Men's Health

Testosterone replacement therapy in the treatment of hypogonadism showed no benefit in slowing the progression of prediabetes or diabetes, contrary to previous evidence that suggested potential improvements in insulin sensitivity and metabolism.

“The findings of this study suggest that testosterone replacement therapy alone should not be used as a therapeutic intervention to prevent or treat diabetes in men with hypogonadism,” reported the authors of research published this month in JAMA Internal Medicine.

The suggestion that testosterone replacement could prevent or slow diabetes stems from numerous studies linking testosterone deficiency to a host of adverse effects that include increases in insulin resistance and an increased risk for prediabetes and type 2 diabetes.

Furthermore, one recent uncontrolled study showed a lower rate of progression from prediabetes to diabetes in testosterone-treated vs untreated men with hypogonadism.

But with no known randomized clinical trials evaluating the effects of testosterone on diabetes in the absence of a concurrent lifestyle intervention, Shalender Bhasin, MB, of the Research Program in Men’s Health: Aging and Metabolism, at Brigham and Women’s Hospital, Harvard Medical School, Boston, and colleagues conducted a substudy of the randomized TRAVERSE trial, which was conducted at 316 sites in the United States.

“We hypothesized that testosterone replacement therapy for men with hypogonadism and prediabetes would be associated with a significantly lower rate of progression to diabetes,” they wrote.

In the study, named the TRAVERSE Diabetes Study, 5204 participants aged between 40 and 85 years with hypogonadism as well as prediabetes (n = 1175) or diabetes (n = 3880) were randomized 1:1 to receive treatment either with 1.62% testosterone gel or placebo gel.

The participants had a mean age of 63.2 years, and the mean A1c among those with prediabetes was 5.8%.

For the primary outcome, the risk for progression to diabetes did not differ significantly between the testosterone-treated and placebo groups at 6 months (0.7% vs 1.4%), 12 months (7.8% vs 10.7%), 24 months (10.1% vs 14.6%), 36 months (12.8% vs 15.8%), or 48 months (13.4% vs 15.7%; omnibus test P = .49).

There were also no significant differences in terms of glycemic remission and the changes in glucose and A1c levels between the testosterone- and placebo-treated men with prediabetes or diabetes, consistent with findings from previous smaller trials.

The authors pointed out that the participants in the TRAVERSE trial had mild to moderate testosterone deficiency, and “it is possible that greater improvements in insulin sensitivity may be observed in men with severe testosterone deficiency.”

However, they noted that most men with hypogonadism who are treated with testosterone replacement therapy have only mild testosterone deficiency.

The parent TRAVERSE study did show testosterone replacement therapy to be associated with higher incidences of venous thromboembolism, atrial fibrillation, and acute kidney injury; however, no additional between-group differences were observed based on diabetes or prediabetes status.

“The findings of this study do not support the use of testosterone replacement therapy alone to prevent or to treat diabetes in men with hypogonadism,” the authors concluded.
 

Study ‘Overcomes Limitations of Prior Studies’

In an editorial published concurrently with the study, Lona Mody, MD, of the Division of Geriatric and Palliative Care Medicine, University of Michigan Medical School, in Ann Arbor, and colleagues underscored that “the results of this study suggest that testosterone replacement therapy will not benefit glycemic control in men without hypogonadism despite the inappropriately high rates of use in this group.”

Further commenting, Dr. Mody elaborated on the high rates of use, noting that data have shown androgen use among men over 40 years increased more than threefold from 0.81% in 2001 to 2.91% in 2011.

“Based on sales data, testosterone prescribing has increased 100-fold from $18 million in the late 1980s to $1.8 billion over three decades,” Dr. Mody said.

She noted that while some previous research has shown a similar lack of benefits, “the current study overcomes some limitations of prior studies.”

Ultimately, the evidence indicated that “the only major indication for testosterone replacement therapy remains to treat bothersome symptoms of hypogonadism,” Dr. Mody said. “It does not appear to have metabolic benefits.”

This trial was funded by a consortium of testosterone manufacturers led by AbbVie Inc., with additional financial support provided by Endo Pharmaceuticals, Acerus Pharmaceuticals Corporation, and Upsher-Smith Laboratories, LLC.
 

A version of this article appeared on Medscape.com.

Testosterone replacement therapy in the treatment of hypogonadism showed no benefit in slowing the progression of prediabetes or diabetes, contrary to previous evidence that suggested potential improvements in insulin sensitivity and metabolism.

“The findings of this study suggest that testosterone replacement therapy alone should not be used as a therapeutic intervention to prevent or treat diabetes in men with hypogonadism,” reported the authors of research published this month in JAMA Internal Medicine.

The suggestion that testosterone replacement could prevent or slow diabetes stems from numerous studies linking testosterone deficiency to a host of adverse effects that include increases in insulin resistance and an increased risk for prediabetes and type 2 diabetes.

Furthermore, one recent uncontrolled study showed a lower rate of progression from prediabetes to diabetes in testosterone-treated vs untreated men with hypogonadism.

But with no known randomized clinical trials evaluating the effects of testosterone on diabetes in the absence of a concurrent lifestyle intervention, Shalender Bhasin, MB, of the Research Program in Men’s Health: Aging and Metabolism, at Brigham and Women’s Hospital, Harvard Medical School, Boston, and colleagues conducted a substudy of the randomized TRAVERSE trial, which was conducted at 316 sites in the United States.

“We hypothesized that testosterone replacement therapy for men with hypogonadism and prediabetes would be associated with a significantly lower rate of progression to diabetes,” they wrote.

In the study, named the TRAVERSE Diabetes Study, 5204 participants aged between 40 and 85 years with hypogonadism as well as prediabetes (n = 1175) or diabetes (n = 3880) were randomized 1:1 to receive treatment either with 1.62% testosterone gel or placebo gel.

The participants had a mean age of 63.2 years, and the mean A1c among those with prediabetes was 5.8%.

For the primary outcome, the risk for progression to diabetes did not differ significantly between the testosterone-treated and placebo groups at 6 months (0.7% vs 1.4%), 12 months (7.8% vs 10.7%), 24 months (10.1% vs 14.6%), 36 months (12.8% vs 15.8%), or 48 months (13.4% vs 15.7%; omnibus test P = .49).

There were also no significant differences in terms of glycemic remission and the changes in glucose and A1c levels between the testosterone- and placebo-treated men with prediabetes or diabetes, consistent with findings from previous smaller trials.

The authors pointed out that the participants in the TRAVERSE trial had mild to moderate testosterone deficiency, and “it is possible that greater improvements in insulin sensitivity may be observed in men with severe testosterone deficiency.”

However, they noted that most men with hypogonadism who are treated with testosterone replacement therapy have only mild testosterone deficiency.

The parent TRAVERSE study did show testosterone replacement therapy to be associated with higher incidences of venous thromboembolism, atrial fibrillation, and acute kidney injury; however, no additional between-group differences were observed based on diabetes or prediabetes status.

“The findings of this study do not support the use of testosterone replacement therapy alone to prevent or to treat diabetes in men with hypogonadism,” the authors concluded.
 

Study ‘Overcomes Limitations of Prior Studies’

In an editorial published concurrently with the study, Lona Mody, MD, of the Division of Geriatric and Palliative Care Medicine, University of Michigan Medical School, in Ann Arbor, and colleagues underscored that “the results of this study suggest that testosterone replacement therapy will not benefit glycemic control in men without hypogonadism despite the inappropriately high rates of use in this group.”

Further commenting, Dr. Mody elaborated on the high rates of use, noting that data have shown androgen use among men over 40 years increased more than threefold from 0.81% in 2001 to 2.91% in 2011.

“Based on sales data, testosterone prescribing has increased 100-fold from $18 million in the late 1980s to $1.8 billion over three decades,” Dr. Mody said.

She noted that while some previous research has shown a similar lack of benefits, “the current study overcomes some limitations of prior studies.”

Ultimately, the evidence indicated that “the only major indication for testosterone replacement therapy remains to treat bothersome symptoms of hypogonadism,” Dr. Mody said. “It does not appear to have metabolic benefits.”

This trial was funded by a consortium of testosterone manufacturers led by AbbVie Inc., with additional financial support provided by Endo Pharmaceuticals, Acerus Pharmaceuticals Corporation, and Upsher-Smith Laboratories, LLC.
 

A version of this article appeared on Medscape.com.

Testosterone replacement therapy in the treatment of hypogonadism showed no benefit in slowing the progression of prediabetes or diabetes, contrary to previous evidence that suggested potential improvements in insulin sensitivity and metabolism.

“The findings of this study suggest that testosterone replacement therapy alone should not be used as a therapeutic intervention to prevent or treat diabetes in men with hypogonadism,” reported the authors of research published this month in JAMA Internal Medicine.

The suggestion that testosterone replacement could prevent or slow diabetes stems from numerous studies linking testosterone deficiency to a host of adverse effects that include increases in insulin resistance and an increased risk for prediabetes and type 2 diabetes.

Furthermore, one recent uncontrolled study showed a lower rate of progression from prediabetes to diabetes in testosterone-treated vs untreated men with hypogonadism.

But with no known randomized clinical trials evaluating the effects of testosterone on diabetes in the absence of a concurrent lifestyle intervention, Shalender Bhasin, MB, of the Research Program in Men’s Health: Aging and Metabolism, at Brigham and Women’s Hospital, Harvard Medical School, Boston, and colleagues conducted a substudy of the randomized TRAVERSE trial, which was conducted at 316 sites in the United States.

“We hypothesized that testosterone replacement therapy for men with hypogonadism and prediabetes would be associated with a significantly lower rate of progression to diabetes,” they wrote.

In the study, named the TRAVERSE Diabetes Study, 5204 participants aged between 40 and 85 years with hypogonadism as well as prediabetes (n = 1175) or diabetes (n = 3880) were randomized 1:1 to receive treatment either with 1.62% testosterone gel or placebo gel.

The participants had a mean age of 63.2 years, and the mean A1c among those with prediabetes was 5.8%.

For the primary outcome, the risk for progression to diabetes did not differ significantly between the testosterone-treated and placebo groups at 6 months (0.7% vs 1.4%), 12 months (7.8% vs 10.7%), 24 months (10.1% vs 14.6%), 36 months (12.8% vs 15.8%), or 48 months (13.4% vs 15.7%; omnibus test P = .49).

There were also no significant differences in terms of glycemic remission and the changes in glucose and A1c levels between the testosterone- and placebo-treated men with prediabetes or diabetes, consistent with findings from previous smaller trials.

The authors pointed out that the participants in the TRAVERSE trial had mild to moderate testosterone deficiency, and “it is possible that greater improvements in insulin sensitivity may be observed in men with severe testosterone deficiency.”

However, they noted that most men with hypogonadism who are treated with testosterone replacement therapy have only mild testosterone deficiency.

The parent TRAVERSE study did show testosterone replacement therapy to be associated with higher incidences of venous thromboembolism, atrial fibrillation, and acute kidney injury; however, no additional between-group differences were observed based on diabetes or prediabetes status.

“The findings of this study do not support the use of testosterone replacement therapy alone to prevent or to treat diabetes in men with hypogonadism,” the authors concluded.
 

Study ‘Overcomes Limitations of Prior Studies’

In an editorial published concurrently with the study, Lona Mody, MD, of the Division of Geriatric and Palliative Care Medicine, University of Michigan Medical School, in Ann Arbor, and colleagues underscored that “the results of this study suggest that testosterone replacement therapy will not benefit glycemic control in men without hypogonadism despite the inappropriately high rates of use in this group.”

Further commenting, Dr. Mody elaborated on the high rates of use, noting that data have shown androgen use among men over 40 years increased more than threefold from 0.81% in 2001 to 2.91% in 2011.

“Based on sales data, testosterone prescribing has increased 100-fold from $18 million in the late 1980s to $1.8 billion over three decades,” Dr. Mody said.

She noted that while some previous research has shown a similar lack of benefits, “the current study overcomes some limitations of prior studies.”

Ultimately, the evidence indicated that “the only major indication for testosterone replacement therapy remains to treat bothersome symptoms of hypogonadism,” Dr. Mody said. “It does not appear to have metabolic benefits.”

This trial was funded by a consortium of testosterone manufacturers led by AbbVie Inc., with additional financial support provided by Endo Pharmaceuticals, Acerus Pharmaceuticals Corporation, and Upsher-Smith Laboratories, LLC.
 

A version of this article appeared on Medscape.com.

Men with cardiorespiratory fitness (CRF) who increased their CRF by more than 3% had a significantly lower risk of prostate cancer incidence, a large Swedish study found.

The prospective analysis, published in the British Journal of Sports Medicine, done in a cohort of nearly 58,000, was conducted by Kate A. Bolam, PhD, a clinical exercise physiologist at the Swedish School of Sport and Health Sciences in Stockholm.

“The findings suggest that physicians could work toward supporting patients to understand what types of activities could improve their fitness and ways they can incorporate these activities into their lives in an enjoyable way, or at the very least refer patients on to an exercise specialist,” Dr. Bolam said in an interview.

Grouped by baseline CRF, the association between change in absolute CRF and prostate cancer incidence was significant only for participants with a moderate baseline CRF. Moreover, changes in both absolute and relative CRF were not associated with prostate cancer mortality.

The lack of mortality significance may be due to the relatively few deaths from prostate cancer in the cohort, Dr. Bolam said. “It may be we weren’t powered to detect anything with such low numbers. And it’s not likely men will die from prostate cancer but more likely from more common chronic diseases such as heart disease.” The authors noted that unlike the case with other common cancers, there are relatively few preventable risk factors with strong evidence for reducing overall prostate cancer risk. “Aside from developmental factors, being diagnosed with overweight or obesity are the main risk factors for developing advanced prostate cancer, but insufficient evidence exists to extend this conclusion to non-advanced prostate cancer,” they wrote.

There is evidence, however, that exercise reduces all-cause mortality risk across many cancer types, including prostate.
 

Study details

The cohort was drawn from Swedish national health-profile database figures from 1982 to 2019. Participants completed an occupational health profile assessment including at least two valid CRF tests on a cycle ergometer. During a mean follow-up of 6.7 years, 592 (1%) of 57,652 men (mean age 41.3 years, standard deviation 10.55) were diagnosed with prostate cancer, and in 46 (.08%) prostate cancer was the primary cause of death.

An increase in absolute CRF (as a percentage of liters per minute of cardiac output) was associated with a reduced incidence risk, with a hazard ratio of 0.98 (95% CI, 0.96-0.99). Grouping participants as having increased (+3%), stable (±3%), or decreased (−3%) CRF, the investigators found increased fitness was associated with an HR for prostate cancer incidence of 0.65 (95% CI, 0.49-0.86), vs decreased fitness.

According to the authors, this and similar investigations of mechanisms behind physical activity benefits will lead to more targeted prevention recommendations. The results highlight the importance of encouraging the general public to increase CRF or reach moderate fitness levels, Dr. Bolam’s group wrote. The group is planning a similar study in breast cancer.

This study was funded by the Swedish Cancer Society. The authors declared no competing interests.

Men with cardiorespiratory fitness (CRF) who increased their CRF by more than 3% had a significantly lower risk of prostate cancer incidence, a large Swedish study found.

The prospective analysis, published in the British Journal of Sports Medicine, done in a cohort of nearly 58,000, was conducted by Kate A. Bolam, PhD, a clinical exercise physiologist at the Swedish School of Sport and Health Sciences in Stockholm.

“The findings suggest that physicians could work toward supporting patients to understand what types of activities could improve their fitness and ways they can incorporate these activities into their lives in an enjoyable way, or at the very least refer patients on to an exercise specialist,” Dr. Bolam said in an interview.

Grouped by baseline CRF, the association between change in absolute CRF and prostate cancer incidence was significant only for participants with a moderate baseline CRF. Moreover, changes in both absolute and relative CRF were not associated with prostate cancer mortality.

The lack of mortality significance may be due to the relatively few deaths from prostate cancer in the cohort, Dr. Bolam said. “It may be we weren’t powered to detect anything with such low numbers. And it’s not likely men will die from prostate cancer but more likely from more common chronic diseases such as heart disease.” The authors noted that unlike the case with other common cancers, there are relatively few preventable risk factors with strong evidence for reducing overall prostate cancer risk. “Aside from developmental factors, being diagnosed with overweight or obesity are the main risk factors for developing advanced prostate cancer, but insufficient evidence exists to extend this conclusion to non-advanced prostate cancer,” they wrote.

There is evidence, however, that exercise reduces all-cause mortality risk across many cancer types, including prostate.
 

Study details

The cohort was drawn from Swedish national health-profile database figures from 1982 to 2019. Participants completed an occupational health profile assessment including at least two valid CRF tests on a cycle ergometer. During a mean follow-up of 6.7 years, 592 (1%) of 57,652 men (mean age 41.3 years, standard deviation 10.55) were diagnosed with prostate cancer, and in 46 (.08%) prostate cancer was the primary cause of death.

An increase in absolute CRF (as a percentage of liters per minute of cardiac output) was associated with a reduced incidence risk, with a hazard ratio of 0.98 (95% CI, 0.96-0.99). Grouping participants as having increased (+3%), stable (±3%), or decreased (−3%) CRF, the investigators found increased fitness was associated with an HR for prostate cancer incidence of 0.65 (95% CI, 0.49-0.86), vs decreased fitness.

According to the authors, this and similar investigations of mechanisms behind physical activity benefits will lead to more targeted prevention recommendations. The results highlight the importance of encouraging the general public to increase CRF or reach moderate fitness levels, Dr. Bolam’s group wrote. The group is planning a similar study in breast cancer.

This study was funded by the Swedish Cancer Society. The authors declared no competing interests.

Men with cardiorespiratory fitness (CRF) who increased their CRF by more than 3% had a significantly lower risk of prostate cancer incidence, a large Swedish study found.

The prospective analysis, published in the British Journal of Sports Medicine, done in a cohort of nearly 58,000, was conducted by Kate A. Bolam, PhD, a clinical exercise physiologist at the Swedish School of Sport and Health Sciences in Stockholm.

“The findings suggest that physicians could work toward supporting patients to understand what types of activities could improve their fitness and ways they can incorporate these activities into their lives in an enjoyable way, or at the very least refer patients on to an exercise specialist,” Dr. Bolam said in an interview.

Grouped by baseline CRF, the association between change in absolute CRF and prostate cancer incidence was significant only for participants with a moderate baseline CRF. Moreover, changes in both absolute and relative CRF were not associated with prostate cancer mortality.

The lack of mortality significance may be due to the relatively few deaths from prostate cancer in the cohort, Dr. Bolam said. “It may be we weren’t powered to detect anything with such low numbers. And it’s not likely men will die from prostate cancer but more likely from more common chronic diseases such as heart disease.” The authors noted that unlike the case with other common cancers, there are relatively few preventable risk factors with strong evidence for reducing overall prostate cancer risk. “Aside from developmental factors, being diagnosed with overweight or obesity are the main risk factors for developing advanced prostate cancer, but insufficient evidence exists to extend this conclusion to non-advanced prostate cancer,” they wrote.

There is evidence, however, that exercise reduces all-cause mortality risk across many cancer types, including prostate.
 

Study details

The cohort was drawn from Swedish national health-profile database figures from 1982 to 2019. Participants completed an occupational health profile assessment including at least two valid CRF tests on a cycle ergometer. During a mean follow-up of 6.7 years, 592 (1%) of 57,652 men (mean age 41.3 years, standard deviation 10.55) were diagnosed with prostate cancer, and in 46 (.08%) prostate cancer was the primary cause of death.

An increase in absolute CRF (as a percentage of liters per minute of cardiac output) was associated with a reduced incidence risk, with a hazard ratio of 0.98 (95% CI, 0.96-0.99). Grouping participants as having increased (+3%), stable (±3%), or decreased (−3%) CRF, the investigators found increased fitness was associated with an HR for prostate cancer incidence of 0.65 (95% CI, 0.49-0.86), vs decreased fitness.

According to the authors, this and similar investigations of mechanisms behind physical activity benefits will lead to more targeted prevention recommendations. The results highlight the importance of encouraging the general public to increase CRF or reach moderate fitness levels, Dr. Bolam’s group wrote. The group is planning a similar study in breast cancer.

This study was funded by the Swedish Cancer Society. The authors declared no competing interests.

Men with advanced prostate cancer undergoing local therapies such as radiation therapy or radical prostatectomy experience significantly more gastrointestinal and sexual issues, along with problems with incontinence, in the following years, than systemically treated patients. These were the findings of a retrospective cohort study in JAMA Network Open.

The standard treatment of advanced prostate cancer is androgen deprivation therapy (ADT). “The role of local therapy has been debated for several years. Studies have shown that radiation therapy or radical prostatectomy can improve patient survival under certain conditions,” said Hubert Kübler, MD, director of the Clinic and Polyclinic for Urology and Pediatric Urology at the University Hospital Würzburg in Germany. “At academic centers, a local therapy is pursued for oligometastatic patients if they are fit enough.”

The hope is to spare patients the side effects of ADT over an extended period and thus improve their quality of life. “But what impact does local therapy itself have on the men’s quality of life, especially considering that the survival advantage gained may be relatively small?” wrote study author Saira Khan, PhD, MPH, assistant professor of surgery at Washington University School of Medicine in St. Louis, Missouri, and her colleagues.

Examining Side Effects

This question has not been thoroughly examined yet. “To our knowledge, this is one of the first studies investigating the side effects of local therapy in men with advanced prostate cancer for up to 5 years after treatment,” wrote the authors.

The cohort study included 5500 US veterans who were diagnosed with advanced prostate cancer between January 1999 and December 2013. The tumors were in stage T4 (tumor is fixed or has spread to adjacent structures), with regional lymph node metastases (N1), and partially detectable distant metastases (M1).

The average age was 68.7 years, and 31% received local therapy (eg, radiation therapy, radical prostatectomy, or both), and 69% received systemic therapy (eg, hormone therapy, chemotherapy, or both).

Types of Local Therapy

Combining radiation therapy and radical prostatectomy “diminishes the meaningfulness of the study results,” according to Dr. Kübler. “The issue should have been analyzed in much finer detail. Studies clearly show, for example, that radiation therapy consistently performs slightly worse than prostatectomy in terms of gastrointestinal complaints.”

In their paper, the researchers reported that the prevalence of side effects was high, regardless of the therapy. Overall, 916 men (75.2%) with initial local therapy and 897 men (67.1%) with initial systemic therapy reported experiencing at least one side effect lasting more than 2 years and up to 5 years.

In the first year after the initial therapy, men who underwent local therapy, compared with those who underwent systemic therapy, experienced more of the following symptoms:

• Gastrointestinal issues (odds ratio [OR], 4.08)
• Pain (OR, 1.57)
• Sexual dysfunction (OR, 2.96)
• Urinary problems, predominantly incontinence (OR, 2.25)

Lasting Side Effects

Even up to year 5 after the initial therapy, men with local therapy reported more gastrointestinal and sexual issues, as well as more frequent incontinence, than those with systemic therapy. Only the frequency of pain equalized between the two groups in the second year.

“Our results are consistent with the known side effect profile [of local therapy] in patients with clinically localized prostate cancer receiving surgery or radiation therapy instead of active surveillance,” wrote the authors.

The comparison in advanced prostate cancer, however, is not with active surveillance but with ADT. “As the study confirmed, ADT is associated with various side effects,” said Dr. Kübler. Nevertheless, it was associated with fewer side effects than local therapy in this study. The concept behind local therapy (improving prognosis while avoiding local problems) is challenging to reconcile with these results.

Contradictory Data

The results also contradict findings from other studies. Dr. Kübler pointed to the recently presented PEACE-1 study, where “local complications and issues were reduced through local therapy in high-volume and high-risk patients.”

The study did not consider subsequent interventions, such as how many patients needed transurethral manipulation in the later course of the disease to address local problems. “There are older data showing that a radical prostatectomy can reduce the need for further resections,” Dr. Kübler added.

“I find it difficult to reconcile these data with other data and with my personal experience,” said Dr. Kübler. However, he agreed with the study authors’ conclusion, emphasizing the importance of informing patients about expected side effects of local therapy in the context of potentially marginal improvements in survival.

Different Situation in Germany

“As practitioners, we sometimes underestimate the side effects we subject our patients to. We need to talk to our patients about the prognosis improvement that comes with side effects,” said Dr. Kübler. He added that a similar study in Germany might yield different results. “Dr. Khan and her colleagues examined a very specific patient population: Namely, veterans. This patient clientele often faces many social difficulties, and the treatment structure in US veterans’ care differs significantly from ours.”

This article was translated from the Medscape German edition. A version of this article appeared on Medscape.com.

Men with advanced prostate cancer undergoing local therapies such as radiation therapy or radical prostatectomy experience significantly more gastrointestinal and sexual issues, along with problems with incontinence, in the following years, than systemically treated patients. These were the findings of a retrospective cohort study in JAMA Network Open.

The standard treatment of advanced prostate cancer is androgen deprivation therapy (ADT). “The role of local therapy has been debated for several years. Studies have shown that radiation therapy or radical prostatectomy can improve patient survival under certain conditions,” said Hubert Kübler, MD, director of the Clinic and Polyclinic for Urology and Pediatric Urology at the University Hospital Würzburg in Germany. “At academic centers, a local therapy is pursued for oligometastatic patients if they are fit enough.”

The hope is to spare patients the side effects of ADT over an extended period and thus improve their quality of life. “But what impact does local therapy itself have on the men’s quality of life, especially considering that the survival advantage gained may be relatively small?” wrote study author Saira Khan, PhD, MPH, assistant professor of surgery at Washington University School of Medicine in St. Louis, Missouri, and her colleagues.

Examining Side Effects

This question has not been thoroughly examined yet. “To our knowledge, this is one of the first studies investigating the side effects of local therapy in men with advanced prostate cancer for up to 5 years after treatment,” wrote the authors.

The cohort study included 5500 US veterans who were diagnosed with advanced prostate cancer between January 1999 and December 2013. The tumors were in stage T4 (tumor is fixed or has spread to adjacent structures), with regional lymph node metastases (N1), and partially detectable distant metastases (M1).

The average age was 68.7 years, and 31% received local therapy (eg, radiation therapy, radical prostatectomy, or both), and 69% received systemic therapy (eg, hormone therapy, chemotherapy, or both).

Types of Local Therapy

Combining radiation therapy and radical prostatectomy “diminishes the meaningfulness of the study results,” according to Dr. Kübler. “The issue should have been analyzed in much finer detail. Studies clearly show, for example, that radiation therapy consistently performs slightly worse than prostatectomy in terms of gastrointestinal complaints.”

In their paper, the researchers reported that the prevalence of side effects was high, regardless of the therapy. Overall, 916 men (75.2%) with initial local therapy and 897 men (67.1%) with initial systemic therapy reported experiencing at least one side effect lasting more than 2 years and up to 5 years.

In the first year after the initial therapy, men who underwent local therapy, compared with those who underwent systemic therapy, experienced more of the following symptoms:

• Gastrointestinal issues (odds ratio [OR], 4.08)
• Pain (OR, 1.57)
• Sexual dysfunction (OR, 2.96)
• Urinary problems, predominantly incontinence (OR, 2.25)

Lasting Side Effects

Even up to year 5 after the initial therapy, men with local therapy reported more gastrointestinal and sexual issues, as well as more frequent incontinence, than those with systemic therapy. Only the frequency of pain equalized between the two groups in the second year.

“Our results are consistent with the known side effect profile [of local therapy] in patients with clinically localized prostate cancer receiving surgery or radiation therapy instead of active surveillance,” wrote the authors.

The comparison in advanced prostate cancer, however, is not with active surveillance but with ADT. “As the study confirmed, ADT is associated with various side effects,” said Dr. Kübler. Nevertheless, it was associated with fewer side effects than local therapy in this study. The concept behind local therapy (improving prognosis while avoiding local problems) is challenging to reconcile with these results.

Contradictory Data

The results also contradict findings from other studies. Dr. Kübler pointed to the recently presented PEACE-1 study, where “local complications and issues were reduced through local therapy in high-volume and high-risk patients.”

The study did not consider subsequent interventions, such as how many patients needed transurethral manipulation in the later course of the disease to address local problems. “There are older data showing that a radical prostatectomy can reduce the need for further resections,” Dr. Kübler added.

“I find it difficult to reconcile these data with other data and with my personal experience,” said Dr. Kübler. However, he agreed with the study authors’ conclusion, emphasizing the importance of informing patients about expected side effects of local therapy in the context of potentially marginal improvements in survival.

Different Situation in Germany

“As practitioners, we sometimes underestimate the side effects we subject our patients to. We need to talk to our patients about the prognosis improvement that comes with side effects,” said Dr. Kübler. He added that a similar study in Germany might yield different results. “Dr. Khan and her colleagues examined a very specific patient population: Namely, veterans. This patient clientele often faces many social difficulties, and the treatment structure in US veterans’ care differs significantly from ours.”

This article was translated from the Medscape German edition. A version of this article appeared on Medscape.com.

Men with advanced prostate cancer undergoing local therapies such as radiation therapy or radical prostatectomy experience significantly more gastrointestinal and sexual issues, along with problems with incontinence, in the following years, than systemically treated patients. These were the findings of a retrospective cohort study in JAMA Network Open.

The standard treatment of advanced prostate cancer is androgen deprivation therapy (ADT). “The role of local therapy has been debated for several years. Studies have shown that radiation therapy or radical prostatectomy can improve patient survival under certain conditions,” said Hubert Kübler, MD, director of the Clinic and Polyclinic for Urology and Pediatric Urology at the University Hospital Würzburg in Germany. “At academic centers, a local therapy is pursued for oligometastatic patients if they are fit enough.”

The hope is to spare patients the side effects of ADT over an extended period and thus improve their quality of life. “But what impact does local therapy itself have on the men’s quality of life, especially considering that the survival advantage gained may be relatively small?” wrote study author Saira Khan, PhD, MPH, assistant professor of surgery at Washington University School of Medicine in St. Louis, Missouri, and her colleagues.

Examining Side Effects

This question has not been thoroughly examined yet. “To our knowledge, this is one of the first studies investigating the side effects of local therapy in men with advanced prostate cancer for up to 5 years after treatment,” wrote the authors.

The cohort study included 5500 US veterans who were diagnosed with advanced prostate cancer between January 1999 and December 2013. The tumors were in stage T4 (tumor is fixed or has spread to adjacent structures), with regional lymph node metastases (N1), and partially detectable distant metastases (M1).

The average age was 68.7 years, and 31% received local therapy (eg, radiation therapy, radical prostatectomy, or both), and 69% received systemic therapy (eg, hormone therapy, chemotherapy, or both).

Types of Local Therapy

Combining radiation therapy and radical prostatectomy “diminishes the meaningfulness of the study results,” according to Dr. Kübler. “The issue should have been analyzed in much finer detail. Studies clearly show, for example, that radiation therapy consistently performs slightly worse than prostatectomy in terms of gastrointestinal complaints.”

In their paper, the researchers reported that the prevalence of side effects was high, regardless of the therapy. Overall, 916 men (75.2%) with initial local therapy and 897 men (67.1%) with initial systemic therapy reported experiencing at least one side effect lasting more than 2 years and up to 5 years.

In the first year after the initial therapy, men who underwent local therapy, compared with those who underwent systemic therapy, experienced more of the following symptoms:

• Gastrointestinal issues (odds ratio [OR], 4.08)
• Pain (OR, 1.57)
• Sexual dysfunction (OR, 2.96)
• Urinary problems, predominantly incontinence (OR, 2.25)

Lasting Side Effects

Even up to year 5 after the initial therapy, men with local therapy reported more gastrointestinal and sexual issues, as well as more frequent incontinence, than those with systemic therapy. Only the frequency of pain equalized between the two groups in the second year.

“Our results are consistent with the known side effect profile [of local therapy] in patients with clinically localized prostate cancer receiving surgery or radiation therapy instead of active surveillance,” wrote the authors.

The comparison in advanced prostate cancer, however, is not with active surveillance but with ADT. “As the study confirmed, ADT is associated with various side effects,” said Dr. Kübler. Nevertheless, it was associated with fewer side effects than local therapy in this study. The concept behind local therapy (improving prognosis while avoiding local problems) is challenging to reconcile with these results.

Contradictory Data

The results also contradict findings from other studies. Dr. Kübler pointed to the recently presented PEACE-1 study, where “local complications and issues were reduced through local therapy in high-volume and high-risk patients.”

The study did not consider subsequent interventions, such as how many patients needed transurethral manipulation in the later course of the disease to address local problems. “There are older data showing that a radical prostatectomy can reduce the need for further resections,” Dr. Kübler added.

“I find it difficult to reconcile these data with other data and with my personal experience,” said Dr. Kübler. However, he agreed with the study authors’ conclusion, emphasizing the importance of informing patients about expected side effects of local therapy in the context of potentially marginal improvements in survival.

Different Situation in Germany

“As practitioners, we sometimes underestimate the side effects we subject our patients to. We need to talk to our patients about the prognosis improvement that comes with side effects,” said Dr. Kübler. He added that a similar study in Germany might yield different results. “Dr. Khan and her colleagues examined a very specific patient population: Namely, veterans. This patient clientele often faces many social difficulties, and the treatment structure in US veterans’ care differs significantly from ours.”

This article was translated from the Medscape German edition. A version of this article appeared on Medscape.com.

Lowering the recommended age for baseline prostate-specific antigen (PSA) would reduce prostate cancer deaths by about 30% in Black men without significantly increasing the rate of overdiagnosis, according to new screening guidelines from the Prostate Cancer Foundation.

Specifically, baseline PSA testing in Black men should begin at age 40-45, sooner than current guidelines recommend, and should be followed by regular screening intervals, preferably annually, at least until age 70, a multidisciplinary panel of experts and patient advocates determined based on a comprehensive literature review.

The panel’s findings were presented in a poster at the ASCO Genitourinary Symposium.

“Black men in the United States are considered a high-risk population for being diagnosed with and dying from prostate cancer,” lead author Isla Garraway, MD, PhD, of the University of California, Los Angeles, and colleagues wrote. Specifically, Black men are about two times more likely to be diagnosed with and die from prostate cancer than White men. But, the authors continued, “few guidelines have outlined specific recommendations for PSA-based prostate cancer screening among Black men.”

The US Preventive Services Taskforce recommendations, which are currently being updated, set the PSA screening start age at 55. The task force recommendations, which dictate insurance coverage in the United States, acknowledged “a potential mortality benefit for African American men when beginning screening before age 55 years” but did not explicitly recommend screening earlier.

Current guidelines from the American Cancer Society call for discussions about screening in average-risk men to begin at age 50-55. The recommendations do specify lowering the age to 45 for those at a high risk for prostate cancer, which includes Black men as well as those with a first-degree relative diagnosed with prostate cancer before age 65. In some cases, screening can begin at age 40 in the highest risk men — those with more than one first-degree relative who had prostate cancer at a young age.

The Prostate Cancer Foundation “wanted to address the confusion around different guideline statements and the lack of clarity around screening recommendations for Black men,” said William K. Oh, MD, of The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York City, who chaired the panel for the new guidelines. “We thus convened a distinguished panel of experts from diverse backgrounds and expertise to create six guidelines statements to help Black men, their families, and their healthcare providers to consider options for prostate cancer screening based on the best available evidence.”

After reviewing 287, the expert panel developed six new guideline statements, reaching at least 80% consensus among panel members, addressing screening for Black men:

Because Black men are at a high risk for prostate cancer, the benefits of screening generally outweigh the risks.

PSA testing should be considered first line for prostate cancer screening, although some providers may recommend an optional digital rectal exam in addition to the PSA test.

Black men should engage in shared decision-making with their healthcare providers and other trusted sources of information to learn about the pros and cons of screening.

For Black men who elect screening, a baseline PSA test should be done between ages 40 and 45, and annual PSA screening should be strongly considered based on the PSA value and the individual’s health status.

Black men over age 70 who have been undergoing prostate cancer screening should talk with their healthcare provider about whether to continue PSA testing and make an informed decision based on their age, life expectancy, health status, family history, and prior PSA levels.

Black men who are at even higher risk due to a strong family history and/or known carriers of high-risk genetic variants should consider initiating annual PSA screening as early as age 40.

These statements are based on “the best available evidence, which overwhelmingly supports the conclusion that Black men in the US could benefit from a risk-adapted PSA screening,” the investigators concluded, noting that the latest evidence “warrants revisiting current recommendations for early [prostate cancer] detection in Black men from other national guideline groups.”

“We believe that the outcome of these more directed guidelines will be to give clarity to these men,” Dr. Oh added.

This research was funded by the Prostate Cancer Foundation, National Cancer Institute, Veterans Affairs, Jean Perkins Foundation, and Department of Defense. Dr. Garraway reported having no disclosures.

A version of this article appeared on Medscape.com.

Lowering the recommended age for baseline prostate-specific antigen (PSA) would reduce prostate cancer deaths by about 30% in Black men without significantly increasing the rate of overdiagnosis, according to new screening guidelines from the Prostate Cancer Foundation.

Specifically, baseline PSA testing in Black men should begin at age 40-45, sooner than current guidelines recommend, and should be followed by regular screening intervals, preferably annually, at least until age 70, a multidisciplinary panel of experts and patient advocates determined based on a comprehensive literature review.

The panel’s findings were presented in a poster at the ASCO Genitourinary Symposium.

“Black men in the United States are considered a high-risk population for being diagnosed with and dying from prostate cancer,” lead author Isla Garraway, MD, PhD, of the University of California, Los Angeles, and colleagues wrote. Specifically, Black men are about two times more likely to be diagnosed with and die from prostate cancer than White men. But, the authors continued, “few guidelines have outlined specific recommendations for PSA-based prostate cancer screening among Black men.”

The US Preventive Services Taskforce recommendations, which are currently being updated, set the PSA screening start age at 55. The task force recommendations, which dictate insurance coverage in the United States, acknowledged “a potential mortality benefit for African American men when beginning screening before age 55 years” but did not explicitly recommend screening earlier.

Current guidelines from the American Cancer Society call for discussions about screening in average-risk men to begin at age 50-55. The recommendations do specify lowering the age to 45 for those at a high risk for prostate cancer, which includes Black men as well as those with a first-degree relative diagnosed with prostate cancer before age 65. In some cases, screening can begin at age 40 in the highest risk men — those with more than one first-degree relative who had prostate cancer at a young age.

The Prostate Cancer Foundation “wanted to address the confusion around different guideline statements and the lack of clarity around screening recommendations for Black men,” said William K. Oh, MD, of The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York City, who chaired the panel for the new guidelines. “We thus convened a distinguished panel of experts from diverse backgrounds and expertise to create six guidelines statements to help Black men, their families, and their healthcare providers to consider options for prostate cancer screening based on the best available evidence.”

After reviewing 287, the expert panel developed six new guideline statements, reaching at least 80% consensus among panel members, addressing screening for Black men:

Because Black men are at a high risk for prostate cancer, the benefits of screening generally outweigh the risks.

PSA testing should be considered first line for prostate cancer screening, although some providers may recommend an optional digital rectal exam in addition to the PSA test.

Black men should engage in shared decision-making with their healthcare providers and other trusted sources of information to learn about the pros and cons of screening.

For Black men who elect screening, a baseline PSA test should be done between ages 40 and 45, and annual PSA screening should be strongly considered based on the PSA value and the individual’s health status.

Black men over age 70 who have been undergoing prostate cancer screening should talk with their healthcare provider about whether to continue PSA testing and make an informed decision based on their age, life expectancy, health status, family history, and prior PSA levels.

Black men who are at even higher risk due to a strong family history and/or known carriers of high-risk genetic variants should consider initiating annual PSA screening as early as age 40.

These statements are based on “the best available evidence, which overwhelmingly supports the conclusion that Black men in the US could benefit from a risk-adapted PSA screening,” the investigators concluded, noting that the latest evidence “warrants revisiting current recommendations for early [prostate cancer] detection in Black men from other national guideline groups.”

“We believe that the outcome of these more directed guidelines will be to give clarity to these men,” Dr. Oh added.

This research was funded by the Prostate Cancer Foundation, National Cancer Institute, Veterans Affairs, Jean Perkins Foundation, and Department of Defense. Dr. Garraway reported having no disclosures.

A version of this article appeared on Medscape.com.

Lowering the recommended age for baseline prostate-specific antigen (PSA) would reduce prostate cancer deaths by about 30% in Black men without significantly increasing the rate of overdiagnosis, according to new screening guidelines from the Prostate Cancer Foundation.

Specifically, baseline PSA testing in Black men should begin at age 40-45, sooner than current guidelines recommend, and should be followed by regular screening intervals, preferably annually, at least until age 70, a multidisciplinary panel of experts and patient advocates determined based on a comprehensive literature review.

The panel’s findings were presented in a poster at the ASCO Genitourinary Symposium.

“Black men in the United States are considered a high-risk population for being diagnosed with and dying from prostate cancer,” lead author Isla Garraway, MD, PhD, of the University of California, Los Angeles, and colleagues wrote. Specifically, Black men are about two times more likely to be diagnosed with and die from prostate cancer than White men. But, the authors continued, “few guidelines have outlined specific recommendations for PSA-based prostate cancer screening among Black men.”

The US Preventive Services Taskforce recommendations, which are currently being updated, set the PSA screening start age at 55. The task force recommendations, which dictate insurance coverage in the United States, acknowledged “a potential mortality benefit for African American men when beginning screening before age 55 years” but did not explicitly recommend screening earlier.

Current guidelines from the American Cancer Society call for discussions about screening in average-risk men to begin at age 50-55. The recommendations do specify lowering the age to 45 for those at a high risk for prostate cancer, which includes Black men as well as those with a first-degree relative diagnosed with prostate cancer before age 65. In some cases, screening can begin at age 40 in the highest risk men — those with more than one first-degree relative who had prostate cancer at a young age.

The Prostate Cancer Foundation “wanted to address the confusion around different guideline statements and the lack of clarity around screening recommendations for Black men,” said William K. Oh, MD, of The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York City, who chaired the panel for the new guidelines. “We thus convened a distinguished panel of experts from diverse backgrounds and expertise to create six guidelines statements to help Black men, their families, and their healthcare providers to consider options for prostate cancer screening based on the best available evidence.”

After reviewing 287, the expert panel developed six new guideline statements, reaching at least 80% consensus among panel members, addressing screening for Black men:

Because Black men are at a high risk for prostate cancer, the benefits of screening generally outweigh the risks.

PSA testing should be considered first line for prostate cancer screening, although some providers may recommend an optional digital rectal exam in addition to the PSA test.

Black men should engage in shared decision-making with their healthcare providers and other trusted sources of information to learn about the pros and cons of screening.

For Black men who elect screening, a baseline PSA test should be done between ages 40 and 45, and annual PSA screening should be strongly considered based on the PSA value and the individual’s health status.

Black men over age 70 who have been undergoing prostate cancer screening should talk with their healthcare provider about whether to continue PSA testing and make an informed decision based on their age, life expectancy, health status, family history, and prior PSA levels.

Black men who are at even higher risk due to a strong family history and/or known carriers of high-risk genetic variants should consider initiating annual PSA screening as early as age 40.

These statements are based on “the best available evidence, which overwhelmingly supports the conclusion that Black men in the US could benefit from a risk-adapted PSA screening,” the investigators concluded, noting that the latest evidence “warrants revisiting current recommendations for early [prostate cancer] detection in Black men from other national guideline groups.”

“We believe that the outcome of these more directed guidelines will be to give clarity to these men,” Dr. Oh added.

This research was funded by the Prostate Cancer Foundation, National Cancer Institute, Veterans Affairs, Jean Perkins Foundation, and Department of Defense. Dr. Garraway reported having no disclosures.

A version of this article appeared on Medscape.com.

The Stockholm3 (A3P Biomedical) multiparametic blood test has shown accuracy in assessing the risk of prostate cancer, exceeding that of the standard prostate-specific antigen (PSA)-based test, in Swedish patients. That improved accuracy was observed across diverse racial and ethnic groups, in a new study.

“The Stockholm3 outperformed the PSA test overall and in every subcohort, with an impressive reduction of unnecessary biopsies of 40% to 50%, while maintaining relative sensitivity,” first author Scott E. Eggener, MD, said in presenting the findings at the ASCO Genitourinary Cancers Symposium. The test “has attractive characteristics in a diverse cohort, including within various racial and ethnic subgroups,” added Dr. Eggener, professor of surgery and radiology at the University of Chicago.

While the PSA test, the standard-of-care in prostate cancer risk assessment, reduces mortality, the test is known to have a risk for false positive results, leading to unnecessary prostate biopsies, as well as overdiagnosis of low-risk prostate cancers, Dr. Eggener explained in his talk.

Randomized trials do show “fewer men die from prostate cancer with screening [with PSA testing], however, the likelihood of unnecessarily finding out about a cancer, undergoing treatment, and exposure to potential treatment-related side effects is significantly higher,” Dr. Eggener said in a interview.

The Stockholm3 clinical diagnostic prostate cancer test, which has been used in Sweden and Norway since 2017, was validated in a sample of nearly 60,000 men in the STHLM3 study (doi: 10.1016/S1470-2045[15]00361-7), which was published in The Lancet Oncology in December 2015. That study showed significant improvement over PSA alone detection of prostate cancers with a Gleason score of at least 7 (P < .0001), Dr. Eggener explained.

The test combines five plasma protein markers, including total and free PSA, PSP94, GDF-15 and KLK2, along with 101 genetic markers and clinical patient data, including age, previous biopsy results and family history.

Because the Stockholm3 test was validated in a Swedish population cohort, evidence on the accuracy of the test in other racial and ethnic populations is lacking, the authors noted in the abstract.

Study Methods and Results

To further investigate, Dr. Eggener and his colleagues conducted the prospective SEPTA trial, involving 2,129 men with no known prostate cancer but clinical indications for prostate biopsy, who were referred for prostate biopsy at 17 North American sites between 2019 and 2023.

Among the men, 24% were self-identified as African American/Black; 46% were White/Caucasian; 14% were Hispanic/Latina; and 16% were Asian. The men’s median age was 63; their median PSA value was 6.1 ng/mL, according to the abstract.

Of the patients, 16% received magnetic resonance imaging (MRI)-targeted biopsies and 20% had prior benign biopsies, the abstract notes.

Biopsy results showed that clinically significant prostate cancer, defined as International Society of Urological Pathology (ISUP) Gleason Grade group ≥ 2, was detected in 29% of patients, with 14% having ISUP 1 cancer and 57% of cases having been benign, according to the abstract.

Overall detection rates of grade 2 or higher were 37% for African American/Black, 28% for White/Caucasian, 29% for Hispanic/Latino, and 21% Asian.

In terms of sensitivity of the two tests, the Stockholm3 (cut-point of ≥ 15) was noninferior compared with the traditional PSA cut-point of ≥ 4 ng/mL (relative sensitivity 0.95).

Results were consistent across ethnic subgroups: noninferior sensitivity (0.91-0.98) and superior specificity (2.51-4.70), the abstract authors reported.

Compared with the use of the PSA test’s cut-point of ≥ 4 ng/mL, the use of Stockholm3’s cut-point of ≥ 15 or higher would have reduced unnecessary biopsies by 45% overall, including by 46% among Asian and Black/African American patients, by 53% in Hispanic patients and 42% in White patients, according to the abstract.

Overall, “utilization of Stockholm3 improves the net benefit:harm ratio of PSA screening by identifying nearly all men with Gleason Grade 2 or higher, while minimizing the number of men undergoing biopsy who show no cancer or an indolent cancer (Gleason Grade 1),” Dr. Eggener said in an interview.
 

Stockholm3 Expected to be Available in U.S. This Year

The test, which has been available in Sweden since 2018, is expected to become commercially available in the United States in early 2024. Dr. Eggener noted that “cost of the test hasn’t been finalized, but will be considerably more expensive than PSA, which is very cheap.”

Commenting on the findings, Bradley McGregor, MD, of the Dana Farber Cancer Institute and an ASCO oncology expert, noted that “ultimately, the goal [of prostate screening] is to be able to better decide when a biopsy is going to yield a clinically relevant prostate cancer, [and] this study gives us some insight of the use of the Stockholm3 tool in a more diverse population.

“How the tool will be utilized in the clinic and in guidelines is something that is a work in progress,” he added. “But I think this provides some reassurances that this will have implications beyond just the homogeneous populations in the original studies.”

Dr. McGregor noted that considerations of the issue of cost should be weighed against the potential costs involved in unnecessary biopsies and a host of other costs that can arise with an inaccurate risk assessment.

“If there is a way to avoid those costs and help us have more confidence in the prostate test results and intervene at an earlier stage, I think that’s exciting,” he said.

Dr. Eggener has consulted for A3P Biomedical but had no financial relationship with the company to disclose.

The Stockholm3 (A3P Biomedical) multiparametic blood test has shown accuracy in assessing the risk of prostate cancer, exceeding that of the standard prostate-specific antigen (PSA)-based test, in Swedish patients. That improved accuracy was observed across diverse racial and ethnic groups, in a new study.

“The Stockholm3 outperformed the PSA test overall and in every subcohort, with an impressive reduction of unnecessary biopsies of 40% to 50%, while maintaining relative sensitivity,” first author Scott E. Eggener, MD, said in presenting the findings at the ASCO Genitourinary Cancers Symposium. The test “has attractive characteristics in a diverse cohort, including within various racial and ethnic subgroups,” added Dr. Eggener, professor of surgery and radiology at the University of Chicago.

While the PSA test, the standard-of-care in prostate cancer risk assessment, reduces mortality, the test is known to have a risk for false positive results, leading to unnecessary prostate biopsies, as well as overdiagnosis of low-risk prostate cancers, Dr. Eggener explained in his talk.

Randomized trials do show “fewer men die from prostate cancer with screening [with PSA testing], however, the likelihood of unnecessarily finding out about a cancer, undergoing treatment, and exposure to potential treatment-related side effects is significantly higher,” Dr. Eggener said in a interview.

The Stockholm3 clinical diagnostic prostate cancer test, which has been used in Sweden and Norway since 2017, was validated in a sample of nearly 60,000 men in the STHLM3 study (doi: 10.1016/S1470-2045[15]00361-7), which was published in The Lancet Oncology in December 2015. That study showed significant improvement over PSA alone detection of prostate cancers with a Gleason score of at least 7 (P < .0001), Dr. Eggener explained.

The test combines five plasma protein markers, including total and free PSA, PSP94, GDF-15 and KLK2, along with 101 genetic markers and clinical patient data, including age, previous biopsy results and family history.

Because the Stockholm3 test was validated in a Swedish population cohort, evidence on the accuracy of the test in other racial and ethnic populations is lacking, the authors noted in the abstract.

Study Methods and Results

To further investigate, Dr. Eggener and his colleagues conducted the prospective SEPTA trial, involving 2,129 men with no known prostate cancer but clinical indications for prostate biopsy, who were referred for prostate biopsy at 17 North American sites between 2019 and 2023.

Among the men, 24% were self-identified as African American/Black; 46% were White/Caucasian; 14% were Hispanic/Latina; and 16% were Asian. The men’s median age was 63; their median PSA value was 6.1 ng/mL, according to the abstract.

Of the patients, 16% received magnetic resonance imaging (MRI)-targeted biopsies and 20% had prior benign biopsies, the abstract notes.

Biopsy results showed that clinically significant prostate cancer, defined as International Society of Urological Pathology (ISUP) Gleason Grade group ≥ 2, was detected in 29% of patients, with 14% having ISUP 1 cancer and 57% of cases having been benign, according to the abstract.

Overall detection rates of grade 2 or higher were 37% for African American/Black, 28% for White/Caucasian, 29% for Hispanic/Latino, and 21% Asian.

In terms of sensitivity of the two tests, the Stockholm3 (cut-point of ≥ 15) was noninferior compared with the traditional PSA cut-point of ≥ 4 ng/mL (relative sensitivity 0.95).

Results were consistent across ethnic subgroups: noninferior sensitivity (0.91-0.98) and superior specificity (2.51-4.70), the abstract authors reported.

Compared with the use of the PSA test’s cut-point of ≥ 4 ng/mL, the use of Stockholm3’s cut-point of ≥ 15 or higher would have reduced unnecessary biopsies by 45% overall, including by 46% among Asian and Black/African American patients, by 53% in Hispanic patients and 42% in White patients, according to the abstract.

Overall, “utilization of Stockholm3 improves the net benefit:harm ratio of PSA screening by identifying nearly all men with Gleason Grade 2 or higher, while minimizing the number of men undergoing biopsy who show no cancer or an indolent cancer (Gleason Grade 1),” Dr. Eggener said in an interview.
 

Stockholm3 Expected to be Available in U.S. This Year

The test, which has been available in Sweden since 2018, is expected to become commercially available in the United States in early 2024. Dr. Eggener noted that “cost of the test hasn’t been finalized, but will be considerably more expensive than PSA, which is very cheap.”

Commenting on the findings, Bradley McGregor, MD, of the Dana Farber Cancer Institute and an ASCO oncology expert, noted that “ultimately, the goal [of prostate screening] is to be able to better decide when a biopsy is going to yield a clinically relevant prostate cancer, [and] this study gives us some insight of the use of the Stockholm3 tool in a more diverse population.

“How the tool will be utilized in the clinic and in guidelines is something that is a work in progress,” he added. “But I think this provides some reassurances that this will have implications beyond just the homogeneous populations in the original studies.”

Dr. McGregor noted that considerations of the issue of cost should be weighed against the potential costs involved in unnecessary biopsies and a host of other costs that can arise with an inaccurate risk assessment.

“If there is a way to avoid those costs and help us have more confidence in the prostate test results and intervene at an earlier stage, I think that’s exciting,” he said.

Dr. Eggener has consulted for A3P Biomedical but had no financial relationship with the company to disclose.

The Stockholm3 (A3P Biomedical) multiparametic blood test has shown accuracy in assessing the risk of prostate cancer, exceeding that of the standard prostate-specific antigen (PSA)-based test, in Swedish patients. That improved accuracy was observed across diverse racial and ethnic groups, in a new study.

“The Stockholm3 outperformed the PSA test overall and in every subcohort, with an impressive reduction of unnecessary biopsies of 40% to 50%, while maintaining relative sensitivity,” first author Scott E. Eggener, MD, said in presenting the findings at the ASCO Genitourinary Cancers Symposium. The test “has attractive characteristics in a diverse cohort, including within various racial and ethnic subgroups,” added Dr. Eggener, professor of surgery and radiology at the University of Chicago.

While the PSA test, the standard-of-care in prostate cancer risk assessment, reduces mortality, the test is known to have a risk for false positive results, leading to unnecessary prostate biopsies, as well as overdiagnosis of low-risk prostate cancers, Dr. Eggener explained in his talk.

Randomized trials do show “fewer men die from prostate cancer with screening [with PSA testing], however, the likelihood of unnecessarily finding out about a cancer, undergoing treatment, and exposure to potential treatment-related side effects is significantly higher,” Dr. Eggener said in a interview.

The Stockholm3 clinical diagnostic prostate cancer test, which has been used in Sweden and Norway since 2017, was validated in a sample of nearly 60,000 men in the STHLM3 study (doi: 10.1016/S1470-2045[15]00361-7), which was published in The Lancet Oncology in December 2015. That study showed significant improvement over PSA alone detection of prostate cancers with a Gleason score of at least 7 (P < .0001), Dr. Eggener explained.

The test combines five plasma protein markers, including total and free PSA, PSP94, GDF-15 and KLK2, along with 101 genetic markers and clinical patient data, including age, previous biopsy results and family history.

Because the Stockholm3 test was validated in a Swedish population cohort, evidence on the accuracy of the test in other racial and ethnic populations is lacking, the authors noted in the abstract.

Study Methods and Results

To further investigate, Dr. Eggener and his colleagues conducted the prospective SEPTA trial, involving 2,129 men with no known prostate cancer but clinical indications for prostate biopsy, who were referred for prostate biopsy at 17 North American sites between 2019 and 2023.

Among the men, 24% were self-identified as African American/Black; 46% were White/Caucasian; 14% were Hispanic/Latina; and 16% were Asian. The men’s median age was 63; their median PSA value was 6.1 ng/mL, according to the abstract.

Of the patients, 16% received magnetic resonance imaging (MRI)-targeted biopsies and 20% had prior benign biopsies, the abstract notes.

Biopsy results showed that clinically significant prostate cancer, defined as International Society of Urological Pathology (ISUP) Gleason Grade group ≥ 2, was detected in 29% of patients, with 14% having ISUP 1 cancer and 57% of cases having been benign, according to the abstract.

Overall detection rates of grade 2 or higher were 37% for African American/Black, 28% for White/Caucasian, 29% for Hispanic/Latino, and 21% Asian.

In terms of sensitivity of the two tests, the Stockholm3 (cut-point of ≥ 15) was noninferior compared with the traditional PSA cut-point of ≥ 4 ng/mL (relative sensitivity 0.95).

Results were consistent across ethnic subgroups: noninferior sensitivity (0.91-0.98) and superior specificity (2.51-4.70), the abstract authors reported.

Compared with the use of the PSA test’s cut-point of ≥ 4 ng/mL, the use of Stockholm3’s cut-point of ≥ 15 or higher would have reduced unnecessary biopsies by 45% overall, including by 46% among Asian and Black/African American patients, by 53% in Hispanic patients and 42% in White patients, according to the abstract.

Overall, “utilization of Stockholm3 improves the net benefit:harm ratio of PSA screening by identifying nearly all men with Gleason Grade 2 or higher, while minimizing the number of men undergoing biopsy who show no cancer or an indolent cancer (Gleason Grade 1),” Dr. Eggener said in an interview.
 

Stockholm3 Expected to be Available in U.S. This Year

The test, which has been available in Sweden since 2018, is expected to become commercially available in the United States in early 2024. Dr. Eggener noted that “cost of the test hasn’t been finalized, but will be considerably more expensive than PSA, which is very cheap.”

Commenting on the findings, Bradley McGregor, MD, of the Dana Farber Cancer Institute and an ASCO oncology expert, noted that “ultimately, the goal [of prostate screening] is to be able to better decide when a biopsy is going to yield a clinically relevant prostate cancer, [and] this study gives us some insight of the use of the Stockholm3 tool in a more diverse population.

“How the tool will be utilized in the clinic and in guidelines is something that is a work in progress,” he added. “But I think this provides some reassurances that this will have implications beyond just the homogeneous populations in the original studies.”

Dr. McGregor noted that considerations of the issue of cost should be weighed against the potential costs involved in unnecessary biopsies and a host of other costs that can arise with an inaccurate risk assessment.

“If there is a way to avoid those costs and help us have more confidence in the prostate test results and intervene at an earlier stage, I think that’s exciting,” he said.

Dr. Eggener has consulted for A3P Biomedical but had no financial relationship with the company to disclose.

Men with localized prostate cancer face a number of treatment choices, including radical prostatectomy, radiotherapy with or without androgen deprivation therapy, and active surveillance. Understanding the likely functional outcomes of each treatment over time is important, as most patients are expected to live at least 15 years after diagnosis.

New research published Jan. 23 in JAMA parses functional outcome results from a population-based study of men diagnosed with localized prostate cancer. For their research, Bashir Al Hussein Al Awamlh, MD, of Vanderbilt University in Nashville, Tennessee, and his colleagues, looked at sexual function, urinary health, bowel function, hormonal function, and other outcomes in this cohort at 10 years’ follow-up.

Courtesy Vanderbilt University

Among 2455 patients for whom 10-year data were available, 1877 were deemed at baseline to have a favorable prognosis (defined as cT1-cT2bN0M0, prostate-specific antigen level less than 20 ng/mL, and grade group 1-2) and 568 had unfavorable-prognosis prostate cancer (defined as cT2cN0M0, prostate-specific antigen level of 20-50 ng/mL, or grade group 3-5). Follow-up data were collected by questionnaire through February 1, 2022. The men in the study were all younger than 80 years, and three-quarters of them were White.

At 10 years, outcomes differed based on the amount of time that had passed since diagnosis (they found different results at 3 and 5 year follow up, for example) and which treatment a patient received.

Among men with favorable prognoses at diagnosis, 20% underwent active surveillance for at least 1 year, while 56% received radical prostatectomy, 19% had external beam radiotherapy (EBRT) without ADT, and 5% had brachytherapy. Nearly a third of men originally opting for surveillance went on to undergo a therapeutic intervention by 10 years.

Dr. Al Hussein Al Awamlh and his colleagues found that while 3- and 5-year follow-up studies in this cohort had shown declines in sexual function among men who underwent surgery compared with those who had radiation or active surveillance, by 10 years those differences had faded, with no clinically meaningful differences in sexual function scores between the surgery and surveillance groups. In an interview, Dr. Al Hussein Al Awamlh said that this finding likely reflected mainly age-related declines in function across the study population — though it could also reflect declines after converting from surveillance to surgery or gradual decline with radiation treatment, he acknowledged.

Men with favorable prognoses at baseline who underwent surgery saw significantly worse urinary incontinence at 10 years compared with those started on radiotherapy or active surveillance. And EBRT was associated with fewer incontinence issues compared with active surveillance.

Among the group of men with an unfavorable prognosis at baseline, 64% of whom underwent radical prostatectomy and 36% EBRT with ADT, surgery was associated with worse urinary incontinence but not worse sexual function throughout 10 years of follow up, compared to radiotherapy with androgen deprivation therapy.

Radiation-treated patients with unfavorable prognoses, meanwhile, saw significantly worse bowel function and hormone function at 10 years compared with patients who had undergone surgery.

Dr. Al Hussein Al Awamlh said that a strength of this study was that “we had enough patients to stratify functional outcomes based on disease prognosis.” Another key finding was that some of the outcomes changed over time. “For example, among the patients with unfavorable prognoses, at 10-year follow-up there was slightly worse bowel and hormone function seen associated with radiation with ADT compared with surgery,” he said — something not seen at earlier follow-up points.

The findings may help offer a more nuanced way to counsel patients, Dr. Al Hussein Al Awamlh noted. For example, the side effects associated with sexual function “are not as relevant for those with unfavorable disease,” he said.

While current prostate cancer guidelines do address quality of life in shared decision-making, he said, “hopefully this data may provide more insight on that.” For patients with favorable prognosis, the findings reinforce that “active surveillance is a great option because it avoids the effects associated with those other treatments.”

Ultimately, Dr. Al Hussein Al Awamlh said, “this is a patient preference issue. It’s important for patients to understand how different functions are affected and to decide what is better for them — what they can live with and what they cannot, provided all the options are oncologically safe.”

The study authors disclosed as limitations of their study its observational design, the potential for response bias among study participants, and small numbers for some of the measured outcomes.

In an interview, urologist Mark S. Litwin, MD, of the University of California Los Angeles, characterized the study as “a well-conducted very-long-term longitudinal cohort that tracked men long past the initial diagnosis and treatment. That empowered the Vanderbilt team to find differences in quality of life many years later and compare them to other older men who had not received treatment.”

The new findings, Dr. Litwin said, “are critical in showing that most men with prostate cancer do not die from it; hence, the quality-of-life effects end up being the key issues for decision-making.”

Dr. Al Hussein Al Awamlh and colleagues’ study was funded by grants from the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Patient-Centered Outcomes Research Institute. Several coauthors disclosed funding from pharmaceutical and/or device manufacturers. Dr. Litwin disclosed no conflicts of interest related to his comment.

Men with localized prostate cancer face a number of treatment choices, including radical prostatectomy, radiotherapy with or without androgen deprivation therapy, and active surveillance. Understanding the likely functional outcomes of each treatment over time is important, as most patients are expected to live at least 15 years after diagnosis.

New research published Jan. 23 in JAMA parses functional outcome results from a population-based study of men diagnosed with localized prostate cancer. For their research, Bashir Al Hussein Al Awamlh, MD, of Vanderbilt University in Nashville, Tennessee, and his colleagues, looked at sexual function, urinary health, bowel function, hormonal function, and other outcomes in this cohort at 10 years’ follow-up.

Courtesy Vanderbilt University

Among 2455 patients for whom 10-year data were available, 1877 were deemed at baseline to have a favorable prognosis (defined as cT1-cT2bN0M0, prostate-specific antigen level less than 20 ng/mL, and grade group 1-2) and 568 had unfavorable-prognosis prostate cancer (defined as cT2cN0M0, prostate-specific antigen level of 20-50 ng/mL, or grade group 3-5). Follow-up data were collected by questionnaire through February 1, 2022. The men in the study were all younger than 80 years, and three-quarters of them were White.

At 10 years, outcomes differed based on the amount of time that had passed since diagnosis (they found different results at 3 and 5 year follow up, for example) and which treatment a patient received.

Among men with favorable prognoses at diagnosis, 20% underwent active surveillance for at least 1 year, while 56% received radical prostatectomy, 19% had external beam radiotherapy (EBRT) without ADT, and 5% had brachytherapy. Nearly a third of men originally opting for surveillance went on to undergo a therapeutic intervention by 10 years.

Dr. Al Hussein Al Awamlh and his colleagues found that while 3- and 5-year follow-up studies in this cohort had shown declines in sexual function among men who underwent surgery compared with those who had radiation or active surveillance, by 10 years those differences had faded, with no clinically meaningful differences in sexual function scores between the surgery and surveillance groups. In an interview, Dr. Al Hussein Al Awamlh said that this finding likely reflected mainly age-related declines in function across the study population — though it could also reflect declines after converting from surveillance to surgery or gradual decline with radiation treatment, he acknowledged.

Men with favorable prognoses at baseline who underwent surgery saw significantly worse urinary incontinence at 10 years compared with those started on radiotherapy or active surveillance. And EBRT was associated with fewer incontinence issues compared with active surveillance.

Among the group of men with an unfavorable prognosis at baseline, 64% of whom underwent radical prostatectomy and 36% EBRT with ADT, surgery was associated with worse urinary incontinence but not worse sexual function throughout 10 years of follow up, compared to radiotherapy with androgen deprivation therapy.

Radiation-treated patients with unfavorable prognoses, meanwhile, saw significantly worse bowel function and hormone function at 10 years compared with patients who had undergone surgery.

Dr. Al Hussein Al Awamlh said that a strength of this study was that “we had enough patients to stratify functional outcomes based on disease prognosis.” Another key finding was that some of the outcomes changed over time. “For example, among the patients with unfavorable prognoses, at 10-year follow-up there was slightly worse bowel and hormone function seen associated with radiation with ADT compared with surgery,” he said — something not seen at earlier follow-up points.

The findings may help offer a more nuanced way to counsel patients, Dr. Al Hussein Al Awamlh noted. For example, the side effects associated with sexual function “are not as relevant for those with unfavorable disease,” he said.

While current prostate cancer guidelines do address quality of life in shared decision-making, he said, “hopefully this data may provide more insight on that.” For patients with favorable prognosis, the findings reinforce that “active surveillance is a great option because it avoids the effects associated with those other treatments.”

Ultimately, Dr. Al Hussein Al Awamlh said, “this is a patient preference issue. It’s important for patients to understand how different functions are affected and to decide what is better for them — what they can live with and what they cannot, provided all the options are oncologically safe.”

The study authors disclosed as limitations of their study its observational design, the potential for response bias among study participants, and small numbers for some of the measured outcomes.

In an interview, urologist Mark S. Litwin, MD, of the University of California Los Angeles, characterized the study as “a well-conducted very-long-term longitudinal cohort that tracked men long past the initial diagnosis and treatment. That empowered the Vanderbilt team to find differences in quality of life many years later and compare them to other older men who had not received treatment.”

The new findings, Dr. Litwin said, “are critical in showing that most men with prostate cancer do not die from it; hence, the quality-of-life effects end up being the key issues for decision-making.”

Dr. Al Hussein Al Awamlh and colleagues’ study was funded by grants from the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Patient-Centered Outcomes Research Institute. Several coauthors disclosed funding from pharmaceutical and/or device manufacturers. Dr. Litwin disclosed no conflicts of interest related to his comment.

Men with localized prostate cancer face a number of treatment choices, including radical prostatectomy, radiotherapy with or without androgen deprivation therapy, and active surveillance. Understanding the likely functional outcomes of each treatment over time is important, as most patients are expected to live at least 15 years after diagnosis.

New research published Jan. 23 in JAMA parses functional outcome results from a population-based study of men diagnosed with localized prostate cancer. For their research, Bashir Al Hussein Al Awamlh, MD, of Vanderbilt University in Nashville, Tennessee, and his colleagues, looked at sexual function, urinary health, bowel function, hormonal function, and other outcomes in this cohort at 10 years’ follow-up.

Courtesy Vanderbilt University

Among 2455 patients for whom 10-year data were available, 1877 were deemed at baseline to have a favorable prognosis (defined as cT1-cT2bN0M0, prostate-specific antigen level less than 20 ng/mL, and grade group 1-2) and 568 had unfavorable-prognosis prostate cancer (defined as cT2cN0M0, prostate-specific antigen level of 20-50 ng/mL, or grade group 3-5). Follow-up data were collected by questionnaire through February 1, 2022. The men in the study were all younger than 80 years, and three-quarters of them were White.

At 10 years, outcomes differed based on the amount of time that had passed since diagnosis (they found different results at 3 and 5 year follow up, for example) and which treatment a patient received.

Among men with favorable prognoses at diagnosis, 20% underwent active surveillance for at least 1 year, while 56% received radical prostatectomy, 19% had external beam radiotherapy (EBRT) without ADT, and 5% had brachytherapy. Nearly a third of men originally opting for surveillance went on to undergo a therapeutic intervention by 10 years.

Dr. Al Hussein Al Awamlh and his colleagues found that while 3- and 5-year follow-up studies in this cohort had shown declines in sexual function among men who underwent surgery compared with those who had radiation or active surveillance, by 10 years those differences had faded, with no clinically meaningful differences in sexual function scores between the surgery and surveillance groups. In an interview, Dr. Al Hussein Al Awamlh said that this finding likely reflected mainly age-related declines in function across the study population — though it could also reflect declines after converting from surveillance to surgery or gradual decline with radiation treatment, he acknowledged.

Men with favorable prognoses at baseline who underwent surgery saw significantly worse urinary incontinence at 10 years compared with those started on radiotherapy or active surveillance. And EBRT was associated with fewer incontinence issues compared with active surveillance.

Among the group of men with an unfavorable prognosis at baseline, 64% of whom underwent radical prostatectomy and 36% EBRT with ADT, surgery was associated with worse urinary incontinence but not worse sexual function throughout 10 years of follow up, compared to radiotherapy with androgen deprivation therapy.

Radiation-treated patients with unfavorable prognoses, meanwhile, saw significantly worse bowel function and hormone function at 10 years compared with patients who had undergone surgery.

Dr. Al Hussein Al Awamlh said that a strength of this study was that “we had enough patients to stratify functional outcomes based on disease prognosis.” Another key finding was that some of the outcomes changed over time. “For example, among the patients with unfavorable prognoses, at 10-year follow-up there was slightly worse bowel and hormone function seen associated with radiation with ADT compared with surgery,” he said — something not seen at earlier follow-up points.

The findings may help offer a more nuanced way to counsel patients, Dr. Al Hussein Al Awamlh noted. For example, the side effects associated with sexual function “are not as relevant for those with unfavorable disease,” he said.

While current prostate cancer guidelines do address quality of life in shared decision-making, he said, “hopefully this data may provide more insight on that.” For patients with favorable prognosis, the findings reinforce that “active surveillance is a great option because it avoids the effects associated with those other treatments.”

Ultimately, Dr. Al Hussein Al Awamlh said, “this is a patient preference issue. It’s important for patients to understand how different functions are affected and to decide what is better for them — what they can live with and what they cannot, provided all the options are oncologically safe.”

The study authors disclosed as limitations of their study its observational design, the potential for response bias among study participants, and small numbers for some of the measured outcomes.

In an interview, urologist Mark S. Litwin, MD, of the University of California Los Angeles, characterized the study as “a well-conducted very-long-term longitudinal cohort that tracked men long past the initial diagnosis and treatment. That empowered the Vanderbilt team to find differences in quality of life many years later and compare them to other older men who had not received treatment.”

The new findings, Dr. Litwin said, “are critical in showing that most men with prostate cancer do not die from it; hence, the quality-of-life effects end up being the key issues for decision-making.”

Dr. Al Hussein Al Awamlh and colleagues’ study was funded by grants from the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Patient-Centered Outcomes Research Institute. Several coauthors disclosed funding from pharmaceutical and/or device manufacturers. Dr. Litwin disclosed no conflicts of interest related to his comment.

The report from the 2023 annual conference of French Urology Association (AFU), which was dedicated to male fertility, focused heavily on the diagnosis and treatment of varicocele, the most common reversible cause of infertility in men. Long a controversial subject, it has now been determined that treating this condition improves sperm analysis results, spontaneous fertility, and outcomes from medically assisted reproduction techniques. The AFU’s conference was a chance to present an overall snapshot of the issue.

Between 1973 and 2018, male sperm concentration dropped by 51.6% around the world, whereas total sperm counts dropped by 62.3%, according to Charlotte Methorst, MD, urological surgeon in Saint Cloud, France, president of the French Language Andrology Society, and coordinator of the AFU 2023 Report on Male Fertility. What’s more, sperm plasma concentrations are going down year-on-year at a rate twice as fast since before 2000 compared with the post-1972 period (from 1.16% to 2.64%).
 

Declining Fertility

Nowadays, around 15% of couples experience infertility (60,000 new cases/year in France). About 20% of these are strictly attributed to male infertility and 40% are mixed, implying a male factor. Consequently, Dr. Methorst explained that “we must routinely assess male fertility within the context of a medically assisted reproduction (MAR) pathway, without limiting testing to semen analysis. Varicocele, one of the causes of infertility that men should be screened for and defined as an abnormal and/or tortuous enlargement of the pampiniform plexus veins, is present in 15%-20% of the overall male population, 35% of men with primary infertility, and more than 70% of those experiencing secondary infertility.”

In infertile men, varicocele is mostly unilateral, occurring on the left side (85%-90% of cases). A link has been established between varicocele and insufficiency at the saphenofemoral junction, as well as venous insufficiency of the lower limbs (odds ratio, 2.34; P < .0001), suggesting a predisposition towards a vascular network favoring the presence of varicoceles.
 

Varicocele Underdiagnosed

Analysis of a large multicenter database recently suggested the underdiagnosis of varicocele in men being assessed for infertility. Diagnosis is primarily based on physical examination, with physicians finding a soft, serpiginous swelling in the upper and posterior part of the affected side of the scrotum. Testicular Doppler ultrasonography provides confirmation of a varicocele, taking into account aspects such as size and reflux duration during the Valsalva maneuver. Generally, this is enough to make a differential diagnosis, but MRI may be considered, especially in cases where a millimeter-sized nodule is also found.
 

Reversal Improves Fertility

A Cochrane meta-analysis, despite containing significant bias, raised doubts about the efficacy of varicocele treatment. Nevertheless, over the past 10 years, a randomized trial and several meta-analyses have put an end to the controversy, confirming that treatment for varicocele significantly improves natural pregnancy rates.

Microscopic subinguinal varicocelectomy is the gold-standard option for cases of clinical varicocele and for those in which sperm analysis findings are abnormal. This approach is associated with superior efficacy outcomes, such as improvement in sperm analysis results and pregnancy rates while leading to lower rates of recurrence (< 4%) and a favorable outcome in terms of complications. It should be noted that treating subclinical varicocele is not recommended.

Specifically, microscopic subinguinal varicocelectomy improves live birth and pregnancy rates, both naturally and via in vitro fertilization. What’s more, it has a positive impact on sperm count, total and progressive motility, morphology, and DNA fragmentation levels. Overall, this surgery changes the MAR approach used in around one in two cases. The grade and unilateral or bilateral nature of varicocele are important predictive factors of improvement in sperm analysis findings and pregnancy rates associated with this interventional procedure. Treating clinical varicocele (grades 1-3) leads to improved sperm analysis results, observed in 60%-70% of cases. According to a meta-analysis, the mean increase is said to be a concentration of 12 million spermatozoids per milliliter, as well as a mean improvement of 11% in sperm motility.

Notably, embolization can be considered as an alternative to surgery. This minimally invasive X-ray-guided procedure performed by an interventional radiologist attempts to block the dilated testicular vein.

Guidelines for clinical practice in treating varicocele were recently published by the AFU’s Andrology committee.

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

The report from the 2023 annual conference of French Urology Association (AFU), which was dedicated to male fertility, focused heavily on the diagnosis and treatment of varicocele, the most common reversible cause of infertility in men. Long a controversial subject, it has now been determined that treating this condition improves sperm analysis results, spontaneous fertility, and outcomes from medically assisted reproduction techniques. The AFU’s conference was a chance to present an overall snapshot of the issue.

Between 1973 and 2018, male sperm concentration dropped by 51.6% around the world, whereas total sperm counts dropped by 62.3%, according to Charlotte Methorst, MD, urological surgeon in Saint Cloud, France, president of the French Language Andrology Society, and coordinator of the AFU 2023 Report on Male Fertility. What’s more, sperm plasma concentrations are going down year-on-year at a rate twice as fast since before 2000 compared with the post-1972 period (from 1.16% to 2.64%).
 

Declining Fertility

Nowadays, around 15% of couples experience infertility (60,000 new cases/year in France). About 20% of these are strictly attributed to male infertility and 40% are mixed, implying a male factor. Consequently, Dr. Methorst explained that “we must routinely assess male fertility within the context of a medically assisted reproduction (MAR) pathway, without limiting testing to semen analysis. Varicocele, one of the causes of infertility that men should be screened for and defined as an abnormal and/or tortuous enlargement of the pampiniform plexus veins, is present in 15%-20% of the overall male population, 35% of men with primary infertility, and more than 70% of those experiencing secondary infertility.”

In infertile men, varicocele is mostly unilateral, occurring on the left side (85%-90% of cases). A link has been established between varicocele and insufficiency at the saphenofemoral junction, as well as venous insufficiency of the lower limbs (odds ratio, 2.34; P < .0001), suggesting a predisposition towards a vascular network favoring the presence of varicoceles.
 

Varicocele Underdiagnosed

Analysis of a large multicenter database recently suggested the underdiagnosis of varicocele in men being assessed for infertility. Diagnosis is primarily based on physical examination, with physicians finding a soft, serpiginous swelling in the upper and posterior part of the affected side of the scrotum. Testicular Doppler ultrasonography provides confirmation of a varicocele, taking into account aspects such as size and reflux duration during the Valsalva maneuver. Generally, this is enough to make a differential diagnosis, but MRI may be considered, especially in cases where a millimeter-sized nodule is also found.
 

Reversal Improves Fertility

A Cochrane meta-analysis, despite containing significant bias, raised doubts about the efficacy of varicocele treatment. Nevertheless, over the past 10 years, a randomized trial and several meta-analyses have put an end to the controversy, confirming that treatment for varicocele significantly improves natural pregnancy rates.

Microscopic subinguinal varicocelectomy is the gold-standard option for cases of clinical varicocele and for those in which sperm analysis findings are abnormal. This approach is associated with superior efficacy outcomes, such as improvement in sperm analysis results and pregnancy rates while leading to lower rates of recurrence (< 4%) and a favorable outcome in terms of complications. It should be noted that treating subclinical varicocele is not recommended.

Specifically, microscopic subinguinal varicocelectomy improves live birth and pregnancy rates, both naturally and via in vitro fertilization. What’s more, it has a positive impact on sperm count, total and progressive motility, morphology, and DNA fragmentation levels. Overall, this surgery changes the MAR approach used in around one in two cases. The grade and unilateral or bilateral nature of varicocele are important predictive factors of improvement in sperm analysis findings and pregnancy rates associated with this interventional procedure. Treating clinical varicocele (grades 1-3) leads to improved sperm analysis results, observed in 60%-70% of cases. According to a meta-analysis, the mean increase is said to be a concentration of 12 million spermatozoids per milliliter, as well as a mean improvement of 11% in sperm motility.

Notably, embolization can be considered as an alternative to surgery. This minimally invasive X-ray-guided procedure performed by an interventional radiologist attempts to block the dilated testicular vein.

Guidelines for clinical practice in treating varicocele were recently published by the AFU’s Andrology committee.

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

The report from the 2023 annual conference of French Urology Association (AFU), which was dedicated to male fertility, focused heavily on the diagnosis and treatment of varicocele, the most common reversible cause of infertility in men. Long a controversial subject, it has now been determined that treating this condition improves sperm analysis results, spontaneous fertility, and outcomes from medically assisted reproduction techniques. The AFU’s conference was a chance to present an overall snapshot of the issue.

Between 1973 and 2018, male sperm concentration dropped by 51.6% around the world, whereas total sperm counts dropped by 62.3%, according to Charlotte Methorst, MD, urological surgeon in Saint Cloud, France, president of the French Language Andrology Society, and coordinator of the AFU 2023 Report on Male Fertility. What’s more, sperm plasma concentrations are going down year-on-year at a rate twice as fast since before 2000 compared with the post-1972 period (from 1.16% to 2.64%).
 

Declining Fertility

Nowadays, around 15% of couples experience infertility (60,000 new cases/year in France). About 20% of these are strictly attributed to male infertility and 40% are mixed, implying a male factor. Consequently, Dr. Methorst explained that “we must routinely assess male fertility within the context of a medically assisted reproduction (MAR) pathway, without limiting testing to semen analysis. Varicocele, one of the causes of infertility that men should be screened for and defined as an abnormal and/or tortuous enlargement of the pampiniform plexus veins, is present in 15%-20% of the overall male population, 35% of men with primary infertility, and more than 70% of those experiencing secondary infertility.”

In infertile men, varicocele is mostly unilateral, occurring on the left side (85%-90% of cases). A link has been established between varicocele and insufficiency at the saphenofemoral junction, as well as venous insufficiency of the lower limbs (odds ratio, 2.34; P < .0001), suggesting a predisposition towards a vascular network favoring the presence of varicoceles.
 

Varicocele Underdiagnosed

Analysis of a large multicenter database recently suggested the underdiagnosis of varicocele in men being assessed for infertility. Diagnosis is primarily based on physical examination, with physicians finding a soft, serpiginous swelling in the upper and posterior part of the affected side of the scrotum. Testicular Doppler ultrasonography provides confirmation of a varicocele, taking into account aspects such as size and reflux duration during the Valsalva maneuver. Generally, this is enough to make a differential diagnosis, but MRI may be considered, especially in cases where a millimeter-sized nodule is also found.
 

Reversal Improves Fertility

A Cochrane meta-analysis, despite containing significant bias, raised doubts about the efficacy of varicocele treatment. Nevertheless, over the past 10 years, a randomized trial and several meta-analyses have put an end to the controversy, confirming that treatment for varicocele significantly improves natural pregnancy rates.

Microscopic subinguinal varicocelectomy is the gold-standard option for cases of clinical varicocele and for those in which sperm analysis findings are abnormal. This approach is associated with superior efficacy outcomes, such as improvement in sperm analysis results and pregnancy rates while leading to lower rates of recurrence (< 4%) and a favorable outcome in terms of complications. It should be noted that treating subclinical varicocele is not recommended.

Specifically, microscopic subinguinal varicocelectomy improves live birth and pregnancy rates, both naturally and via in vitro fertilization. What’s more, it has a positive impact on sperm count, total and progressive motility, morphology, and DNA fragmentation levels. Overall, this surgery changes the MAR approach used in around one in two cases. The grade and unilateral or bilateral nature of varicocele are important predictive factors of improvement in sperm analysis findings and pregnancy rates associated with this interventional procedure. Treating clinical varicocele (grades 1-3) leads to improved sperm analysis results, observed in 60%-70% of cases. According to a meta-analysis, the mean increase is said to be a concentration of 12 million spermatozoids per milliliter, as well as a mean improvement of 11% in sperm motility.

Notably, embolization can be considered as an alternative to surgery. This minimally invasive X-ray-guided procedure performed by an interventional radiologist attempts to block the dilated testicular vein.

Guidelines for clinical practice in treating varicocele were recently published by the AFU’s Andrology committee.

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

TOPLINE:

In middle-aged and older men with hypogonadism, excluding those at high prostate cancer risk, testosterone replacement therapy (TRT) showed low rates of adverse prostate events, including cancer.

METHODOLOGY:

• Uncertainty and concern exist about a link between prostate cancer risk and testosterone levels. Most professional society guidelines recommend against TRT in men with a history of or an increased risk for prostate cancer.
• The Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men  included 5204 men (ages 45-80, 17% Black, 80% White), randomly assigned to receive testosterone gel or placebo.
• Men with a history of cardiovascular disease or increased cardiovascular risk were evaluated to exclude those at increased prostate cancer risk (fasting testosterone < 300 ng/dL, ≥ 1 hypogonadal symptoms).
• The primary prostate safety endpoint was high-grade prostate cancer incidence (Gleason score, ≥ 4 + 3).
• Secondary endpoints were incidences of any prostate cancer, acute urinary retention, invasive procedure for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms.

TAKEAWAY:

• During 14,304 person-years of follow-up, high-grade prostate cancer incidence did not differ significantly between the TRT and placebo (0.19% vs 0.12%; P = .51) groups.
• The incidences of prostate cancer, acute urinary retention, invasive procedures for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms were also similar between the groups.
• TRT did not lead to an increase in lower urinary tract symptoms.
• The increase in prostate-specific antigen (PSA) levels was higher in the TRT group than in the placebo group (P < .001). However, the between-group difference did not widen after 12 months.

IN PRACTICE:

For “clinicians and patients who are considering testosterone replacement therapy for hypogonadism,” wrote the authors, “the study’s findings will facilitate a more informed appraisal of the potential prostate risks of testosterone replacement therapy.”

SOURCE:

Shalender Bhasin, MB, BS, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, led the study. It was published online in JAMA Network Open.

LIMITATIONS:

• The study findings do not apply to men with known prostate cancer or higher PSA values or those without confirmed hypogonadism.
• Although the TRAVERSE study was longer than many contemporary trials, carcinogens may require many years to induce malignant neoplasms.
• The trial’s structured evaluation of men after PSA testing did not include prostate imaging or other biomarker tests, which could affect the decision to perform a biopsy.

DISCLOSURES:

This study was funded by a consortium of testosterone manufacturers led by AbbVie Inc with additional financial support from Endo Pharmaceuticals, Acerus Pharmaceuticals Corp, and Upsher-Smith Laboratories. Mr. Bhasin and two coauthors declared receiving grants, consulting and personal fees, and other ties with pharmaceutical and device companies and other sources.

A version of this article appeared on Medscape.com.

TOPLINE:

In middle-aged and older men with hypogonadism, excluding those at high prostate cancer risk, testosterone replacement therapy (TRT) showed low rates of adverse prostate events, including cancer.

METHODOLOGY:

• Uncertainty and concern exist about a link between prostate cancer risk and testosterone levels. Most professional society guidelines recommend against TRT in men with a history of or an increased risk for prostate cancer.
• The Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men  included 5204 men (ages 45-80, 17% Black, 80% White), randomly assigned to receive testosterone gel or placebo.
• Men with a history of cardiovascular disease or increased cardiovascular risk were evaluated to exclude those at increased prostate cancer risk (fasting testosterone < 300 ng/dL, ≥ 1 hypogonadal symptoms).
• The primary prostate safety endpoint was high-grade prostate cancer incidence (Gleason score, ≥ 4 + 3).
• Secondary endpoints were incidences of any prostate cancer, acute urinary retention, invasive procedure for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms.

TAKEAWAY:

• During 14,304 person-years of follow-up, high-grade prostate cancer incidence did not differ significantly between the TRT and placebo (0.19% vs 0.12%; P = .51) groups.
• The incidences of prostate cancer, acute urinary retention, invasive procedures for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms were also similar between the groups.
• TRT did not lead to an increase in lower urinary tract symptoms.
• The increase in prostate-specific antigen (PSA) levels was higher in the TRT group than in the placebo group (P < .001). However, the between-group difference did not widen after 12 months.

IN PRACTICE:

For “clinicians and patients who are considering testosterone replacement therapy for hypogonadism,” wrote the authors, “the study’s findings will facilitate a more informed appraisal of the potential prostate risks of testosterone replacement therapy.”

SOURCE:

Shalender Bhasin, MB, BS, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, led the study. It was published online in JAMA Network Open.

LIMITATIONS:

• The study findings do not apply to men with known prostate cancer or higher PSA values or those without confirmed hypogonadism.
• Although the TRAVERSE study was longer than many contemporary trials, carcinogens may require many years to induce malignant neoplasms.
• The trial’s structured evaluation of men after PSA testing did not include prostate imaging or other biomarker tests, which could affect the decision to perform a biopsy.

DISCLOSURES:

This study was funded by a consortium of testosterone manufacturers led by AbbVie Inc with additional financial support from Endo Pharmaceuticals, Acerus Pharmaceuticals Corp, and Upsher-Smith Laboratories. Mr. Bhasin and two coauthors declared receiving grants, consulting and personal fees, and other ties with pharmaceutical and device companies and other sources.

A version of this article appeared on Medscape.com.

TOPLINE:

In middle-aged and older men with hypogonadism, excluding those at high prostate cancer risk, testosterone replacement therapy (TRT) showed low rates of adverse prostate events, including cancer.

METHODOLOGY:

• Uncertainty and concern exist about a link between prostate cancer risk and testosterone levels. Most professional society guidelines recommend against TRT in men with a history of or an increased risk for prostate cancer.
• The Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men  included 5204 men (ages 45-80, 17% Black, 80% White), randomly assigned to receive testosterone gel or placebo.
• Men with a history of cardiovascular disease or increased cardiovascular risk were evaluated to exclude those at increased prostate cancer risk (fasting testosterone < 300 ng/dL, ≥ 1 hypogonadal symptoms).
• The primary prostate safety endpoint was high-grade prostate cancer incidence (Gleason score, ≥ 4 + 3).
• Secondary endpoints were incidences of any prostate cancer, acute urinary retention, invasive procedure for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms.

TAKEAWAY:

• During 14,304 person-years of follow-up, high-grade prostate cancer incidence did not differ significantly between the TRT and placebo (0.19% vs 0.12%; P = .51) groups.
• The incidences of prostate cancer, acute urinary retention, invasive procedures for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms were also similar between the groups.
• TRT did not lead to an increase in lower urinary tract symptoms.
• The increase in prostate-specific antigen (PSA) levels was higher in the TRT group than in the placebo group (P < .001). However, the between-group difference did not widen after 12 months.

IN PRACTICE:

For “clinicians and patients who are considering testosterone replacement therapy for hypogonadism,” wrote the authors, “the study’s findings will facilitate a more informed appraisal of the potential prostate risks of testosterone replacement therapy.”

SOURCE:

Shalender Bhasin, MB, BS, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, led the study. It was published online in JAMA Network Open.

LIMITATIONS:

• The study findings do not apply to men with known prostate cancer or higher PSA values or those without confirmed hypogonadism.
• Although the TRAVERSE study was longer than many contemporary trials, carcinogens may require many years to induce malignant neoplasms.
• The trial’s structured evaluation of men after PSA testing did not include prostate imaging or other biomarker tests, which could affect the decision to perform a biopsy.

DISCLOSURES:

This study was funded by a consortium of testosterone manufacturers led by AbbVie Inc with additional financial support from Endo Pharmaceuticals, Acerus Pharmaceuticals Corp, and Upsher-Smith Laboratories. Mr. Bhasin and two coauthors declared receiving grants, consulting and personal fees, and other ties with pharmaceutical and device companies and other sources.

A version of this article appeared on Medscape.com.

Intake of protein, especially from plants, in middle age is associated with higher odds of healthy aging and positive mental and physical health status in older women, a recent analysis of the Nurses’ Health Study (NHS) data suggests.

The study is said to be the first to examine the long-term impact of midlife protein consumption on later health status.

Writing in the American Journal of Clinical Nutrition, a team led by Andres V. Ardisson Korat, DSc, a nutritional epidemiologist at the USDA Human Nutrition Research Center on Aging at Tufts University in Boston, Massachusetts, found the following midlife protein–related odds ratios (ORs) for later healthy aging measured at ages 70-93.

For each 3% energy increment from various protein sources:

• 1.05 (95% confidence interval, 1.01-1.10) for total protein
• 1.07 (1.02-1.11) for animal protein
• 1.14 (1.06-1.23) for dairy protein
• 1.38 (1.24-1.54) for plant protein 

In substitution analyses, significant positive associations were observed for the isocaloric replacement of animal or dairy protein, carbohydrate, or fat with plant protein — with increased ORs for healthy aging of 1.22-1.58 for each 3% of energy replacement.

On the measure of physical function, for example, replacing calories from all macronutrient variables with equivalent calories from plant protein was associated with 20%-60% higher odds of having no physical function limitations. Plant protein was also associated with higher odds for good mental status.

“Other studies have looked at protein intake in older adults, but we felt midlife was a more relevant etiological window,” Dr. Ardisson Korat said in an interview. “Our findings generally align, however, with those of protein intake in older populations, which have shown that protein can reduce the risk of frailty.”

He added that the benefits of protein, especially from plant sources, would likely apply to men as well and increasing plant protein intake is not difficult. “If you want a snack during the day, eat a handful of nuts instead of potato chips,” he advised. And eating several meals a week featuring beans, peas, lentils, tofu, whole grains, or seeds is an easy way to boost dietary plant protein, which comes with health-promoting soluble and insoluble fiber as well as antioxidant and anti-inflammatory polyphenols and other phytochemicals.

Conversely, plant but not animal protein consumption in older adulthood was linked to a lower risk of frailty in a previous NHS trial.

Higher plant protein intake was associated with a better probability of achieving healthy aging defined by changes in functional impairments, self-reported health/vitality, mental health, and use of health services in the Spanish Seniors-Estudio Sobre Nutricion y Riesgo Cardiovascular.

In contrast, animal protein intake in middle adulthood has been linked to an increased risk of premature death from chronic diseases driven by cardiovascular disease mortality.

The present findings are consistent with those observed for protein intakes in older adulthood, Dr. Ardisson Korat said.

“This study underscores the health advantages for midlife adults consuming adequate dietary protein — particularly plant protein — as one component of pursuing a healthy lifestyle,” said Douglas R. Dirschl, MD, chair of orthopedic surgery at Baylor College of Medicine in Houston, Texas. Most Americans consume adequate amounts of protein, but according to Dr. Dirschl, who treats many older patients for osteoporotic fractures and other musculoskeletal conditions, many US diets are subpar in this nutrient.

While protein is essential for bone and muscle formation and maintenance, “a surprising number of Americans are protein deficient, even those who seem hale and are overweight,” he said.


 

Dietary Recommendations for Midlife Patients

Physicians should therefore advise midlife patients to meet or perhaps modestly exceed the recommended dietary allowance (RDA) for protein of 0.8 g/kg per day and to make plant protein a substantial component of daily dietary protein intake, Dr. Dirschl said.

Luke D. Kim, MD, MEd, a geriatrician at the Cleveland Clinic in Cleveland, Ohio, noted that patients with lower socioeconomic status or with difficulty in day-to-day functioning are likely to have suboptimal protein intake. Such patients may need encouragement to eat more protein. “But we should keep in mind that showing a higher associated odds ratio of better health with increased protein take does not mean causality,” he said.

According to Rachel L. Amdur, MD, an internist at Northwestern Medicine in Chicago, Illinois, the long-term follow-up data from the NHS are uniquely helpful. “Middle-aged persons may think they no longer need much dietary protein and need to be reminded. Sometimes eating carbohydrates is just easier,” she said in an interview. Physicians need to asses and counsel patients on nutrition at all stages of life. “As I tell my patients, it’s best to think of your future self now.”

In agreement is Louis J. Morledge, MD, an internist at Northwell Health in New York City. “I firmly counsel my patients about adequate and often increased protein intake in middle life. But this is always within a larger framework of overall nutritional health.” He added that middle-aged persons often find themselves “stuck in food ruts,” and one of his clinical focuses is to advise patients about the importance of healthier food choices so they can better adjust to mental, emotional, physical, and skeletal changes as they age.
 

Study Details

The NHS analysis drew on prospective data from 48,762 nurses under age 60 in 1984. Total protein, animal protein, dairy protein, and plant protein were derived from validated food-frequency questionnaires.

Adjusting for lifestyle, demographics, and health status, the investigators identified 3721 (7.6% of cohort) eligible participants. The mean age of participants at baseline was 48.6 years; 38.6% had body mass indexes (BMI; in kg/m²) greater than 25; 22.9% were current smokers; and 88.2% were married.

Healthy aging was defined as freedom from 11 major chronic diseases, good mental health, and no impairments in cognitive or physical function, as assessed in the 2014 or 2016 NHS participant questionnaires. Diseases/treatments included cancer, type 2 diabetes, myocardial infarction, coronary artery bypass graft or coronary angioplasty, congestive heart failure, stroke, kidney failure, chronic obstructive pulmonary disease, Parkinson disease, multiple sclerosis, and amyotrophic lateral sclerosis.

Mean total protein consumption as a percentage of energy was 18.3% (standard deviation 3%), slightly higher than the average 16% in the US diet. Of this, 13.3% derived from animals, 3.6% from dairy products, and 4.9% from plants.

Total protein intake was positively associated with higher education levels, being physically active, higher BMI, and a baseline history of hypertension and hypercholesterolemia. Conversely, total protein intake was inversely associated with intakes of total carbohydrates, nuts, alcohol, and sugar-sweetened beverages.

The associations between protein intake and healthy aging are complex and not fully understood, the authors stated.
 

Effects of Protein Intake

In studies of older adult populations lower protein intake has been associated with lean mass loss. Animal protein supplementation studies in older adults have shown lean mass gains potentially related to amino acid composition.

In terms of mechanisms, evidence suggests that protein-related activation of the rapamycin complex 1 pathway may play a role, the authors suggested. The activity of this signaling pathway decreases with age.

Rapamycin, a compound used to prevent organ transplant rejection, has been associated with delayed aging. In the body, dietary protein and exercise activate this pathway, thereby stimulating muscle protein synthesis and possibly improving physical function.

As for the differential associations of plant and animal protein on the chronic disease domain of the healthy aging phenotype, Dr. Ardisson Korat and coauthors said plant protein has been associated with favorable levels of important risk factors for cardiometabolic diseases, such as reduced LDL cholesterol, lower blood pressure, and insulin sensitivity, as well as decreased levels of proinflammatory markers.

Conversely, total and animal protein intakes have been positively associated with concentrations of insulin-like growth factor 1, which is implicated in the growth of malignant cells in breast and prostate tissue.

This study is the first step in evaluating the long-term health effect of protein intake in midlife, the relevant development window for most chronic conditions, the NHS study authors said. More research is needed, however, to corroborate the study findings in other populations and identify underlying mechanisms.

This study was supported by the USDA Agricultural Research Service and the National Institutes of Health. The authors reported no conflicts of interest. The commentators disclosed no relevant competing interests.

Intake of protein, especially from plants, in middle age is associated with higher odds of healthy aging and positive mental and physical health status in older women, a recent analysis of the Nurses’ Health Study (NHS) data suggests.

The study is said to be the first to examine the long-term impact of midlife protein consumption on later health status.

Writing in the American Journal of Clinical Nutrition, a team led by Andres V. Ardisson Korat, DSc, a nutritional epidemiologist at the USDA Human Nutrition Research Center on Aging at Tufts University in Boston, Massachusetts, found the following midlife protein–related odds ratios (ORs) for later healthy aging measured at ages 70-93.

For each 3% energy increment from various protein sources:

• 1.05 (95% confidence interval, 1.01-1.10) for total protein
• 1.07 (1.02-1.11) for animal protein
• 1.14 (1.06-1.23) for dairy protein
• 1.38 (1.24-1.54) for plant protein 

In substitution analyses, significant positive associations were observed for the isocaloric replacement of animal or dairy protein, carbohydrate, or fat with plant protein — with increased ORs for healthy aging of 1.22-1.58 for each 3% of energy replacement.

On the measure of physical function, for example, replacing calories from all macronutrient variables with equivalent calories from plant protein was associated with 20%-60% higher odds of having no physical function limitations. Plant protein was also associated with higher odds for good mental status.

“Other studies have looked at protein intake in older adults, but we felt midlife was a more relevant etiological window,” Dr. Ardisson Korat said in an interview. “Our findings generally align, however, with those of protein intake in older populations, which have shown that protein can reduce the risk of frailty.”

He added that the benefits of protein, especially from plant sources, would likely apply to men as well and increasing plant protein intake is not difficult. “If you want a snack during the day, eat a handful of nuts instead of potato chips,” he advised. And eating several meals a week featuring beans, peas, lentils, tofu, whole grains, or seeds is an easy way to boost dietary plant protein, which comes with health-promoting soluble and insoluble fiber as well as antioxidant and anti-inflammatory polyphenols and other phytochemicals.

Conversely, plant but not animal protein consumption in older adulthood was linked to a lower risk of frailty in a previous NHS trial.

Higher plant protein intake was associated with a better probability of achieving healthy aging defined by changes in functional impairments, self-reported health/vitality, mental health, and use of health services in the Spanish Seniors-Estudio Sobre Nutricion y Riesgo Cardiovascular.

In contrast, animal protein intake in middle adulthood has been linked to an increased risk of premature death from chronic diseases driven by cardiovascular disease mortality.

The present findings are consistent with those observed for protein intakes in older adulthood, Dr. Ardisson Korat said.

“This study underscores the health advantages for midlife adults consuming adequate dietary protein — particularly plant protein — as one component of pursuing a healthy lifestyle,” said Douglas R. Dirschl, MD, chair of orthopedic surgery at Baylor College of Medicine in Houston, Texas. Most Americans consume adequate amounts of protein, but according to Dr. Dirschl, who treats many older patients for osteoporotic fractures and other musculoskeletal conditions, many US diets are subpar in this nutrient.

While protein is essential for bone and muscle formation and maintenance, “a surprising number of Americans are protein deficient, even those who seem hale and are overweight,” he said.


 

Dietary Recommendations for Midlife Patients

Physicians should therefore advise midlife patients to meet or perhaps modestly exceed the recommended dietary allowance (RDA) for protein of 0.8 g/kg per day and to make plant protein a substantial component of daily dietary protein intake, Dr. Dirschl said.

Luke D. Kim, MD, MEd, a geriatrician at the Cleveland Clinic in Cleveland, Ohio, noted that patients with lower socioeconomic status or with difficulty in day-to-day functioning are likely to have suboptimal protein intake. Such patients may need encouragement to eat more protein. “But we should keep in mind that showing a higher associated odds ratio of better health with increased protein take does not mean causality,” he said.

According to Rachel L. Amdur, MD, an internist at Northwestern Medicine in Chicago, Illinois, the long-term follow-up data from the NHS are uniquely helpful. “Middle-aged persons may think they no longer need much dietary protein and need to be reminded. Sometimes eating carbohydrates is just easier,” she said in an interview. Physicians need to asses and counsel patients on nutrition at all stages of life. “As I tell my patients, it’s best to think of your future self now.”

In agreement is Louis J. Morledge, MD, an internist at Northwell Health in New York City. “I firmly counsel my patients about adequate and often increased protein intake in middle life. But this is always within a larger framework of overall nutritional health.” He added that middle-aged persons often find themselves “stuck in food ruts,” and one of his clinical focuses is to advise patients about the importance of healthier food choices so they can better adjust to mental, emotional, physical, and skeletal changes as they age.
 

Study Details

The NHS analysis drew on prospective data from 48,762 nurses under age 60 in 1984. Total protein, animal protein, dairy protein, and plant protein were derived from validated food-frequency questionnaires.

Adjusting for lifestyle, demographics, and health status, the investigators identified 3721 (7.6% of cohort) eligible participants. The mean age of participants at baseline was 48.6 years; 38.6% had body mass indexes (BMI; in kg/m²) greater than 25; 22.9% were current smokers; and 88.2% were married.

Healthy aging was defined as freedom from 11 major chronic diseases, good mental health, and no impairments in cognitive or physical function, as assessed in the 2014 or 2016 NHS participant questionnaires. Diseases/treatments included cancer, type 2 diabetes, myocardial infarction, coronary artery bypass graft or coronary angioplasty, congestive heart failure, stroke, kidney failure, chronic obstructive pulmonary disease, Parkinson disease, multiple sclerosis, and amyotrophic lateral sclerosis.

Mean total protein consumption as a percentage of energy was 18.3% (standard deviation 3%), slightly higher than the average 16% in the US diet. Of this, 13.3% derived from animals, 3.6% from dairy products, and 4.9% from plants.

Total protein intake was positively associated with higher education levels, being physically active, higher BMI, and a baseline history of hypertension and hypercholesterolemia. Conversely, total protein intake was inversely associated with intakes of total carbohydrates, nuts, alcohol, and sugar-sweetened beverages.

The associations between protein intake and healthy aging are complex and not fully understood, the authors stated.
 

Effects of Protein Intake

In studies of older adult populations lower protein intake has been associated with lean mass loss. Animal protein supplementation studies in older adults have shown lean mass gains potentially related to amino acid composition.

In terms of mechanisms, evidence suggests that protein-related activation of the rapamycin complex 1 pathway may play a role, the authors suggested. The activity of this signaling pathway decreases with age.

Rapamycin, a compound used to prevent organ transplant rejection, has been associated with delayed aging. In the body, dietary protein and exercise activate this pathway, thereby stimulating muscle protein synthesis and possibly improving physical function.

As for the differential associations of plant and animal protein on the chronic disease domain of the healthy aging phenotype, Dr. Ardisson Korat and coauthors said plant protein has been associated with favorable levels of important risk factors for cardiometabolic diseases, such as reduced LDL cholesterol, lower blood pressure, and insulin sensitivity, as well as decreased levels of proinflammatory markers.

Conversely, total and animal protein intakes have been positively associated with concentrations of insulin-like growth factor 1, which is implicated in the growth of malignant cells in breast and prostate tissue.

This study is the first step in evaluating the long-term health effect of protein intake in midlife, the relevant development window for most chronic conditions, the NHS study authors said. More research is needed, however, to corroborate the study findings in other populations and identify underlying mechanisms.

This study was supported by the USDA Agricultural Research Service and the National Institutes of Health. The authors reported no conflicts of interest. The commentators disclosed no relevant competing interests.

Intake of protein, especially from plants, in middle age is associated with higher odds of healthy aging and positive mental and physical health status in older women, a recent analysis of the Nurses’ Health Study (NHS) data suggests.

The study is said to be the first to examine the long-term impact of midlife protein consumption on later health status.

Writing in the American Journal of Clinical Nutrition, a team led by Andres V. Ardisson Korat, DSc, a nutritional epidemiologist at the USDA Human Nutrition Research Center on Aging at Tufts University in Boston, Massachusetts, found the following midlife protein–related odds ratios (ORs) for later healthy aging measured at ages 70-93.

For each 3% energy increment from various protein sources:

• 1.05 (95% confidence interval, 1.01-1.10) for total protein
• 1.07 (1.02-1.11) for animal protein
• 1.14 (1.06-1.23) for dairy protein
• 1.38 (1.24-1.54) for plant protein 

In substitution analyses, significant positive associations were observed for the isocaloric replacement of animal or dairy protein, carbohydrate, or fat with plant protein — with increased ORs for healthy aging of 1.22-1.58 for each 3% of energy replacement.

On the measure of physical function, for example, replacing calories from all macronutrient variables with equivalent calories from plant protein was associated with 20%-60% higher odds of having no physical function limitations. Plant protein was also associated with higher odds for good mental status.

“Other studies have looked at protein intake in older adults, but we felt midlife was a more relevant etiological window,” Dr. Ardisson Korat said in an interview. “Our findings generally align, however, with those of protein intake in older populations, which have shown that protein can reduce the risk of frailty.”

He added that the benefits of protein, especially from plant sources, would likely apply to men as well and increasing plant protein intake is not difficult. “If you want a snack during the day, eat a handful of nuts instead of potato chips,” he advised. And eating several meals a week featuring beans, peas, lentils, tofu, whole grains, or seeds is an easy way to boost dietary plant protein, which comes with health-promoting soluble and insoluble fiber as well as antioxidant and anti-inflammatory polyphenols and other phytochemicals.

Conversely, plant but not animal protein consumption in older adulthood was linked to a lower risk of frailty in a previous NHS trial.

Higher plant protein intake was associated with a better probability of achieving healthy aging defined by changes in functional impairments, self-reported health/vitality, mental health, and use of health services in the Spanish Seniors-Estudio Sobre Nutricion y Riesgo Cardiovascular.

In contrast, animal protein intake in middle adulthood has been linked to an increased risk of premature death from chronic diseases driven by cardiovascular disease mortality.

The present findings are consistent with those observed for protein intakes in older adulthood, Dr. Ardisson Korat said.

“This study underscores the health advantages for midlife adults consuming adequate dietary protein — particularly plant protein — as one component of pursuing a healthy lifestyle,” said Douglas R. Dirschl, MD, chair of orthopedic surgery at Baylor College of Medicine in Houston, Texas. Most Americans consume adequate amounts of protein, but according to Dr. Dirschl, who treats many older patients for osteoporotic fractures and other musculoskeletal conditions, many US diets are subpar in this nutrient.

While protein is essential for bone and muscle formation and maintenance, “a surprising number of Americans are protein deficient, even those who seem hale and are overweight,” he said.


 

Dietary Recommendations for Midlife Patients

Physicians should therefore advise midlife patients to meet or perhaps modestly exceed the recommended dietary allowance (RDA) for protein of 0.8 g/kg per day and to make plant protein a substantial component of daily dietary protein intake, Dr. Dirschl said.

Luke D. Kim, MD, MEd, a geriatrician at the Cleveland Clinic in Cleveland, Ohio, noted that patients with lower socioeconomic status or with difficulty in day-to-day functioning are likely to have suboptimal protein intake. Such patients may need encouragement to eat more protein. “But we should keep in mind that showing a higher associated odds ratio of better health with increased protein take does not mean causality,” he said.

According to Rachel L. Amdur, MD, an internist at Northwestern Medicine in Chicago, Illinois, the long-term follow-up data from the NHS are uniquely helpful. “Middle-aged persons may think they no longer need much dietary protein and need to be reminded. Sometimes eating carbohydrates is just easier,” she said in an interview. Physicians need to asses and counsel patients on nutrition at all stages of life. “As I tell my patients, it’s best to think of your future self now.”

In agreement is Louis J. Morledge, MD, an internist at Northwell Health in New York City. “I firmly counsel my patients about adequate and often increased protein intake in middle life. But this is always within a larger framework of overall nutritional health.” He added that middle-aged persons often find themselves “stuck in food ruts,” and one of his clinical focuses is to advise patients about the importance of healthier food choices so they can better adjust to mental, emotional, physical, and skeletal changes as they age.
 

Study Details

The NHS analysis drew on prospective data from 48,762 nurses under age 60 in 1984. Total protein, animal protein, dairy protein, and plant protein were derived from validated food-frequency questionnaires.

Adjusting for lifestyle, demographics, and health status, the investigators identified 3721 (7.6% of cohort) eligible participants. The mean age of participants at baseline was 48.6 years; 38.6% had body mass indexes (BMI; in kg/m²) greater than 25; 22.9% were current smokers; and 88.2% were married.

Healthy aging was defined as freedom from 11 major chronic diseases, good mental health, and no impairments in cognitive or physical function, as assessed in the 2014 or 2016 NHS participant questionnaires. Diseases/treatments included cancer, type 2 diabetes, myocardial infarction, coronary artery bypass graft or coronary angioplasty, congestive heart failure, stroke, kidney failure, chronic obstructive pulmonary disease, Parkinson disease, multiple sclerosis, and amyotrophic lateral sclerosis.

Mean total protein consumption as a percentage of energy was 18.3% (standard deviation 3%), slightly higher than the average 16% in the US diet. Of this, 13.3% derived from animals, 3.6% from dairy products, and 4.9% from plants.

Total protein intake was positively associated with higher education levels, being physically active, higher BMI, and a baseline history of hypertension and hypercholesterolemia. Conversely, total protein intake was inversely associated with intakes of total carbohydrates, nuts, alcohol, and sugar-sweetened beverages.

The associations between protein intake and healthy aging are complex and not fully understood, the authors stated.
 

Effects of Protein Intake

In studies of older adult populations lower protein intake has been associated with lean mass loss. Animal protein supplementation studies in older adults have shown lean mass gains potentially related to amino acid composition.

In terms of mechanisms, evidence suggests that protein-related activation of the rapamycin complex 1 pathway may play a role, the authors suggested. The activity of this signaling pathway decreases with age.

Rapamycin, a compound used to prevent organ transplant rejection, has been associated with delayed aging. In the body, dietary protein and exercise activate this pathway, thereby stimulating muscle protein synthesis and possibly improving physical function.

As for the differential associations of plant and animal protein on the chronic disease domain of the healthy aging phenotype, Dr. Ardisson Korat and coauthors said plant protein has been associated with favorable levels of important risk factors for cardiometabolic diseases, such as reduced LDL cholesterol, lower blood pressure, and insulin sensitivity, as well as decreased levels of proinflammatory markers.

Conversely, total and animal protein intakes have been positively associated with concentrations of insulin-like growth factor 1, which is implicated in the growth of malignant cells in breast and prostate tissue.

This study is the first step in evaluating the long-term health effect of protein intake in midlife, the relevant development window for most chronic conditions, the NHS study authors said. More research is needed, however, to corroborate the study findings in other populations and identify underlying mechanisms.

This study was supported by the USDA Agricultural Research Service and the National Institutes of Health. The authors reported no conflicts of interest. The commentators disclosed no relevant competing interests.

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

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

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

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

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

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

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

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

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

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

A version of this article appeared on Medscape.com.

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

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

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

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

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

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

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

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

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

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

A version of this article appeared on Medscape.com.

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

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

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

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

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

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

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

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

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

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

A version of this article appeared on Medscape.com.