen Oncology, Omnitura, Lilly, and Bayer. Dr. Chen declared relationships with Astellas Pharma, Pfizer, and others. Dr. Crabb declared relationships with AstraZeneca, Bristol-Myers Squibb, Ipsen, Merck, Amgen, Amphista Therapeutics, Bayer, Janssen, MSD, Pfizer, Astex Pharmaceuticals, Clovis Oncology, and Roche. Dr. Fizazi reported relationships with Novartis, AstraZeneca, and a dozen other companies.

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

Not too long ago, prostate-cancer genetics didn’t mean much to patient care. But in recent years, the landscape of therapy has transformed as researchers have discovered links between multiple genes and aggressive tumors. 

Now, as a hematologist-oncologist explained to attendees at an Association of VA Hematology/Oncology regional meeting in Detroit, genetic tests can guide treatment for some—but not all—men with prostate cancer.

For patients with mutations, appropriate supplemental medications “can improve overall outcomes and have a long-standing impact on patients” said Scott J. Dawsey, MD, of the John D. Dingell Veterans Affairs Medical Center in Detroit in an interview following the AVAHO meeting, which focused on the management of prostate cancer.

As Dawsey explained, about 10% of patients with prostate cancer appear to have genetic mutations, although the exact percentage is unclear. The mutations are especially common in metastatic forms of prostate cancer. They’re estimated to be present in 11.8%-16.2% of those cases.

While these proportions are relatively small, the number of overall prostate-cancer cases with mutations is large due to the high burden of the disease, Dawsey said. Prostate cancer is by far the most common cancer in men, and estimated 299,010 cases will be diagnosed in the United States this year.

According to Dawsey, genetic mutations seem to boost the risk of more aggressive disease—and the risk of other malignancies—by disrupting DNA repair. This process can lead to even more mutations that may “make the cancer behave and grow more aggressively.”

But not all prostate cancer patients need to undergo genetic testing. Dawsey urged colleagues to figure out which patients should be tested by consulting National Comprehensive Cancer Network (NCCN) guidelines and the newly updated US Department of Veterans Affairs (VA) prostate cancer clinical pathway.

The two sets of recommendations agree on germline testing in patients with cases that are metastatic, very high risk, and high risk. Lower-risk cases should only be tested if patients meet family history criteria. The sets of guidelines also recommend somatic testing in patients with metastatic cancer.

In addition to providing guidance about treatment, genetic test results can have implications regarding other potential malignancies that may affect patients, Dawsey said. The results may also have implications for cancer risk in family members.

Several drugs are now available for patients with genetic mutations, including checkpoint inhibitors and PARP inhibitors. The drugs, which have unique mechanisms of action, are given in addition to standard prostate cancer treatments, he said.

“If a patient doesn’t have one of these genetic changes,” he said, “these drugs aren’t an option.”

A long list of drugs or combinations of drugs are in clinical trials, including the poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors olaparib, abiraterone, and niraparib and the checkpoint inhibitors nivolumab and cemiplimab.

The drugs generally improve response rates and progression-free survival, Dawsey said, and patients are generally able to tolerate them. In regard to which drugs to choose, he suggested consulting the and NCCN guidelines and the VA oncology clinical pathway for prostate cancer.

Not too long ago, prostate-cancer genetics didn’t mean much to patient care. But in recent years, the landscape of therapy has transformed as researchers have discovered links between multiple genes and aggressive tumors. 

Now, as a hematologist-oncologist explained to attendees at an Association of VA Hematology/Oncology regional meeting in Detroit, genetic tests can guide treatment for some—but not all—men with prostate cancer.

For patients with mutations, appropriate supplemental medications “can improve overall outcomes and have a long-standing impact on patients” said Scott J. Dawsey, MD, of the John D. Dingell Veterans Affairs Medical Center in Detroit in an interview following the AVAHO meeting, which focused on the management of prostate cancer.

As Dawsey explained, about 10% of patients with prostate cancer appear to have genetic mutations, although the exact percentage is unclear. The mutations are especially common in metastatic forms of prostate cancer. They’re estimated to be present in 11.8%-16.2% of those cases.

While these proportions are relatively small, the number of overall prostate-cancer cases with mutations is large due to the high burden of the disease, Dawsey said. Prostate cancer is by far the most common cancer in men, and estimated 299,010 cases will be diagnosed in the United States this year.

According to Dawsey, genetic mutations seem to boost the risk of more aggressive disease—and the risk of other malignancies—by disrupting DNA repair. This process can lead to even more mutations that may “make the cancer behave and grow more aggressively.”

But not all prostate cancer patients need to undergo genetic testing. Dawsey urged colleagues to figure out which patients should be tested by consulting National Comprehensive Cancer Network (NCCN) guidelines and the newly updated US Department of Veterans Affairs (VA) prostate cancer clinical pathway.

The two sets of recommendations agree on germline testing in patients with cases that are metastatic, very high risk, and high risk. Lower-risk cases should only be tested if patients meet family history criteria. The sets of guidelines also recommend somatic testing in patients with metastatic cancer.

In addition to providing guidance about treatment, genetic test results can have implications regarding other potential malignancies that may affect patients, Dawsey said. The results may also have implications for cancer risk in family members.

Several drugs are now available for patients with genetic mutations, including checkpoint inhibitors and PARP inhibitors. The drugs, which have unique mechanisms of action, are given in addition to standard prostate cancer treatments, he said.

“If a patient doesn’t have one of these genetic changes,” he said, “these drugs aren’t an option.”

A long list of drugs or combinations of drugs are in clinical trials, including the poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors olaparib, abiraterone, and niraparib and the checkpoint inhibitors nivolumab and cemiplimab.

The drugs generally improve response rates and progression-free survival, Dawsey said, and patients are generally able to tolerate them. In regard to which drugs to choose, he suggested consulting the and NCCN guidelines and the VA oncology clinical pathway for prostate cancer.

Not too long ago, prostate-cancer genetics didn’t mean much to patient care. But in recent years, the landscape of therapy has transformed as researchers have discovered links between multiple genes and aggressive tumors. 

Now, as a hematologist-oncologist explained to attendees at an Association of VA Hematology/Oncology regional meeting in Detroit, genetic tests can guide treatment for some—but not all—men with prostate cancer.

For patients with mutations, appropriate supplemental medications “can improve overall outcomes and have a long-standing impact on patients” said Scott J. Dawsey, MD, of the John D. Dingell Veterans Affairs Medical Center in Detroit in an interview following the AVAHO meeting, which focused on the management of prostate cancer.

As Dawsey explained, about 10% of patients with prostate cancer appear to have genetic mutations, although the exact percentage is unclear. The mutations are especially common in metastatic forms of prostate cancer. They’re estimated to be present in 11.8%-16.2% of those cases.

While these proportions are relatively small, the number of overall prostate-cancer cases with mutations is large due to the high burden of the disease, Dawsey said. Prostate cancer is by far the most common cancer in men, and estimated 299,010 cases will be diagnosed in the United States this year.

According to Dawsey, genetic mutations seem to boost the risk of more aggressive disease—and the risk of other malignancies—by disrupting DNA repair. This process can lead to even more mutations that may “make the cancer behave and grow more aggressively.”

But not all prostate cancer patients need to undergo genetic testing. Dawsey urged colleagues to figure out which patients should be tested by consulting National Comprehensive Cancer Network (NCCN) guidelines and the newly updated US Department of Veterans Affairs (VA) prostate cancer clinical pathway.

The two sets of recommendations agree on germline testing in patients with cases that are metastatic, very high risk, and high risk. Lower-risk cases should only be tested if patients meet family history criteria. The sets of guidelines also recommend somatic testing in patients with metastatic cancer.

In addition to providing guidance about treatment, genetic test results can have implications regarding other potential malignancies that may affect patients, Dawsey said. The results may also have implications for cancer risk in family members.

Several drugs are now available for patients with genetic mutations, including checkpoint inhibitors and PARP inhibitors. The drugs, which have unique mechanisms of action, are given in addition to standard prostate cancer treatments, he said.

“If a patient doesn’t have one of these genetic changes,” he said, “these drugs aren’t an option.”

A long list of drugs or combinations of drugs are in clinical trials, including the poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors olaparib, abiraterone, and niraparib and the checkpoint inhibitors nivolumab and cemiplimab.

The drugs generally improve response rates and progression-free survival, Dawsey said, and patients are generally able to tolerate them. In regard to which drugs to choose, he suggested consulting the and NCCN guidelines and the VA oncology clinical pathway for prostate cancer.

TOPLINE:

A new three-phase screening protocol that incorporates a PSA test, a four-kallikrein panel, and an MRI scan appears to improve the prostate cancer detection rate among men invited to participate in a single screening compared with those not invited, according to preliminary findings from the Finnish ProScreen randomized clinical trial.

METHODOLOGY:

• Prostate-specific antigen (PSA) screening is currently recommended for men in the United States starting at age 55. However, the test is controversial, in large part because it often detects prostate cancer that is not clinically relevant and may lead to overtreatment of men with low-grade disease.
• The current ProScreen trial assessed a screening intervention that aims to reduce unnecessary diagnoses of prostate cancer but still catch relevant cancers and reduce prostate cancer mortality.
• The researchers randomized 60,745 eligible men aged 50-63 years to be invited to a three-phase screening intervention (n = 15,201) or to be part of a control group that was not invited to screen (n = 45,544).
• The screening group who agreed to participate (n = 7744) first underwent a PSA test. Those with a PSA of ≥ 3.0 ng/mL then underwent a four-kallikrein panel to identify high-grade prostate cancer. Those with a kallikrein panel risk score of 7.5% or higher underwent an MRI of the prostate gland.
• Targeted biopsies were performed in those with abnormal prostate gland findings on MRI. Most patients with a negative MRI were not recommended for systematic biopsy unless they had a PSA density of ≥ 0.15 ng/mL.

TAKEAWAY:

• Among the 7744 invited men who agreed to the three-phase screening protocol (51%), ultimately 209 (2.7% of all screened participants) had a targeted transrectal prostate biopsy. Overall, 136 of the biopsies (65%) detected cancer — 32 low-grade and 128 high-grade prostate cancers, for cumulative incidence rates of 0.41% and 1.65%, respectively.
• Over a 3.2-year median follow-up among the 7457 invited men who refused screening, seven low-grade and 44 high-grade prostate cancers were detected (cumulative incidence rates, 0.1% and 0.6%, respectively).
• Among the entire invited screening group, 39 low-grade (cumulative incidence, 0.26%) and 172 high-grade prostate cancers (cumulative incidence, 1.13%) were detected.
• Among men in the control group, 65 low-grade prostate cancers were ultimately identified and 282 high-grade. The risk difference between the invited screening group and control group was 0.11% for low-grade disease and 0.51% for high-grade disease. Compared with the control group, the intervention led to the detection of one additional low-grade prostate cancer per 909 men invited to screen and one additional high-grade prostate cancer per 196 men invited.

IN PRACTICE:

The three-phase screening approach used in this study detected additional cancers, compared with a control group not invited for screening, but “these results are descriptive and should be interpreted provisionally pending results from the trial on the primary outcomes of prostate cancer mortality,” the investigators said.

SOURCE:

This study was conducted by the ProScreen Trial Investigators, including first author Anssi Auvinen, MD, PhD, of Tampere University, Tampere, Finland, and was published online in JAMAalongside an accompanying editorial.

LIMITATIONS:

Absolute differences between the two randomized groups in this study were small and had unclear clinical importance. Prior screening was reported by several participants and may have reduced cancer detection. The results are based on a single invitation for screening, meaning some high-grade cancers were likely missed; subsequent screening invitations may identify missed cancers. No data were available on cancers missed at screening, and interval cancer incidence is needed to assess sensitivity of the screening protocol used in the study.

DISCLOSURES:

The ProScreen trial is funded by grants from the Academy of Finland, the Finnish Cancer Foundation, the Jane and Aatos Erkko Foundation, the Finland State Research Funding, Helsinki University Hospital, the Sigrid Jusélius Foundation, and the Päivikki and Sakari Sohlberg Foundation. Dr. Auvinen reported having no disclosures. Multiple co-authors reported associations outside the submitted work. The full list of author disclosures is included with the full text of the article.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A new three-phase screening protocol that incorporates a PSA test, a four-kallikrein panel, and an MRI scan appears to improve the prostate cancer detection rate among men invited to participate in a single screening compared with those not invited, according to preliminary findings from the Finnish ProScreen randomized clinical trial.

METHODOLOGY:

• Prostate-specific antigen (PSA) screening is currently recommended for men in the United States starting at age 55. However, the test is controversial, in large part because it often detects prostate cancer that is not clinically relevant and may lead to overtreatment of men with low-grade disease.
• The current ProScreen trial assessed a screening intervention that aims to reduce unnecessary diagnoses of prostate cancer but still catch relevant cancers and reduce prostate cancer mortality.
• The researchers randomized 60,745 eligible men aged 50-63 years to be invited to a three-phase screening intervention (n = 15,201) or to be part of a control group that was not invited to screen (n = 45,544).
• The screening group who agreed to participate (n = 7744) first underwent a PSA test. Those with a PSA of ≥ 3.0 ng/mL then underwent a four-kallikrein panel to identify high-grade prostate cancer. Those with a kallikrein panel risk score of 7.5% or higher underwent an MRI of the prostate gland.
• Targeted biopsies were performed in those with abnormal prostate gland findings on MRI. Most patients with a negative MRI were not recommended for systematic biopsy unless they had a PSA density of ≥ 0.15 ng/mL.

TAKEAWAY:

• Among the 7744 invited men who agreed to the three-phase screening protocol (51%), ultimately 209 (2.7% of all screened participants) had a targeted transrectal prostate biopsy. Overall, 136 of the biopsies (65%) detected cancer — 32 low-grade and 128 high-grade prostate cancers, for cumulative incidence rates of 0.41% and 1.65%, respectively.
• Over a 3.2-year median follow-up among the 7457 invited men who refused screening, seven low-grade and 44 high-grade prostate cancers were detected (cumulative incidence rates, 0.1% and 0.6%, respectively).
• Among the entire invited screening group, 39 low-grade (cumulative incidence, 0.26%) and 172 high-grade prostate cancers (cumulative incidence, 1.13%) were detected.
• Among men in the control group, 65 low-grade prostate cancers were ultimately identified and 282 high-grade. The risk difference between the invited screening group and control group was 0.11% for low-grade disease and 0.51% for high-grade disease. Compared with the control group, the intervention led to the detection of one additional low-grade prostate cancer per 909 men invited to screen and one additional high-grade prostate cancer per 196 men invited.

IN PRACTICE:

The three-phase screening approach used in this study detected additional cancers, compared with a control group not invited for screening, but “these results are descriptive and should be interpreted provisionally pending results from the trial on the primary outcomes of prostate cancer mortality,” the investigators said.

SOURCE:

This study was conducted by the ProScreen Trial Investigators, including first author Anssi Auvinen, MD, PhD, of Tampere University, Tampere, Finland, and was published online in JAMAalongside an accompanying editorial.

LIMITATIONS:

Absolute differences between the two randomized groups in this study were small and had unclear clinical importance. Prior screening was reported by several participants and may have reduced cancer detection. The results are based on a single invitation for screening, meaning some high-grade cancers were likely missed; subsequent screening invitations may identify missed cancers. No data were available on cancers missed at screening, and interval cancer incidence is needed to assess sensitivity of the screening protocol used in the study.

DISCLOSURES:

The ProScreen trial is funded by grants from the Academy of Finland, the Finnish Cancer Foundation, the Jane and Aatos Erkko Foundation, the Finland State Research Funding, Helsinki University Hospital, the Sigrid Jusélius Foundation, and the Päivikki and Sakari Sohlberg Foundation. Dr. Auvinen reported having no disclosures. Multiple co-authors reported associations outside the submitted work. The full list of author disclosures is included with the full text of the article.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A new three-phase screening protocol that incorporates a PSA test, a four-kallikrein panel, and an MRI scan appears to improve the prostate cancer detection rate among men invited to participate in a single screening compared with those not invited, according to preliminary findings from the Finnish ProScreen randomized clinical trial.

METHODOLOGY:

• Prostate-specific antigen (PSA) screening is currently recommended for men in the United States starting at age 55. However, the test is controversial, in large part because it often detects prostate cancer that is not clinically relevant and may lead to overtreatment of men with low-grade disease.
• The current ProScreen trial assessed a screening intervention that aims to reduce unnecessary diagnoses of prostate cancer but still catch relevant cancers and reduce prostate cancer mortality.
• The researchers randomized 60,745 eligible men aged 50-63 years to be invited to a three-phase screening intervention (n = 15,201) or to be part of a control group that was not invited to screen (n = 45,544).
• The screening group who agreed to participate (n = 7744) first underwent a PSA test. Those with a PSA of ≥ 3.0 ng/mL then underwent a four-kallikrein panel to identify high-grade prostate cancer. Those with a kallikrein panel risk score of 7.5% or higher underwent an MRI of the prostate gland.
• Targeted biopsies were performed in those with abnormal prostate gland findings on MRI. Most patients with a negative MRI were not recommended for systematic biopsy unless they had a PSA density of ≥ 0.15 ng/mL.

TAKEAWAY:

• Among the 7744 invited men who agreed to the three-phase screening protocol (51%), ultimately 209 (2.7% of all screened participants) had a targeted transrectal prostate biopsy. Overall, 136 of the biopsies (65%) detected cancer — 32 low-grade and 128 high-grade prostate cancers, for cumulative incidence rates of 0.41% and 1.65%, respectively.
• Over a 3.2-year median follow-up among the 7457 invited men who refused screening, seven low-grade and 44 high-grade prostate cancers were detected (cumulative incidence rates, 0.1% and 0.6%, respectively).
• Among the entire invited screening group, 39 low-grade (cumulative incidence, 0.26%) and 172 high-grade prostate cancers (cumulative incidence, 1.13%) were detected.
• Among men in the control group, 65 low-grade prostate cancers were ultimately identified and 282 high-grade. The risk difference between the invited screening group and control group was 0.11% for low-grade disease and 0.51% for high-grade disease. Compared with the control group, the intervention led to the detection of one additional low-grade prostate cancer per 909 men invited to screen and one additional high-grade prostate cancer per 196 men invited.

IN PRACTICE:

The three-phase screening approach used in this study detected additional cancers, compared with a control group not invited for screening, but “these results are descriptive and should be interpreted provisionally pending results from the trial on the primary outcomes of prostate cancer mortality,” the investigators said.

SOURCE:

This study was conducted by the ProScreen Trial Investigators, including first author Anssi Auvinen, MD, PhD, of Tampere University, Tampere, Finland, and was published online in JAMAalongside an accompanying editorial.

LIMITATIONS:

Absolute differences between the two randomized groups in this study were small and had unclear clinical importance. Prior screening was reported by several participants and may have reduced cancer detection. The results are based on a single invitation for screening, meaning some high-grade cancers were likely missed; subsequent screening invitations may identify missed cancers. No data were available on cancers missed at screening, and interval cancer incidence is needed to assess sensitivity of the screening protocol used in the study.

DISCLOSURES:

The ProScreen trial is funded by grants from the Academy of Finland, the Finnish Cancer Foundation, the Jane and Aatos Erkko Foundation, the Finland State Research Funding, Helsinki University Hospital, the Sigrid Jusélius Foundation, and the Päivikki and Sakari Sohlberg Foundation. Dr. Auvinen reported having no disclosures. Multiple co-authors reported associations outside the submitted work. The full list of author disclosures is included with the full text of the article.
 

A version of this article appeared on Medscape.com.

Men with low-risk prostate cancer who go on active surveillance rather than treatment are best followed-up for more than 15 years — and perhaps indefinitely — according one of the longest studies to date to look at the issue. 

Previous studies have shown that active surveillance continued for 15 years is appropriate to identify men who progress and need treatment, but now data out to 25 years “suggest that meticulous follow-up is needed over a longer time if the chance for cure is not to be missed,” said Emmeli Palmstedt, PhD, a research student in the Department of Urology at the Sahlgrenska Academy at the University of Gothenburg, Sweden. “These data are crucial, given the long current life expectancy” of men in otherwise good health. 

Dr. Palmstedt presented the findings at the 2024 annual meeting of the European Association of Urology.

At many centers, active surveillance is a standard of care for men with low-risk prostate cancer based on a benefit-to-risk ratio that favors delayed intervention, according to Palmstedt. Several studies, including the Göteburg-1 active surveillance trial initiated at her institution, have supported follow-up for 15 years. A new set of data from Göteborg now extends to 25 years.
 

Long-Life Expectancy Justifies Extended Surveillance

The prospective Göteborg study began enrolling men with very low- or low-risk (78%) or intermediate-risk (22%) prostate cancer in 1995. In the active surveillance program, prostate-specific antigen (PSA) was measured routinely with biopsies ordered for PSA levels ≥ 2.5 ng/mL. 

In an analysis published in 2016 when 202 (43%) of 474 patients managed with active surveillance had discontinued surveillance to start treatment, the median follow-up period was 8 years. The rate of mortality associated with prostate cancer at 15 years was estimated to be 0% for men in the very low-risk group, 4% for men in the low-risk group, and 10% for those with intermediate-risk tumors. The estimates for failure-free survival at 15 years were 88%, 77%, and 40% for the very low-, low-, and intermediate-risk groups, respectively.

In the most recent follow-up, when the median age in the Göteburg-1 study was 80 years (the median age at diagnosis was 66 years), the median follow-up period was 15.1 years with a range of up to 28.1 years. In this analysis, which focused on patients with low-risk prostate cancer at baseline, discontinuations from active surveillance had climbed to 47%. Most of these men discontinued to initiate treatment, but 79 (16%) had failed acute surveillance, meaning their progression was not caught in time for curative-intent treatment, and 2% had died from prostate cancer.
 

Treatment-Free Survival Falls to 31% 

The rate of treatment-free survival, which was estimated to be 65% in the 15-year analysis published in 2016, had declined to 31%. The rate of failure-free survival was 59%, and prostate cancer-specific survival was 92%, according to the researchers. 

While Dr. Palmstedt did not separate out her data for very low- and low-risk patients, she noted that deaths from prostate cancer among all low-risk patients climbed fourfold (8% vs 2%) since the 2016 figures were published. The proportion of men no longer failure-free climbed from 10% to more than 40%. 

“These are non-negligible numbers,” said Dr. Palmstedt, who added that overall survival fell from 69% at 15 years to 37% at 25 years.

Although some men between the 15-year and 25-year timepoints were switched to watchful waiting, these data have not yet been analyzed.

The low rate of deaths from prostate cancer over the extended period is reassuring, Dr. Palmstedt said, but the main message from the new study is that active surveillance permits curative-intent treatment to be offered even after late follow-up. She emphasized that patients without progression by 15 years cannot be considered “safe.”

Based on these data, “men with a long remaining life expectancy should be informed that active surveillance is still viable after 15 years,” Dr. Palmstedt said.
 

Active Surveillance Now More Common

Over the past decade, the proportion of men with prostate cancer managed with active surveillance has been rising steadily, according to Matthew R. Cooperberg, MD, MPH, professor of urology at the University of California, San Francisco. In a study published last year in JAMA Network Open, Dr. Cooperberg and his colleagues reported that rates of active surveillance rose from 26.5% in 2014 to 59.6% in 2021. However, given the value of the approach for avoiding overtreatment of men with low-risk prostate cancers, even that increase is not enough, he said.

“The window of opportunity for cure is typically very wide,” Dr. Cooperberg said. Although many men “will never need treatment ... long-term surveillance is definitely important” for those that do, he said. The data from trials like Göteborg-1 support the principle that this strategy still preserves the option of treatment when it is needed. 

“Treatment for cure at age 70 is generally far preferable to treatment at 55, and surveillance should absolutely be preferred treatment for the vast majority of men with low-grade disease at diagnosis,” he explained.

Dr. Palmstedt reported no potential conflicts of interest. Dr. Cooperberg reported financial relationships with Astellas, AstraZeneca, Bayer, Dendreon, Exact Sciences, Janssen, Merck, Pfizer, and Verana Health. 
 

A version of this article appeared on Medscape.com.

Men with low-risk prostate cancer who go on active surveillance rather than treatment are best followed-up for more than 15 years — and perhaps indefinitely — according one of the longest studies to date to look at the issue. 

Previous studies have shown that active surveillance continued for 15 years is appropriate to identify men who progress and need treatment, but now data out to 25 years “suggest that meticulous follow-up is needed over a longer time if the chance for cure is not to be missed,” said Emmeli Palmstedt, PhD, a research student in the Department of Urology at the Sahlgrenska Academy at the University of Gothenburg, Sweden. “These data are crucial, given the long current life expectancy” of men in otherwise good health. 

Dr. Palmstedt presented the findings at the 2024 annual meeting of the European Association of Urology.

At many centers, active surveillance is a standard of care for men with low-risk prostate cancer based on a benefit-to-risk ratio that favors delayed intervention, according to Palmstedt. Several studies, including the Göteburg-1 active surveillance trial initiated at her institution, have supported follow-up for 15 years. A new set of data from Göteborg now extends to 25 years.
 

Long-Life Expectancy Justifies Extended Surveillance

The prospective Göteborg study began enrolling men with very low- or low-risk (78%) or intermediate-risk (22%) prostate cancer in 1995. In the active surveillance program, prostate-specific antigen (PSA) was measured routinely with biopsies ordered for PSA levels ≥ 2.5 ng/mL. 

In an analysis published in 2016 when 202 (43%) of 474 patients managed with active surveillance had discontinued surveillance to start treatment, the median follow-up period was 8 years. The rate of mortality associated with prostate cancer at 15 years was estimated to be 0% for men in the very low-risk group, 4% for men in the low-risk group, and 10% for those with intermediate-risk tumors. The estimates for failure-free survival at 15 years were 88%, 77%, and 40% for the very low-, low-, and intermediate-risk groups, respectively.

In the most recent follow-up, when the median age in the Göteburg-1 study was 80 years (the median age at diagnosis was 66 years), the median follow-up period was 15.1 years with a range of up to 28.1 years. In this analysis, which focused on patients with low-risk prostate cancer at baseline, discontinuations from active surveillance had climbed to 47%. Most of these men discontinued to initiate treatment, but 79 (16%) had failed acute surveillance, meaning their progression was not caught in time for curative-intent treatment, and 2% had died from prostate cancer.
 

Treatment-Free Survival Falls to 31% 

The rate of treatment-free survival, which was estimated to be 65% in the 15-year analysis published in 2016, had declined to 31%. The rate of failure-free survival was 59%, and prostate cancer-specific survival was 92%, according to the researchers. 

While Dr. Palmstedt did not separate out her data for very low- and low-risk patients, she noted that deaths from prostate cancer among all low-risk patients climbed fourfold (8% vs 2%) since the 2016 figures were published. The proportion of men no longer failure-free climbed from 10% to more than 40%. 

“These are non-negligible numbers,” said Dr. Palmstedt, who added that overall survival fell from 69% at 15 years to 37% at 25 years.

Although some men between the 15-year and 25-year timepoints were switched to watchful waiting, these data have not yet been analyzed.

The low rate of deaths from prostate cancer over the extended period is reassuring, Dr. Palmstedt said, but the main message from the new study is that active surveillance permits curative-intent treatment to be offered even after late follow-up. She emphasized that patients without progression by 15 years cannot be considered “safe.”

Based on these data, “men with a long remaining life expectancy should be informed that active surveillance is still viable after 15 years,” Dr. Palmstedt said.
 

Active Surveillance Now More Common

Over the past decade, the proportion of men with prostate cancer managed with active surveillance has been rising steadily, according to Matthew R. Cooperberg, MD, MPH, professor of urology at the University of California, San Francisco. In a study published last year in JAMA Network Open, Dr. Cooperberg and his colleagues reported that rates of active surveillance rose from 26.5% in 2014 to 59.6% in 2021. However, given the value of the approach for avoiding overtreatment of men with low-risk prostate cancers, even that increase is not enough, he said.

“The window of opportunity for cure is typically very wide,” Dr. Cooperberg said. Although many men “will never need treatment ... long-term surveillance is definitely important” for those that do, he said. The data from trials like Göteborg-1 support the principle that this strategy still preserves the option of treatment when it is needed. 

“Treatment for cure at age 70 is generally far preferable to treatment at 55, and surveillance should absolutely be preferred treatment for the vast majority of men with low-grade disease at diagnosis,” he explained.

Dr. Palmstedt reported no potential conflicts of interest. Dr. Cooperberg reported financial relationships with Astellas, AstraZeneca, Bayer, Dendreon, Exact Sciences, Janssen, Merck, Pfizer, and Verana Health. 
 

A version of this article appeared on Medscape.com.

Men with low-risk prostate cancer who go on active surveillance rather than treatment are best followed-up for more than 15 years — and perhaps indefinitely — according one of the longest studies to date to look at the issue. 

Previous studies have shown that active surveillance continued for 15 years is appropriate to identify men who progress and need treatment, but now data out to 25 years “suggest that meticulous follow-up is needed over a longer time if the chance for cure is not to be missed,” said Emmeli Palmstedt, PhD, a research student in the Department of Urology at the Sahlgrenska Academy at the University of Gothenburg, Sweden. “These data are crucial, given the long current life expectancy” of men in otherwise good health. 

Dr. Palmstedt presented the findings at the 2024 annual meeting of the European Association of Urology.

At many centers, active surveillance is a standard of care for men with low-risk prostate cancer based on a benefit-to-risk ratio that favors delayed intervention, according to Palmstedt. Several studies, including the Göteburg-1 active surveillance trial initiated at her institution, have supported follow-up for 15 years. A new set of data from Göteborg now extends to 25 years.
 

Long-Life Expectancy Justifies Extended Surveillance

The prospective Göteborg study began enrolling men with very low- or low-risk (78%) or intermediate-risk (22%) prostate cancer in 1995. In the active surveillance program, prostate-specific antigen (PSA) was measured routinely with biopsies ordered for PSA levels ≥ 2.5 ng/mL. 

In an analysis published in 2016 when 202 (43%) of 474 patients managed with active surveillance had discontinued surveillance to start treatment, the median follow-up period was 8 years. The rate of mortality associated with prostate cancer at 15 years was estimated to be 0% for men in the very low-risk group, 4% for men in the low-risk group, and 10% for those with intermediate-risk tumors. The estimates for failure-free survival at 15 years were 88%, 77%, and 40% for the very low-, low-, and intermediate-risk groups, respectively.

In the most recent follow-up, when the median age in the Göteburg-1 study was 80 years (the median age at diagnosis was 66 years), the median follow-up period was 15.1 years with a range of up to 28.1 years. In this analysis, which focused on patients with low-risk prostate cancer at baseline, discontinuations from active surveillance had climbed to 47%. Most of these men discontinued to initiate treatment, but 79 (16%) had failed acute surveillance, meaning their progression was not caught in time for curative-intent treatment, and 2% had died from prostate cancer.
 

Treatment-Free Survival Falls to 31% 

The rate of treatment-free survival, which was estimated to be 65% in the 15-year analysis published in 2016, had declined to 31%. The rate of failure-free survival was 59%, and prostate cancer-specific survival was 92%, according to the researchers. 

While Dr. Palmstedt did not separate out her data for very low- and low-risk patients, she noted that deaths from prostate cancer among all low-risk patients climbed fourfold (8% vs 2%) since the 2016 figures were published. The proportion of men no longer failure-free climbed from 10% to more than 40%. 

“These are non-negligible numbers,” said Dr. Palmstedt, who added that overall survival fell from 69% at 15 years to 37% at 25 years.

Although some men between the 15-year and 25-year timepoints were switched to watchful waiting, these data have not yet been analyzed.

The low rate of deaths from prostate cancer over the extended period is reassuring, Dr. Palmstedt said, but the main message from the new study is that active surveillance permits curative-intent treatment to be offered even after late follow-up. She emphasized that patients without progression by 15 years cannot be considered “safe.”

Based on these data, “men with a long remaining life expectancy should be informed that active surveillance is still viable after 15 years,” Dr. Palmstedt said.
 

Active Surveillance Now More Common

Over the past decade, the proportion of men with prostate cancer managed with active surveillance has been rising steadily, according to Matthew R. Cooperberg, MD, MPH, professor of urology at the University of California, San Francisco. In a study published last year in JAMA Network Open, Dr. Cooperberg and his colleagues reported that rates of active surveillance rose from 26.5% in 2014 to 59.6% in 2021. However, given the value of the approach for avoiding overtreatment of men with low-risk prostate cancers, even that increase is not enough, he said.

“The window of opportunity for cure is typically very wide,” Dr. Cooperberg said. Although many men “will never need treatment ... long-term surveillance is definitely important” for those that do, he said. The data from trials like Göteborg-1 support the principle that this strategy still preserves the option of treatment when it is needed. 

“Treatment for cure at age 70 is generally far preferable to treatment at 55, and surveillance should absolutely be preferred treatment for the vast majority of men with low-grade disease at diagnosis,” he explained.

Dr. Palmstedt reported no potential conflicts of interest. Dr. Cooperberg reported financial relationships with Astellas, AstraZeneca, Bayer, Dendreon, Exact Sciences, Janssen, Merck, Pfizer, and Verana Health. 
 

A version of this article appeared on Medscape.com.

Rachel S. Rubin, MD: Welcome to another episode of Sex Matters. I’m Dr. Rachel Rubin. I’m a urologist and sexual medicine specialist based in the Washington, DC area, and I interview amazingly cool people doing research in sexual medicine.

I heard an incredible lecture while I was at the Mayo Clinic urology conference by Dr. Stacy Loeb, who is a wonderful researcher of all things prostate cancer and men’s health, who is now talking more plant-based diets. Her lecture was so good, I begged her to join me for this discussion.

Dr. Loeb, I would love for you to introduce yourself.

Stacy Loeb, MD: I’m Dr. Loeb. I’m a urologist at New York University in the Manhattan VA, and I recently became board certified in lifestyle medicine because it’s so important for sexual health and, really, everything that we do.

Dr. Rubin: You recently became very interested in studying plant-based diets. How did that start, and how has the research evolved over time?

Dr. Loeb: It’s really amazing. For one thing, more of our patients with prostate cancer die of heart disease than of prostate cancer. And erectile dysfunction is really an early warning sign of cardiovascular disease. We felt like it was incumbent upon us, even within urology and sexual medicine, to better understand the basis for lifestyle modification that can help with these issues. We started doing some research on it, looking at men who follow more plant-based diets, and we found that they have a lower risk for fatal prostate cancer and are less likely to have erectile dysfunction.

Dr. Rubin: Tell us more about what you found for erectile dysfunction. How much benefit do people get by switching to a plant-based diet?

Dr. Loeb: First we looked at erectile function in men without prostate cancer in the health professionals follow-up study, a very large cohort study out of Harvard University. We found that among omnivorous people, those who ate more plant-based and less animal-based food were less likely to have incident erectile dysfunction. Then, we published a new paper looking at patients with prostate cancer. These men have extra challenges for sexual function because in addition to the standard cardiovascular changes with aging, prostate cancer treatment can affect the nerves that are involved in erections. But amazingly, even in that population, we found that the men who ate more plant-based and less animal-based food had better scores for erectile function.

That was really good news, and it’s a win-win. There is no reason not to counsel our patients to eat more plant-based foods. Meat is not masculine. Meat is associated with a higher risk for erectile dysfunction and is considered carcinogenic. It’s just something that we should try to stay away from.

Dr. Rubin: How do you counsel patients who might not be ready to go fully plant-based? Is a little better than nothing? How do you even start these conversations with people? Do you have any tips for primary care doctors?

Dr. Loeb: Great question. A little bit is very much better than nothing. In fact, in the health professionals follow-up study, we actually looked at quintiles of people who ate the most meat and animal-based foods and the least plant-based foods all the way up to the most plant-based and the least animal-based diets. Along that spectrum, it really does make a big difference. Anywhere that patients can start from is definitely better than nothing.

Simple things such as Meatless Monday or choosing a few days that they will give up animal-based foods will help. For some people, trying new things is easier than cutting things out, for example, trying a milk substitute such as oat, almond, or soy milk instead of dairy milk. That could be a great first step, or trying some dishes that don’t include meat — maybe a tofu stir fry or a taco or burrito without the meat.

There are many great options out there. In terms of resources for doctors, the Physicians Committee for Responsible Medicine has a great website. They have fact sheets for a lot of the common questions that people ask such as how can I get enough protein or calcium on a plant-based diet? This isn’t a problem at all. In fact, Novak Djokovic and many other elite athletes eat plant-based diets, and they get enough protein with a much higher requirement than most of us who are not elite athletes. These fact sheets explain which plant foods are the best

I also like Nutritionfacts.org. They also have all kinds of great videos and resources. Both of these websites have recipes that were created by doctors and nutritionists.

We can suggest that our patients work with a nutritionist or join a virtual program. For example, Plant Powered here in New York has virtual plant-based jumpstart programs. People around the country can get in on programs that have nutritionists and health coaches — for people who want a boost.

Dr. Rubin: The data are really compelling. When you were speaking, not a person in the room was interested in having a steak that night for dinner, even with a steakhouse in the hotel.

What do you say to men who have prostate cancer or suffer from erectile dysfunction? Do any data show that by going plant-based you may show improvements? We have recent studies that show that regular exercise might be as good as Viagra.

Dr. Loeb: It’s definitely not too late, even if you’ve already been diagnosed with these conditions. In my own practice, I have seen changes in patients. In fact, one of the case scenarios that I submitted for the lifestyle medicine boards was a patient who adopted a whole food, plant-based diet and no longer uses Viagra. This is definitely something that’s possible to do with intensive lifestyle modification.

Dr. Rubin: Maybe vegetables are the new sexual health aide. How can people find out more? I know you have a Sirius XM radio show.

Dr. Loeb: It’s the Men’s Health Show on Sirius XM channel 110. It’s on Wednesdays from 6:00 to 8:00 PM ET, or you can listen to it on demand anytime through the Sirius XM app.

Dr. Rubin: You have done an enormous amount of research in prostate cancer and sexual medicine. You are an all-star in the field. Thank you for sharing all of your knowledge about plant-based diets. You’ve given us all a lot to think about today.

Dr. Rubin has disclosed the following relevant financial relationships: Serve(d) as a speaker for Sprout; received research grant from Maternal Medical; received income in an amount equal to or greater than $250 from Absorption Pharmaceuticals, GSK, and Endo.

A version of this article appeared on Medscape.com.

Rachel S. Rubin, MD: Welcome to another episode of Sex Matters. I’m Dr. Rachel Rubin. I’m a urologist and sexual medicine specialist based in the Washington, DC area, and I interview amazingly cool people doing research in sexual medicine.

I heard an incredible lecture while I was at the Mayo Clinic urology conference by Dr. Stacy Loeb, who is a wonderful researcher of all things prostate cancer and men’s health, who is now talking more plant-based diets. Her lecture was so good, I begged her to join me for this discussion.

Dr. Loeb, I would love for you to introduce yourself.

Stacy Loeb, MD: I’m Dr. Loeb. I’m a urologist at New York University in the Manhattan VA, and I recently became board certified in lifestyle medicine because it’s so important for sexual health and, really, everything that we do.

Dr. Rubin: You recently became very interested in studying plant-based diets. How did that start, and how has the research evolved over time?

Dr. Loeb: It’s really amazing. For one thing, more of our patients with prostate cancer die of heart disease than of prostate cancer. And erectile dysfunction is really an early warning sign of cardiovascular disease. We felt like it was incumbent upon us, even within urology and sexual medicine, to better understand the basis for lifestyle modification that can help with these issues. We started doing some research on it, looking at men who follow more plant-based diets, and we found that they have a lower risk for fatal prostate cancer and are less likely to have erectile dysfunction.

Dr. Rubin: Tell us more about what you found for erectile dysfunction. How much benefit do people get by switching to a plant-based diet?

Dr. Loeb: First we looked at erectile function in men without prostate cancer in the health professionals follow-up study, a very large cohort study out of Harvard University. We found that among omnivorous people, those who ate more plant-based and less animal-based food were less likely to have incident erectile dysfunction. Then, we published a new paper looking at patients with prostate cancer. These men have extra challenges for sexual function because in addition to the standard cardiovascular changes with aging, prostate cancer treatment can affect the nerves that are involved in erections. But amazingly, even in that population, we found that the men who ate more plant-based and less animal-based food had better scores for erectile function.

That was really good news, and it’s a win-win. There is no reason not to counsel our patients to eat more plant-based foods. Meat is not masculine. Meat is associated with a higher risk for erectile dysfunction and is considered carcinogenic. It’s just something that we should try to stay away from.

Dr. Rubin: How do you counsel patients who might not be ready to go fully plant-based? Is a little better than nothing? How do you even start these conversations with people? Do you have any tips for primary care doctors?

Dr. Loeb: Great question. A little bit is very much better than nothing. In fact, in the health professionals follow-up study, we actually looked at quintiles of people who ate the most meat and animal-based foods and the least plant-based foods all the way up to the most plant-based and the least animal-based diets. Along that spectrum, it really does make a big difference. Anywhere that patients can start from is definitely better than nothing.

Simple things such as Meatless Monday or choosing a few days that they will give up animal-based foods will help. For some people, trying new things is easier than cutting things out, for example, trying a milk substitute such as oat, almond, or soy milk instead of dairy milk. That could be a great first step, or trying some dishes that don’t include meat — maybe a tofu stir fry or a taco or burrito without the meat.

There are many great options out there. In terms of resources for doctors, the Physicians Committee for Responsible Medicine has a great website. They have fact sheets for a lot of the common questions that people ask such as how can I get enough protein or calcium on a plant-based diet? This isn’t a problem at all. In fact, Novak Djokovic and many other elite athletes eat plant-based diets, and they get enough protein with a much higher requirement than most of us who are not elite athletes. These fact sheets explain which plant foods are the best

I also like Nutritionfacts.org. They also have all kinds of great videos and resources. Both of these websites have recipes that were created by doctors and nutritionists.

We can suggest that our patients work with a nutritionist or join a virtual program. For example, Plant Powered here in New York has virtual plant-based jumpstart programs. People around the country can get in on programs that have nutritionists and health coaches — for people who want a boost.

Dr. Rubin: The data are really compelling. When you were speaking, not a person in the room was interested in having a steak that night for dinner, even with a steakhouse in the hotel.

What do you say to men who have prostate cancer or suffer from erectile dysfunction? Do any data show that by going plant-based you may show improvements? We have recent studies that show that regular exercise might be as good as Viagra.

Dr. Loeb: It’s definitely not too late, even if you’ve already been diagnosed with these conditions. In my own practice, I have seen changes in patients. In fact, one of the case scenarios that I submitted for the lifestyle medicine boards was a patient who adopted a whole food, plant-based diet and no longer uses Viagra. This is definitely something that’s possible to do with intensive lifestyle modification.

Dr. Rubin: Maybe vegetables are the new sexual health aide. How can people find out more? I know you have a Sirius XM radio show.

Dr. Loeb: It’s the Men’s Health Show on Sirius XM channel 110. It’s on Wednesdays from 6:00 to 8:00 PM ET, or you can listen to it on demand anytime through the Sirius XM app.

Dr. Rubin: You have done an enormous amount of research in prostate cancer and sexual medicine. You are an all-star in the field. Thank you for sharing all of your knowledge about plant-based diets. You’ve given us all a lot to think about today.

Dr. Rubin has disclosed the following relevant financial relationships: Serve(d) as a speaker for Sprout; received research grant from Maternal Medical; received income in an amount equal to or greater than $250 from Absorption Pharmaceuticals, GSK, and Endo.

A version of this article appeared on Medscape.com.

Rachel S. Rubin, MD: Welcome to another episode of Sex Matters. I’m Dr. Rachel Rubin. I’m a urologist and sexual medicine specialist based in the Washington, DC area, and I interview amazingly cool people doing research in sexual medicine.

I heard an incredible lecture while I was at the Mayo Clinic urology conference by Dr. Stacy Loeb, who is a wonderful researcher of all things prostate cancer and men’s health, who is now talking more plant-based diets. Her lecture was so good, I begged her to join me for this discussion.

Dr. Loeb, I would love for you to introduce yourself.

Stacy Loeb, MD: I’m Dr. Loeb. I’m a urologist at New York University in the Manhattan VA, and I recently became board certified in lifestyle medicine because it’s so important for sexual health and, really, everything that we do.

Dr. Rubin: You recently became very interested in studying plant-based diets. How did that start, and how has the research evolved over time?

Dr. Loeb: It’s really amazing. For one thing, more of our patients with prostate cancer die of heart disease than of prostate cancer. And erectile dysfunction is really an early warning sign of cardiovascular disease. We felt like it was incumbent upon us, even within urology and sexual medicine, to better understand the basis for lifestyle modification that can help with these issues. We started doing some research on it, looking at men who follow more plant-based diets, and we found that they have a lower risk for fatal prostate cancer and are less likely to have erectile dysfunction.

Dr. Rubin: Tell us more about what you found for erectile dysfunction. How much benefit do people get by switching to a plant-based diet?

Dr. Loeb: First we looked at erectile function in men without prostate cancer in the health professionals follow-up study, a very large cohort study out of Harvard University. We found that among omnivorous people, those who ate more plant-based and less animal-based food were less likely to have incident erectile dysfunction. Then, we published a new paper looking at patients with prostate cancer. These men have extra challenges for sexual function because in addition to the standard cardiovascular changes with aging, prostate cancer treatment can affect the nerves that are involved in erections. But amazingly, even in that population, we found that the men who ate more plant-based and less animal-based food had better scores for erectile function.

That was really good news, and it’s a win-win. There is no reason not to counsel our patients to eat more plant-based foods. Meat is not masculine. Meat is associated with a higher risk for erectile dysfunction and is considered carcinogenic. It’s just something that we should try to stay away from.

Dr. Rubin: How do you counsel patients who might not be ready to go fully plant-based? Is a little better than nothing? How do you even start these conversations with people? Do you have any tips for primary care doctors?

Dr. Loeb: Great question. A little bit is very much better than nothing. In fact, in the health professionals follow-up study, we actually looked at quintiles of people who ate the most meat and animal-based foods and the least plant-based foods all the way up to the most plant-based and the least animal-based diets. Along that spectrum, it really does make a big difference. Anywhere that patients can start from is definitely better than nothing.

Simple things such as Meatless Monday or choosing a few days that they will give up animal-based foods will help. For some people, trying new things is easier than cutting things out, for example, trying a milk substitute such as oat, almond, or soy milk instead of dairy milk. That could be a great first step, or trying some dishes that don’t include meat — maybe a tofu stir fry or a taco or burrito without the meat.

There are many great options out there. In terms of resources for doctors, the Physicians Committee for Responsible Medicine has a great website. They have fact sheets for a lot of the common questions that people ask such as how can I get enough protein or calcium on a plant-based diet? This isn’t a problem at all. In fact, Novak Djokovic and many other elite athletes eat plant-based diets, and they get enough protein with a much higher requirement than most of us who are not elite athletes. These fact sheets explain which plant foods are the best

I also like Nutritionfacts.org. They also have all kinds of great videos and resources. Both of these websites have recipes that were created by doctors and nutritionists.

We can suggest that our patients work with a nutritionist or join a virtual program. For example, Plant Powered here in New York has virtual plant-based jumpstart programs. People around the country can get in on programs that have nutritionists and health coaches — for people who want a boost.

Dr. Rubin: The data are really compelling. When you were speaking, not a person in the room was interested in having a steak that night for dinner, even with a steakhouse in the hotel.

What do you say to men who have prostate cancer or suffer from erectile dysfunction? Do any data show that by going plant-based you may show improvements? We have recent studies that show that regular exercise might be as good as Viagra.

Dr. Loeb: It’s definitely not too late, even if you’ve already been diagnosed with these conditions. In my own practice, I have seen changes in patients. In fact, one of the case scenarios that I submitted for the lifestyle medicine boards was a patient who adopted a whole food, plant-based diet and no longer uses Viagra. This is definitely something that’s possible to do with intensive lifestyle modification.

Dr. Rubin: Maybe vegetables are the new sexual health aide. How can people find out more? I know you have a Sirius XM radio show.

Dr. Loeb: It’s the Men’s Health Show on Sirius XM channel 110. It’s on Wednesdays from 6:00 to 8:00 PM ET, or you can listen to it on demand anytime through the Sirius XM app.

Dr. Rubin: You have done an enormous amount of research in prostate cancer and sexual medicine. You are an all-star in the field. Thank you for sharing all of your knowledge about plant-based diets. You’ve given us all a lot to think about today.

Dr. Rubin has disclosed the following relevant financial relationships: Serve(d) as a speaker for Sprout; received research grant from Maternal Medical; received income in an amount equal to or greater than $250 from Absorption Pharmaceuticals, GSK, and Endo.

A version of this article appeared on Medscape.com.

SAN DIEGO — A novel multicancer early detection (MCED) blood test has demonstrated promising real-world results in detecting new cancers, including several cases of early-stage disease.

This was the conclusion of recent data presented by Ora Karp Gordon, MD, MS, during a session at the American Association for Cancer Research annual meeting.

The MCED test, known as Galleri, was made clinically available in the United States in April 2021. Developed by GRAIL LLC, the test analyzes cell-free DNA in the blood using targeted methylation analysis and machine learning to detect the presence of a cancer signal and determine its organ of origin or cancer signal origin. The initial screening of over 53,000 individuals with the Galleri test detected a cancer signal in 1.1% of participants.

The new real-world analysis examines the outcomes of repeat MCED testing in 5,794 individuals.

The study looked at individuals who initially received a ‘no cancer signal detected’ result and then underwent a second Galleri test. Over 80% of participants received their follow-up test 10-18 months after the first, with a median interval between blood draws of 12.9 months.

“The repeat tests detect those cancer cases that have reached the detection threshold since their last MCED test, which should be less than one year of incidence,” Dr. Gordon, professor at Saint John’s Cancer Institute, Santa Monica, California, said in an interview. “We are just now starting to see results from patients who get their second and even third round of screening.”

“Galleri is recommended to be used annually in addition to USPSTF [US Preventive Services Task Force]–recommended cancer screening tests, like mammography and colonoscopy,” she said.

This recommendation is based on a modeling study suggesting that annual screening would improve stage shift, diagnostic yield, and potentially mortality when compared to biennial screening, although biennial screening was still favorable compared with no screening, she explained.
 

Early Real-World Evidence of Repeat Testing

Among the cohort of 5,794 individuals who received repeat testing, 26 received a positive cancer signal on their second test, yielding a cancer signal detection rate of 0.45% (95% CI: 0.31%-0.66%). The cancer signal detection rate was slightly higher in men. The rate was 0.50% (95% CI: 0.32%-0.81%; 17 of 3367) in men versus 0.37% (95% CI: 0.2%-0.7%; 9 of 2427) in women.

During her presentation, Dr. Gordon highlighted that the repeat testing signal detection rate was lower than the initial 0.95% rate (95% CI: 0.87-1.0; 510 of 53,744) seen in the previous larger cohort of patients who were retested at 1 year.

She acknowledged that the lower cancer signal detection rate of repeat testing may indicate some degree of ‘early adopter’ bias, where those who return for a second test are systematically different from the general screening population. This could suggest that broader population-level screening may yield different results, she continued.
 

Shift Toward Unscreened Cancers

The top cancer types identified in the second round of testing were lymphoid, head and neck, bladder/urothelial, colorectal, and anal cancers. Clinicians were able to confirm clinical outcomes in 12 of 26 cases, in which cancer signals were detected. Of those 12 cases, 8 individuals received a cancer diagnosis and 4 did not have cancer. The remaining 14 of 26 cases in which cancer signals were detected are still under investigation.

“We found a shift away from USPSTF screen-detected cancers, like breast, lung, and prostate, and relative increase in unscreened urinary, head and neck, and lymphoid cancers, with 75% of cancers being those without any screening guidelines,” Dr. Gordon said in an interview.

She added that patients who choose to retest may have different cancer rates for several reasons, including bias toward a population that is health conscious and adhered to all recommended cancer screening.

“So the shift toward unscreened cancers is not unexpected and highlights the value of Galleri,” she said, but also acknowledged that “continued monitoring is needed to see if this translates in a persistent finding over time and tests.”
 

Shift Toward Early-Stage Cancers

Staging information was available for five cases, and Dr. Gordon highlighted in her talk that four of these confirmed cancers were stage I, including cancers of the anus, head and neck, bladder, and lymphoma. The fifth confirmed cancer with staging information was stage IV ovarian cancer.

“It is still early, and the numbers are very small, but the detection of early-stage cancers with second annual testing is very encouraging as these are the cases where MCED testing could have the greatest impact in improving outcomes through earlier treatment,” Dr. Gordon told this publication.

During an interview after the talk, Kenneth L. Kehl, MD, MPH, echoed that data must be confirmed in larger cohorts.

“The shift toward earlier stage cancers that are less detectable by standard screening methods is an interesting result, but we need to be cautious since the numbers were relatively small, and we do not have data on cancers that were diagnosed among patients whose second MCED test was also negative,” said Dr. Kehl, a medical oncologist at Dana-Farber Cancer Institute, Boston.
 

MCED Results Could Help Direct Diagnostic Workup

The test’s ability to predict the organ of origin was highly accurate, correctly identifying the cancer type in all eight confirmed cases. Among the eight cases with a confirmed cancer diagnosis, the accuracy of the first prediction was 100%, and diagnoses included invasive cancers across multiple tissues and organs, including anus, colon, head and neck, urothelial tract, ovary, and the lymphatic system.

“The fact that the site of origin for 100% of confirmed cancers was accurately predicted with GRAIL’s CSO by Galleri test confirms the promise that this can guide workup when a cancer signal is detected,” Dr. Gordon noted in the interview.
 

Looking Ahead

Dr. Kehl, who was not involved in the MCED study, noted in an interview that “further data on test characteristics beyond positive predictive value, including the sensitivity, specificity, and negative predictive value, as well as demonstration of clinical benefit — ideally in a randomized trial — will likely be required for MCED testing to become a standard public health recommendation.”

He added that challenges associated with implementing annual screening with MCED tests include the risks of both false positives and false negatives as testing becomes more widely available.

“False positives cause anxiety and lead to additional testing that may carry its own risks, and we need to understand if potentially false negative tests will be associated with less uptake of established screening strategies,” Dr. Kehl said in an interview. However, he noted that serial testing could lead to more frequent diagnoses of early-stage cancers that may be less detectable by standard methods.

Dr. Gordon reported financial relationships with GRAIL LLC and Genetic Technologies Corporation. Dr. Kehl reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — A novel multicancer early detection (MCED) blood test has demonstrated promising real-world results in detecting new cancers, including several cases of early-stage disease.

This was the conclusion of recent data presented by Ora Karp Gordon, MD, MS, during a session at the American Association for Cancer Research annual meeting.

The MCED test, known as Galleri, was made clinically available in the United States in April 2021. Developed by GRAIL LLC, the test analyzes cell-free DNA in the blood using targeted methylation analysis and machine learning to detect the presence of a cancer signal and determine its organ of origin or cancer signal origin. The initial screening of over 53,000 individuals with the Galleri test detected a cancer signal in 1.1% of participants.

The new real-world analysis examines the outcomes of repeat MCED testing in 5,794 individuals.

The study looked at individuals who initially received a ‘no cancer signal detected’ result and then underwent a second Galleri test. Over 80% of participants received their follow-up test 10-18 months after the first, with a median interval between blood draws of 12.9 months.

“The repeat tests detect those cancer cases that have reached the detection threshold since their last MCED test, which should be less than one year of incidence,” Dr. Gordon, professor at Saint John’s Cancer Institute, Santa Monica, California, said in an interview. “We are just now starting to see results from patients who get their second and even third round of screening.”

“Galleri is recommended to be used annually in addition to USPSTF [US Preventive Services Task Force]–recommended cancer screening tests, like mammography and colonoscopy,” she said.

This recommendation is based on a modeling study suggesting that annual screening would improve stage shift, diagnostic yield, and potentially mortality when compared to biennial screening, although biennial screening was still favorable compared with no screening, she explained.
 

Early Real-World Evidence of Repeat Testing

Among the cohort of 5,794 individuals who received repeat testing, 26 received a positive cancer signal on their second test, yielding a cancer signal detection rate of 0.45% (95% CI: 0.31%-0.66%). The cancer signal detection rate was slightly higher in men. The rate was 0.50% (95% CI: 0.32%-0.81%; 17 of 3367) in men versus 0.37% (95% CI: 0.2%-0.7%; 9 of 2427) in women.

During her presentation, Dr. Gordon highlighted that the repeat testing signal detection rate was lower than the initial 0.95% rate (95% CI: 0.87-1.0; 510 of 53,744) seen in the previous larger cohort of patients who were retested at 1 year.

She acknowledged that the lower cancer signal detection rate of repeat testing may indicate some degree of ‘early adopter’ bias, where those who return for a second test are systematically different from the general screening population. This could suggest that broader population-level screening may yield different results, she continued.
 

Shift Toward Unscreened Cancers

The top cancer types identified in the second round of testing were lymphoid, head and neck, bladder/urothelial, colorectal, and anal cancers. Clinicians were able to confirm clinical outcomes in 12 of 26 cases, in which cancer signals were detected. Of those 12 cases, 8 individuals received a cancer diagnosis and 4 did not have cancer. The remaining 14 of 26 cases in which cancer signals were detected are still under investigation.

“We found a shift away from USPSTF screen-detected cancers, like breast, lung, and prostate, and relative increase in unscreened urinary, head and neck, and lymphoid cancers, with 75% of cancers being those without any screening guidelines,” Dr. Gordon said in an interview.

She added that patients who choose to retest may have different cancer rates for several reasons, including bias toward a population that is health conscious and adhered to all recommended cancer screening.

“So the shift toward unscreened cancers is not unexpected and highlights the value of Galleri,” she said, but also acknowledged that “continued monitoring is needed to see if this translates in a persistent finding over time and tests.”
 

Shift Toward Early-Stage Cancers

Staging information was available for five cases, and Dr. Gordon highlighted in her talk that four of these confirmed cancers were stage I, including cancers of the anus, head and neck, bladder, and lymphoma. The fifth confirmed cancer with staging information was stage IV ovarian cancer.

“It is still early, and the numbers are very small, but the detection of early-stage cancers with second annual testing is very encouraging as these are the cases where MCED testing could have the greatest impact in improving outcomes through earlier treatment,” Dr. Gordon told this publication.

During an interview after the talk, Kenneth L. Kehl, MD, MPH, echoed that data must be confirmed in larger cohorts.

“The shift toward earlier stage cancers that are less detectable by standard screening methods is an interesting result, but we need to be cautious since the numbers were relatively small, and we do not have data on cancers that were diagnosed among patients whose second MCED test was also negative,” said Dr. Kehl, a medical oncologist at Dana-Farber Cancer Institute, Boston.
 

MCED Results Could Help Direct Diagnostic Workup

The test’s ability to predict the organ of origin was highly accurate, correctly identifying the cancer type in all eight confirmed cases. Among the eight cases with a confirmed cancer diagnosis, the accuracy of the first prediction was 100%, and diagnoses included invasive cancers across multiple tissues and organs, including anus, colon, head and neck, urothelial tract, ovary, and the lymphatic system.

“The fact that the site of origin for 100% of confirmed cancers was accurately predicted with GRAIL’s CSO by Galleri test confirms the promise that this can guide workup when a cancer signal is detected,” Dr. Gordon noted in the interview.
 

Looking Ahead

Dr. Kehl, who was not involved in the MCED study, noted in an interview that “further data on test characteristics beyond positive predictive value, including the sensitivity, specificity, and negative predictive value, as well as demonstration of clinical benefit — ideally in a randomized trial — will likely be required for MCED testing to become a standard public health recommendation.”

He added that challenges associated with implementing annual screening with MCED tests include the risks of both false positives and false negatives as testing becomes more widely available.

“False positives cause anxiety and lead to additional testing that may carry its own risks, and we need to understand if potentially false negative tests will be associated with less uptake of established screening strategies,” Dr. Kehl said in an interview. However, he noted that serial testing could lead to more frequent diagnoses of early-stage cancers that may be less detectable by standard methods.

Dr. Gordon reported financial relationships with GRAIL LLC and Genetic Technologies Corporation. Dr. Kehl reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — A novel multicancer early detection (MCED) blood test has demonstrated promising real-world results in detecting new cancers, including several cases of early-stage disease.

This was the conclusion of recent data presented by Ora Karp Gordon, MD, MS, during a session at the American Association for Cancer Research annual meeting.

The MCED test, known as Galleri, was made clinically available in the United States in April 2021. Developed by GRAIL LLC, the test analyzes cell-free DNA in the blood using targeted methylation analysis and machine learning to detect the presence of a cancer signal and determine its organ of origin or cancer signal origin. The initial screening of over 53,000 individuals with the Galleri test detected a cancer signal in 1.1% of participants.

The new real-world analysis examines the outcomes of repeat MCED testing in 5,794 individuals.

The study looked at individuals who initially received a ‘no cancer signal detected’ result and then underwent a second Galleri test. Over 80% of participants received their follow-up test 10-18 months after the first, with a median interval between blood draws of 12.9 months.

“The repeat tests detect those cancer cases that have reached the detection threshold since their last MCED test, which should be less than one year of incidence,” Dr. Gordon, professor at Saint John’s Cancer Institute, Santa Monica, California, said in an interview. “We are just now starting to see results from patients who get their second and even third round of screening.”

“Galleri is recommended to be used annually in addition to USPSTF [US Preventive Services Task Force]–recommended cancer screening tests, like mammography and colonoscopy,” she said.

This recommendation is based on a modeling study suggesting that annual screening would improve stage shift, diagnostic yield, and potentially mortality when compared to biennial screening, although biennial screening was still favorable compared with no screening, she explained.
 

Early Real-World Evidence of Repeat Testing

Among the cohort of 5,794 individuals who received repeat testing, 26 received a positive cancer signal on their second test, yielding a cancer signal detection rate of 0.45% (95% CI: 0.31%-0.66%). The cancer signal detection rate was slightly higher in men. The rate was 0.50% (95% CI: 0.32%-0.81%; 17 of 3367) in men versus 0.37% (95% CI: 0.2%-0.7%; 9 of 2427) in women.

During her presentation, Dr. Gordon highlighted that the repeat testing signal detection rate was lower than the initial 0.95% rate (95% CI: 0.87-1.0; 510 of 53,744) seen in the previous larger cohort of patients who were retested at 1 year.

She acknowledged that the lower cancer signal detection rate of repeat testing may indicate some degree of ‘early adopter’ bias, where those who return for a second test are systematically different from the general screening population. This could suggest that broader population-level screening may yield different results, she continued.
 

Shift Toward Unscreened Cancers

The top cancer types identified in the second round of testing were lymphoid, head and neck, bladder/urothelial, colorectal, and anal cancers. Clinicians were able to confirm clinical outcomes in 12 of 26 cases, in which cancer signals were detected. Of those 12 cases, 8 individuals received a cancer diagnosis and 4 did not have cancer. The remaining 14 of 26 cases in which cancer signals were detected are still under investigation.

“We found a shift away from USPSTF screen-detected cancers, like breast, lung, and prostate, and relative increase in unscreened urinary, head and neck, and lymphoid cancers, with 75% of cancers being those without any screening guidelines,” Dr. Gordon said in an interview.

She added that patients who choose to retest may have different cancer rates for several reasons, including bias toward a population that is health conscious and adhered to all recommended cancer screening.

“So the shift toward unscreened cancers is not unexpected and highlights the value of Galleri,” she said, but also acknowledged that “continued monitoring is needed to see if this translates in a persistent finding over time and tests.”
 

Shift Toward Early-Stage Cancers

Staging information was available for five cases, and Dr. Gordon highlighted in her talk that four of these confirmed cancers were stage I, including cancers of the anus, head and neck, bladder, and lymphoma. The fifth confirmed cancer with staging information was stage IV ovarian cancer.

“It is still early, and the numbers are very small, but the detection of early-stage cancers with second annual testing is very encouraging as these are the cases where MCED testing could have the greatest impact in improving outcomes through earlier treatment,” Dr. Gordon told this publication.

During an interview after the talk, Kenneth L. Kehl, MD, MPH, echoed that data must be confirmed in larger cohorts.

“The shift toward earlier stage cancers that are less detectable by standard screening methods is an interesting result, but we need to be cautious since the numbers were relatively small, and we do not have data on cancers that were diagnosed among patients whose second MCED test was also negative,” said Dr. Kehl, a medical oncologist at Dana-Farber Cancer Institute, Boston.
 

MCED Results Could Help Direct Diagnostic Workup

The test’s ability to predict the organ of origin was highly accurate, correctly identifying the cancer type in all eight confirmed cases. Among the eight cases with a confirmed cancer diagnosis, the accuracy of the first prediction was 100%, and diagnoses included invasive cancers across multiple tissues and organs, including anus, colon, head and neck, urothelial tract, ovary, and the lymphatic system.

“The fact that the site of origin for 100% of confirmed cancers was accurately predicted with GRAIL’s CSO by Galleri test confirms the promise that this can guide workup when a cancer signal is detected,” Dr. Gordon noted in the interview.
 

Looking Ahead

Dr. Kehl, who was not involved in the MCED study, noted in an interview that “further data on test characteristics beyond positive predictive value, including the sensitivity, specificity, and negative predictive value, as well as demonstration of clinical benefit — ideally in a randomized trial — will likely be required for MCED testing to become a standard public health recommendation.”

He added that challenges associated with implementing annual screening with MCED tests include the risks of both false positives and false negatives as testing becomes more widely available.

“False positives cause anxiety and lead to additional testing that may carry its own risks, and we need to understand if potentially false negative tests will be associated with less uptake of established screening strategies,” Dr. Kehl said in an interview. However, he noted that serial testing could lead to more frequent diagnoses of early-stage cancers that may be less detectable by standard methods.

Dr. Gordon reported financial relationships with GRAIL LLC and Genetic Technologies Corporation. Dr. Kehl reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.