PSMA-PET Detects Metastatic Disease in Prostate Cancer Patients With Negative Conventional Imaging

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TOPLINE: 

Prostate-specific membrane antigen (PSMA)–PET detected metastatic disease in 46% of patients with high-risk prostate cancer previously classified as nonmetastatic by conventional imaging. Results were positive in 84% of patients, with polymetastatic disease found in 24% of cases.

METHODOLOGY:

  • Recurrent nonmetastatic hormone-sensitive prostate cancer is characterized by increasing prostate-specific antigen (PSA) levels while naive or responsive to androgen deprivation therapy, without evidence of metastasis on conventional imaging.
  • A post hoc, retrospective, cross-sectional analysis included 182 patients from four prospective studies conducted from September 2016 to September 2021, with participants having recurrent prostate cancer after radical prostatectomy, definitive radiotherapy, or salvage radiotherapy.
  • Inclusion criteria encompassed PSA levels > 1.0 ng/mL after radical prostatectomy and salvage radiotherapy or > 2.0 ng/mL above nadir after definitive radiotherapy, PSA doubling time ≤ 9 months, and serum testosterone ≥ 150 ng/dL.
  • Researchers at the University of California, Los Angeles, performed Gallium-68-PSMA-11 PET/CT imaging with a median injection of 5.0 mCi and uptake time of 61 minutes, with 98% of patients receiving CT contrast.

TAKEAWAY:

  • PSMA-PET findings were positive in 80% of patients after radical prostatectomy, 92% after definitive radiotherapy, 85% after radical prostatectomy and salvage radiotherapy, and 84% overall (153 of 182 patients).
  • Distant metastatic disease was detected in 34% of patients after radical prostatectomy, 56% after definitive radiotherapy, 60% after radical prostatectomy and salvage radiotherapy, and 46% overall.
  • Polymetastatic disease (≥ 5 lesions) was identified in 19% of patients after radical prostatectomy, 36% after definitive radiotherapy, 23% after radical prostatectomy and salvage radiotherapy, and 24% overall.
  • According to the authors, these findings suggest that patients’ high-risk nonmetastatic hormone-sensitive prostate cancers are understaged by conventional imaging.

IN PRACTICE:

“In a cohort of patients with high-risk hormone-sensitive prostate cancer without evidence of metastatic disease by conventional imaging, PSMA-PET results were positive in 84% of patients, detected M1 disease stage in 46% of patients, and found polymetastatic disease in 24% of patients. ... The results challenge the interpretation of previous studies, such as the EMBARK trial, and support the evolving role of PSMA-PET for patient selection in clinical and trial interventions in prostate cancer,” the authors of the new paper wrote. “Further studies are needed to assess its independent prognostic value and use for treatment guidance.”

SOURCE:

This study was led by Adrien Holzgreve, MD, and Wesley R. Armstrong, BS, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles. It was published online on January 3 in JAMA Network Open.

LIMITATIONS:

The analysis included significantly fewer patients treated with combined radical prostatectomy and salvage radiotherapy than the original EMBARK trial (29% vs 49%). Patients in this study had a lower median PSA doubling time and serum PSA level at enrollment than those in the EMBARK study. The retrospective nature of this study precluded systematic baseline imaging that would be standard for clinical trial enrollment. Additionally, while PSMA-PET offers the best diagnostic accuracy for prostate cancer staging, it can produce false-positive findings, particularly in bone metastases, with a positive predictive value of 0.84% in biochemical recurrence.

DISCLOSURES:

Holzgreve reported receiving personal fees from ABX advanced biochemical compounds outside the submitted work. This study was supported by grants from the Deutsche Forschungsgemeinschaft, the Prostate Cancer Foundation, and the Society of Nuclear Medicine and Molecular Imaging. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

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TOPLINE: 

Prostate-specific membrane antigen (PSMA)–PET detected metastatic disease in 46% of patients with high-risk prostate cancer previously classified as nonmetastatic by conventional imaging. Results were positive in 84% of patients, with polymetastatic disease found in 24% of cases.

METHODOLOGY:

  • Recurrent nonmetastatic hormone-sensitive prostate cancer is characterized by increasing prostate-specific antigen (PSA) levels while naive or responsive to androgen deprivation therapy, without evidence of metastasis on conventional imaging.
  • A post hoc, retrospective, cross-sectional analysis included 182 patients from four prospective studies conducted from September 2016 to September 2021, with participants having recurrent prostate cancer after radical prostatectomy, definitive radiotherapy, or salvage radiotherapy.
  • Inclusion criteria encompassed PSA levels > 1.0 ng/mL after radical prostatectomy and salvage radiotherapy or > 2.0 ng/mL above nadir after definitive radiotherapy, PSA doubling time ≤ 9 months, and serum testosterone ≥ 150 ng/dL.
  • Researchers at the University of California, Los Angeles, performed Gallium-68-PSMA-11 PET/CT imaging with a median injection of 5.0 mCi and uptake time of 61 minutes, with 98% of patients receiving CT contrast.

TAKEAWAY:

  • PSMA-PET findings were positive in 80% of patients after radical prostatectomy, 92% after definitive radiotherapy, 85% after radical prostatectomy and salvage radiotherapy, and 84% overall (153 of 182 patients).
  • Distant metastatic disease was detected in 34% of patients after radical prostatectomy, 56% after definitive radiotherapy, 60% after radical prostatectomy and salvage radiotherapy, and 46% overall.
  • Polymetastatic disease (≥ 5 lesions) was identified in 19% of patients after radical prostatectomy, 36% after definitive radiotherapy, 23% after radical prostatectomy and salvage radiotherapy, and 24% overall.
  • According to the authors, these findings suggest that patients’ high-risk nonmetastatic hormone-sensitive prostate cancers are understaged by conventional imaging.

IN PRACTICE:

“In a cohort of patients with high-risk hormone-sensitive prostate cancer without evidence of metastatic disease by conventional imaging, PSMA-PET results were positive in 84% of patients, detected M1 disease stage in 46% of patients, and found polymetastatic disease in 24% of patients. ... The results challenge the interpretation of previous studies, such as the EMBARK trial, and support the evolving role of PSMA-PET for patient selection in clinical and trial interventions in prostate cancer,” the authors of the new paper wrote. “Further studies are needed to assess its independent prognostic value and use for treatment guidance.”

SOURCE:

This study was led by Adrien Holzgreve, MD, and Wesley R. Armstrong, BS, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles. It was published online on January 3 in JAMA Network Open.

LIMITATIONS:

The analysis included significantly fewer patients treated with combined radical prostatectomy and salvage radiotherapy than the original EMBARK trial (29% vs 49%). Patients in this study had a lower median PSA doubling time and serum PSA level at enrollment than those in the EMBARK study. The retrospective nature of this study precluded systematic baseline imaging that would be standard for clinical trial enrollment. Additionally, while PSMA-PET offers the best diagnostic accuracy for prostate cancer staging, it can produce false-positive findings, particularly in bone metastases, with a positive predictive value of 0.84% in biochemical recurrence.

DISCLOSURES:

Holzgreve reported receiving personal fees from ABX advanced biochemical compounds outside the submitted work. This study was supported by grants from the Deutsche Forschungsgemeinschaft, the Prostate Cancer Foundation, and the Society of Nuclear Medicine and Molecular Imaging. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE: 

Prostate-specific membrane antigen (PSMA)–PET detected metastatic disease in 46% of patients with high-risk prostate cancer previously classified as nonmetastatic by conventional imaging. Results were positive in 84% of patients, with polymetastatic disease found in 24% of cases.

METHODOLOGY:

  • Recurrent nonmetastatic hormone-sensitive prostate cancer is characterized by increasing prostate-specific antigen (PSA) levels while naive or responsive to androgen deprivation therapy, without evidence of metastasis on conventional imaging.
  • A post hoc, retrospective, cross-sectional analysis included 182 patients from four prospective studies conducted from September 2016 to September 2021, with participants having recurrent prostate cancer after radical prostatectomy, definitive radiotherapy, or salvage radiotherapy.
  • Inclusion criteria encompassed PSA levels > 1.0 ng/mL after radical prostatectomy and salvage radiotherapy or > 2.0 ng/mL above nadir after definitive radiotherapy, PSA doubling time ≤ 9 months, and serum testosterone ≥ 150 ng/dL.
  • Researchers at the University of California, Los Angeles, performed Gallium-68-PSMA-11 PET/CT imaging with a median injection of 5.0 mCi and uptake time of 61 minutes, with 98% of patients receiving CT contrast.

TAKEAWAY:

  • PSMA-PET findings were positive in 80% of patients after radical prostatectomy, 92% after definitive radiotherapy, 85% after radical prostatectomy and salvage radiotherapy, and 84% overall (153 of 182 patients).
  • Distant metastatic disease was detected in 34% of patients after radical prostatectomy, 56% after definitive radiotherapy, 60% after radical prostatectomy and salvage radiotherapy, and 46% overall.
  • Polymetastatic disease (≥ 5 lesions) was identified in 19% of patients after radical prostatectomy, 36% after definitive radiotherapy, 23% after radical prostatectomy and salvage radiotherapy, and 24% overall.
  • According to the authors, these findings suggest that patients’ high-risk nonmetastatic hormone-sensitive prostate cancers are understaged by conventional imaging.

IN PRACTICE:

“In a cohort of patients with high-risk hormone-sensitive prostate cancer without evidence of metastatic disease by conventional imaging, PSMA-PET results were positive in 84% of patients, detected M1 disease stage in 46% of patients, and found polymetastatic disease in 24% of patients. ... The results challenge the interpretation of previous studies, such as the EMBARK trial, and support the evolving role of PSMA-PET for patient selection in clinical and trial interventions in prostate cancer,” the authors of the new paper wrote. “Further studies are needed to assess its independent prognostic value and use for treatment guidance.”

SOURCE:

This study was led by Adrien Holzgreve, MD, and Wesley R. Armstrong, BS, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles. It was published online on January 3 in JAMA Network Open.

LIMITATIONS:

The analysis included significantly fewer patients treated with combined radical prostatectomy and salvage radiotherapy than the original EMBARK trial (29% vs 49%). Patients in this study had a lower median PSA doubling time and serum PSA level at enrollment than those in the EMBARK study. The retrospective nature of this study precluded systematic baseline imaging that would be standard for clinical trial enrollment. Additionally, while PSMA-PET offers the best diagnostic accuracy for prostate cancer staging, it can produce false-positive findings, particularly in bone metastases, with a positive predictive value of 0.84% in biochemical recurrence.

DISCLOSURES:

Holzgreve reported receiving personal fees from ABX advanced biochemical compounds outside the submitted work. This study was supported by grants from the Deutsche Forschungsgemeinschaft, the Prostate Cancer Foundation, and the Society of Nuclear Medicine and Molecular Imaging. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

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MRI-Guided SBRT Cuts Long-Term Toxicities in Prostate Cancer

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Tue, 12/31/2024 - 13:47

TOPLINE:

Aggressive margin reduction with MRI-guided stereotactic body radiotherapy (SBRT) led to a significantly lower incidence of late genitourinary and gastrointestinal toxicities at 2 years compared with CT-guided SBRT in men with localized prostate cancer, new data showed.

METHODOLOGY:

  • MRI-guided SBRT is known to reduce planning margins in prostate cancer and lead to less acute toxicity compared with standard CT-guided SBRT. However, the long-term benefits of the MRI-guided approach remain unclear.
  • To find out, researchers conducted the phase 3 MIRAGE trial, in which 156 patients with localized prostate cancer were randomly assigned to receive either MRI-guided SBRT with 2-mm margins or CT-guided SBRT with 4-mm margins.
  • The MIRAGE trial initially reported the primary outcome of acute genitourinary grade ≥ 2 toxicity within 90 days of SBRT.
  • In this secondary analysis, researchers evaluated physician-reported late genitourinary and gastrointestinal toxicity, along with changes in various patient-reported quality-of-life scores over a 2-year follow-up period.

TAKEAWAY:

  • Over a period of 2 years, MRI-guided SBRT was associated with a significantly lower cumulative incidence of grade ≥ 2 genitourinary toxicities compared with CT-guided SBRT (27% vs 51%; P = .004). Similar outcomes were noted for grade ≥ 2 gastrointestinal toxicities (1.4% with MRI vs 9.5% with CT; P = .025).
  • Fewer patients who received MRI-guided SBRT reported deterioration in urinary irritation between 6 and 24 months after radiotherapy — 14 of 73 patients (19.2%) in the MRI group vs 24 of 68 patients (35.3%) in the CT group (P = .031).
  • Patients receiving MRI-guided SBRT were also less likely to experience clinically relevant deterioration in bowel function (odds ratio [OR], 0.444; P = .035) and sexual health score (OR, 0.366; P = .03).
  • Between 6 and 24 months after radiotherapy, 26.4% of patients (19 of 72) in the MRI group vs 42.3% (30 of 71) in the CT group reported clinically relevant deterioration in bowel function.

IN PRACTICE:

“Our secondary analysis of a randomized trial revealed that aggressive planning for margin reduction with MRI guidance vs CT guidance for prostate SBRT led to lower physician-scored genitourinary and gastrointestinal toxicity and better bowel and sexual quality-of-life metrics over 2 years of follow-up,” the authors wrote.

SOURCE:

This study, led by Amar U. Kishan, University of California Los Angeles, was published online in European Urology.

LIMITATIONS:

The absence of blinding in this study may have influenced both physician-scored toxicity assessments and patient-reported quality-of-life outcomes. The MIRAGE trial was not specifically designed with sufficient statistical power to evaluate the secondary analyses presented in this study.

DISCLOSURES:

This study was supported by grants from the US Department of Defense. Several authors reported receiving grants or personal fees among other ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

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TOPLINE:

Aggressive margin reduction with MRI-guided stereotactic body radiotherapy (SBRT) led to a significantly lower incidence of late genitourinary and gastrointestinal toxicities at 2 years compared with CT-guided SBRT in men with localized prostate cancer, new data showed.

METHODOLOGY:

  • MRI-guided SBRT is known to reduce planning margins in prostate cancer and lead to less acute toxicity compared with standard CT-guided SBRT. However, the long-term benefits of the MRI-guided approach remain unclear.
  • To find out, researchers conducted the phase 3 MIRAGE trial, in which 156 patients with localized prostate cancer were randomly assigned to receive either MRI-guided SBRT with 2-mm margins or CT-guided SBRT with 4-mm margins.
  • The MIRAGE trial initially reported the primary outcome of acute genitourinary grade ≥ 2 toxicity within 90 days of SBRT.
  • In this secondary analysis, researchers evaluated physician-reported late genitourinary and gastrointestinal toxicity, along with changes in various patient-reported quality-of-life scores over a 2-year follow-up period.

TAKEAWAY:

  • Over a period of 2 years, MRI-guided SBRT was associated with a significantly lower cumulative incidence of grade ≥ 2 genitourinary toxicities compared with CT-guided SBRT (27% vs 51%; P = .004). Similar outcomes were noted for grade ≥ 2 gastrointestinal toxicities (1.4% with MRI vs 9.5% with CT; P = .025).
  • Fewer patients who received MRI-guided SBRT reported deterioration in urinary irritation between 6 and 24 months after radiotherapy — 14 of 73 patients (19.2%) in the MRI group vs 24 of 68 patients (35.3%) in the CT group (P = .031).
  • Patients receiving MRI-guided SBRT were also less likely to experience clinically relevant deterioration in bowel function (odds ratio [OR], 0.444; P = .035) and sexual health score (OR, 0.366; P = .03).
  • Between 6 and 24 months after radiotherapy, 26.4% of patients (19 of 72) in the MRI group vs 42.3% (30 of 71) in the CT group reported clinically relevant deterioration in bowel function.

IN PRACTICE:

“Our secondary analysis of a randomized trial revealed that aggressive planning for margin reduction with MRI guidance vs CT guidance for prostate SBRT led to lower physician-scored genitourinary and gastrointestinal toxicity and better bowel and sexual quality-of-life metrics over 2 years of follow-up,” the authors wrote.

SOURCE:

This study, led by Amar U. Kishan, University of California Los Angeles, was published online in European Urology.

LIMITATIONS:

The absence of blinding in this study may have influenced both physician-scored toxicity assessments and patient-reported quality-of-life outcomes. The MIRAGE trial was not specifically designed with sufficient statistical power to evaluate the secondary analyses presented in this study.

DISCLOSURES:

This study was supported by grants from the US Department of Defense. Several authors reported receiving grants or personal fees among other ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Aggressive margin reduction with MRI-guided stereotactic body radiotherapy (SBRT) led to a significantly lower incidence of late genitourinary and gastrointestinal toxicities at 2 years compared with CT-guided SBRT in men with localized prostate cancer, new data showed.

METHODOLOGY:

  • MRI-guided SBRT is known to reduce planning margins in prostate cancer and lead to less acute toxicity compared with standard CT-guided SBRT. However, the long-term benefits of the MRI-guided approach remain unclear.
  • To find out, researchers conducted the phase 3 MIRAGE trial, in which 156 patients with localized prostate cancer were randomly assigned to receive either MRI-guided SBRT with 2-mm margins or CT-guided SBRT with 4-mm margins.
  • The MIRAGE trial initially reported the primary outcome of acute genitourinary grade ≥ 2 toxicity within 90 days of SBRT.
  • In this secondary analysis, researchers evaluated physician-reported late genitourinary and gastrointestinal toxicity, along with changes in various patient-reported quality-of-life scores over a 2-year follow-up period.

TAKEAWAY:

  • Over a period of 2 years, MRI-guided SBRT was associated with a significantly lower cumulative incidence of grade ≥ 2 genitourinary toxicities compared with CT-guided SBRT (27% vs 51%; P = .004). Similar outcomes were noted for grade ≥ 2 gastrointestinal toxicities (1.4% with MRI vs 9.5% with CT; P = .025).
  • Fewer patients who received MRI-guided SBRT reported deterioration in urinary irritation between 6 and 24 months after radiotherapy — 14 of 73 patients (19.2%) in the MRI group vs 24 of 68 patients (35.3%) in the CT group (P = .031).
  • Patients receiving MRI-guided SBRT were also less likely to experience clinically relevant deterioration in bowel function (odds ratio [OR], 0.444; P = .035) and sexual health score (OR, 0.366; P = .03).
  • Between 6 and 24 months after radiotherapy, 26.4% of patients (19 of 72) in the MRI group vs 42.3% (30 of 71) in the CT group reported clinically relevant deterioration in bowel function.

IN PRACTICE:

“Our secondary analysis of a randomized trial revealed that aggressive planning for margin reduction with MRI guidance vs CT guidance for prostate SBRT led to lower physician-scored genitourinary and gastrointestinal toxicity and better bowel and sexual quality-of-life metrics over 2 years of follow-up,” the authors wrote.

SOURCE:

This study, led by Amar U. Kishan, University of California Los Angeles, was published online in European Urology.

LIMITATIONS:

The absence of blinding in this study may have influenced both physician-scored toxicity assessments and patient-reported quality-of-life outcomes. The MIRAGE trial was not specifically designed with sufficient statistical power to evaluate the secondary analyses presented in this study.

DISCLOSURES:

This study was supported by grants from the US Department of Defense. Several authors reported receiving grants or personal fees among other ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

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Coffee Consumption Linked to Specific Gut Bacterium

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TOPLINE:

Coffee consumption is associated with the abundance of the gut bacterium Lawsonibacter asaccharolyticus, suggesting that specific foods can affect the intestinal microbiome.

METHODOLOGY:

  • The researchers selected coffee as a model to investigate the interplay between specific foods and the intestinal microbial community.
  • They conducted a multicohort, multiomic analysis of US and UK populations with detailed dietary information from 22,867 participants, which they then integrated with public data from 211 cohorts comprising 54,198 participants.
  • They conducted various in vitro experiments to expand and validate their findings, including adding coffee to media containing the L asaccharolyticus species that had been isolated from human feces.

TAKEAWAY:

  • L asaccharolyticus is highly prevalent, with about fourfold higher average abundance in coffee drinkers, and its growth is stimulated in vitro by coffee supplementation.
  • The link between coffee consumption and the microbiome was highly reproducible across different populations (area under the curve, 0.89), driven largely by the presence and abundance of L asaccharolyticus.
  • Similar associations were found in analyses of data from 25 countries. The prevalence of the bacterium was high in European countries with high per capita coffee consumption, such as Luxembourg, Denmark, and Sweden, and very low in countries with low per capita coffee consumption, such as China, Argentina, and India.
  • Plasma metabolomics on 438 samples identified several metabolites enriched among coffee drinkers, with quinic acid and its potential derivatives associated with both coffee and L asaccharolyticus.

IN PRACTICE:

“Our study provides insights into how the gut microbiome potentially mediates the chemistry — and thus health benefits — of coffee,” the study authors wrote. “The microbial mechanisms underlying the metabolism of coffee are a step towards mapping the role of specific foods on the gut microbiome, and similar patterns of microorganism–food interactions for other dietary elements should be sought with systematic epidemiologic and metagenomic investigations.”

SOURCE:

Paolo Manghi, PhD, University of Trento, Italy, led the study, which was published online in Nature Microbiology.

LIMITATIONS:

The authors relied on food questionnaires to assess coffee intake. The study is observational, and the clinical implications are unknown.

DISCLOSURES:

This work was supported by ZOE, a biotech company, and TwinsUK, an adult twin registry funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation, the National Institute for Health and Care Research — Clinical Research Network and Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust in partnership with King’s College London. Manghi had no competing interests. Several other coauthors reported financial relationships with ZOE, and three are cofounders of the company.

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

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TOPLINE:

Coffee consumption is associated with the abundance of the gut bacterium Lawsonibacter asaccharolyticus, suggesting that specific foods can affect the intestinal microbiome.

METHODOLOGY:

  • The researchers selected coffee as a model to investigate the interplay between specific foods and the intestinal microbial community.
  • They conducted a multicohort, multiomic analysis of US and UK populations with detailed dietary information from 22,867 participants, which they then integrated with public data from 211 cohorts comprising 54,198 participants.
  • They conducted various in vitro experiments to expand and validate their findings, including adding coffee to media containing the L asaccharolyticus species that had been isolated from human feces.

TAKEAWAY:

  • L asaccharolyticus is highly prevalent, with about fourfold higher average abundance in coffee drinkers, and its growth is stimulated in vitro by coffee supplementation.
  • The link between coffee consumption and the microbiome was highly reproducible across different populations (area under the curve, 0.89), driven largely by the presence and abundance of L asaccharolyticus.
  • Similar associations were found in analyses of data from 25 countries. The prevalence of the bacterium was high in European countries with high per capita coffee consumption, such as Luxembourg, Denmark, and Sweden, and very low in countries with low per capita coffee consumption, such as China, Argentina, and India.
  • Plasma metabolomics on 438 samples identified several metabolites enriched among coffee drinkers, with quinic acid and its potential derivatives associated with both coffee and L asaccharolyticus.

IN PRACTICE:

“Our study provides insights into how the gut microbiome potentially mediates the chemistry — and thus health benefits — of coffee,” the study authors wrote. “The microbial mechanisms underlying the metabolism of coffee are a step towards mapping the role of specific foods on the gut microbiome, and similar patterns of microorganism–food interactions for other dietary elements should be sought with systematic epidemiologic and metagenomic investigations.”

SOURCE:

Paolo Manghi, PhD, University of Trento, Italy, led the study, which was published online in Nature Microbiology.

LIMITATIONS:

The authors relied on food questionnaires to assess coffee intake. The study is observational, and the clinical implications are unknown.

DISCLOSURES:

This work was supported by ZOE, a biotech company, and TwinsUK, an adult twin registry funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation, the National Institute for Health and Care Research — Clinical Research Network and Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust in partnership with King’s College London. Manghi had no competing interests. Several other coauthors reported financial relationships with ZOE, and three are cofounders of the company.

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

TOPLINE:

Coffee consumption is associated with the abundance of the gut bacterium Lawsonibacter asaccharolyticus, suggesting that specific foods can affect the intestinal microbiome.

METHODOLOGY:

  • The researchers selected coffee as a model to investigate the interplay between specific foods and the intestinal microbial community.
  • They conducted a multicohort, multiomic analysis of US and UK populations with detailed dietary information from 22,867 participants, which they then integrated with public data from 211 cohorts comprising 54,198 participants.
  • They conducted various in vitro experiments to expand and validate their findings, including adding coffee to media containing the L asaccharolyticus species that had been isolated from human feces.

TAKEAWAY:

  • L asaccharolyticus is highly prevalent, with about fourfold higher average abundance in coffee drinkers, and its growth is stimulated in vitro by coffee supplementation.
  • The link between coffee consumption and the microbiome was highly reproducible across different populations (area under the curve, 0.89), driven largely by the presence and abundance of L asaccharolyticus.
  • Similar associations were found in analyses of data from 25 countries. The prevalence of the bacterium was high in European countries with high per capita coffee consumption, such as Luxembourg, Denmark, and Sweden, and very low in countries with low per capita coffee consumption, such as China, Argentina, and India.
  • Plasma metabolomics on 438 samples identified several metabolites enriched among coffee drinkers, with quinic acid and its potential derivatives associated with both coffee and L asaccharolyticus.

IN PRACTICE:

“Our study provides insights into how the gut microbiome potentially mediates the chemistry — and thus health benefits — of coffee,” the study authors wrote. “The microbial mechanisms underlying the metabolism of coffee are a step towards mapping the role of specific foods on the gut microbiome, and similar patterns of microorganism–food interactions for other dietary elements should be sought with systematic epidemiologic and metagenomic investigations.”

SOURCE:

Paolo Manghi, PhD, University of Trento, Italy, led the study, which was published online in Nature Microbiology.

LIMITATIONS:

The authors relied on food questionnaires to assess coffee intake. The study is observational, and the clinical implications are unknown.

DISCLOSURES:

This work was supported by ZOE, a biotech company, and TwinsUK, an adult twin registry funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation, the National Institute for Health and Care Research — Clinical Research Network and Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust in partnership with King’s College London. Manghi had no competing interests. Several other coauthors reported financial relationships with ZOE, and three are cofounders of the company.

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

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Muscle-Building Supplements May Lead Young Men to Steroids

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Wed, 12/18/2024 - 10:55

TOPLINE:

Muscle-building dietary supplement (MBS) use among young men substantially increases the odds of subsequent anabolic-androgenic steroid (AAS) initiation. Users of MBS showed elevated odds of incident AAS use within 1-5 years, supporting the gateway hypothesis for escalating risk-taking behaviors to increase muscularity.

METHODOLOGY:

  • Analysis included data from two Growing Up Today Study prospective cohorts spanning 14 years (2007-2021).
  • Participants included 4073 cisgender boys and young men aged 10-27 years at baseline (mean age, 20.3 years).
  • Demographics showed 92.8% White participants and 7.2% other races or ethnicities.
  • Researchers assessed past-year substance use for muscle building, including protein supplements, creatine, amino acids, hydroxymethylbutyrate, and dehydroepiandrosterone.

TAKEAWAY:

  • Initial survey results showed 11.1% of respondents reported past-year muscle-building supplement use, and 0.4% reported AAS use.
  • Over the study period, 37.7% of respondents reported any past-year muscle-building supplement use, while 0.5% reported any past-year AAS use.
  • Analysis revealed muscle-building supplement users had (odds ratio [OR], 8.31; 95% CI, 2.59-26.73) higher odds of initiating AAS use by the next survey wave than nonusers.
  • Age (adjusted OR [AOR], 0.98; 95% CI, 0.85-1.12) and cohort (AOR, 0.83; 95% CI, 0.30-2.32) were not statistically significant factors.

IN PRACTICE:

“The health risks of MBS use are well documented, as inadequate federal regulation has resulted in a US MBS marketplace rife with inaccurate labeling and adulteration with toxic ingredients. Clinicians, coaches, and parents should counsel against MBS use. Future studies with larger and more diverse samples are needed,” wrote the authors of the study.

SOURCE:

The study was led by Abigail Bulens, Division of Adolescent and Young Adult Medicine, Boston Children’s Hospital in Boston. It was published online in JAMA Network Open.

LIMITATIONS:

The study had a wide CI around the OR, potentially affecting the precision of the risk estimates. Additionally, the sample lacked diversity, with 92.8% of participants being White, which may limit the generalizability of findings to other racial and ethnic groups.

DISCLOSURES:

One coauthor received support from grant 1F32MDO17452-01 from the National Institute on Minority Health and Health Disparities. Another coauthor received support from training grant T76-MC-00001 from the Maternal and Child Health Bureau, Health Resources and Services Administration, Department of Health and Human Services. The cohorts were supported by National Institutes of Health grants HD045763, HD057368, DK46834, and HLO3533. The funders had no role in the study design, data collection, analysis, interpretation, manuscript preparation, or publication decision.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

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TOPLINE:

Muscle-building dietary supplement (MBS) use among young men substantially increases the odds of subsequent anabolic-androgenic steroid (AAS) initiation. Users of MBS showed elevated odds of incident AAS use within 1-5 years, supporting the gateway hypothesis for escalating risk-taking behaviors to increase muscularity.

METHODOLOGY:

  • Analysis included data from two Growing Up Today Study prospective cohorts spanning 14 years (2007-2021).
  • Participants included 4073 cisgender boys and young men aged 10-27 years at baseline (mean age, 20.3 years).
  • Demographics showed 92.8% White participants and 7.2% other races or ethnicities.
  • Researchers assessed past-year substance use for muscle building, including protein supplements, creatine, amino acids, hydroxymethylbutyrate, and dehydroepiandrosterone.

TAKEAWAY:

  • Initial survey results showed 11.1% of respondents reported past-year muscle-building supplement use, and 0.4% reported AAS use.
  • Over the study period, 37.7% of respondents reported any past-year muscle-building supplement use, while 0.5% reported any past-year AAS use.
  • Analysis revealed muscle-building supplement users had (odds ratio [OR], 8.31; 95% CI, 2.59-26.73) higher odds of initiating AAS use by the next survey wave than nonusers.
  • Age (adjusted OR [AOR], 0.98; 95% CI, 0.85-1.12) and cohort (AOR, 0.83; 95% CI, 0.30-2.32) were not statistically significant factors.

IN PRACTICE:

“The health risks of MBS use are well documented, as inadequate federal regulation has resulted in a US MBS marketplace rife with inaccurate labeling and adulteration with toxic ingredients. Clinicians, coaches, and parents should counsel against MBS use. Future studies with larger and more diverse samples are needed,” wrote the authors of the study.

SOURCE:

The study was led by Abigail Bulens, Division of Adolescent and Young Adult Medicine, Boston Children’s Hospital in Boston. It was published online in JAMA Network Open.

LIMITATIONS:

The study had a wide CI around the OR, potentially affecting the precision of the risk estimates. Additionally, the sample lacked diversity, with 92.8% of participants being White, which may limit the generalizability of findings to other racial and ethnic groups.

DISCLOSURES:

One coauthor received support from grant 1F32MDO17452-01 from the National Institute on Minority Health and Health Disparities. Another coauthor received support from training grant T76-MC-00001 from the Maternal and Child Health Bureau, Health Resources and Services Administration, Department of Health and Human Services. The cohorts were supported by National Institutes of Health grants HD045763, HD057368, DK46834, and HLO3533. The funders had no role in the study design, data collection, analysis, interpretation, manuscript preparation, or publication decision.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Muscle-building dietary supplement (MBS) use among young men substantially increases the odds of subsequent anabolic-androgenic steroid (AAS) initiation. Users of MBS showed elevated odds of incident AAS use within 1-5 years, supporting the gateway hypothesis for escalating risk-taking behaviors to increase muscularity.

METHODOLOGY:

  • Analysis included data from two Growing Up Today Study prospective cohorts spanning 14 years (2007-2021).
  • Participants included 4073 cisgender boys and young men aged 10-27 years at baseline (mean age, 20.3 years).
  • Demographics showed 92.8% White participants and 7.2% other races or ethnicities.
  • Researchers assessed past-year substance use for muscle building, including protein supplements, creatine, amino acids, hydroxymethylbutyrate, and dehydroepiandrosterone.

TAKEAWAY:

  • Initial survey results showed 11.1% of respondents reported past-year muscle-building supplement use, and 0.4% reported AAS use.
  • Over the study period, 37.7% of respondents reported any past-year muscle-building supplement use, while 0.5% reported any past-year AAS use.
  • Analysis revealed muscle-building supplement users had (odds ratio [OR], 8.31; 95% CI, 2.59-26.73) higher odds of initiating AAS use by the next survey wave than nonusers.
  • Age (adjusted OR [AOR], 0.98; 95% CI, 0.85-1.12) and cohort (AOR, 0.83; 95% CI, 0.30-2.32) were not statistically significant factors.

IN PRACTICE:

“The health risks of MBS use are well documented, as inadequate federal regulation has resulted in a US MBS marketplace rife with inaccurate labeling and adulteration with toxic ingredients. Clinicians, coaches, and parents should counsel against MBS use. Future studies with larger and more diverse samples are needed,” wrote the authors of the study.

SOURCE:

The study was led by Abigail Bulens, Division of Adolescent and Young Adult Medicine, Boston Children’s Hospital in Boston. It was published online in JAMA Network Open.

LIMITATIONS:

The study had a wide CI around the OR, potentially affecting the precision of the risk estimates. Additionally, the sample lacked diversity, with 92.8% of participants being White, which may limit the generalizability of findings to other racial and ethnic groups.

DISCLOSURES:

One coauthor received support from grant 1F32MDO17452-01 from the National Institute on Minority Health and Health Disparities. Another coauthor received support from training grant T76-MC-00001 from the Maternal and Child Health Bureau, Health Resources and Services Administration, Department of Health and Human Services. The cohorts were supported by National Institutes of Health grants HD045763, HD057368, DK46834, and HLO3533. The funders had no role in the study design, data collection, analysis, interpretation, manuscript preparation, or publication decision.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

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How Are Patients Managing Intermediate-Risk Prostate Cancer?

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TOPLINE:

The use of active surveillance or watchful waiting increased by more than twofold overall between 2010 and 2020 among patients with intermediate-risk prostate cancer.

METHODOLOGY:

  • Current guidelines support active surveillance or watchful waiting for select patients with intermediate-risk prostate cancer. These observation strategies may help reduce the adverse effects associated with immediate radical treatment.
  • To understand the trends over time in the use of active surveillance and watchful waiting, researchers looked at data of 147,205 individuals with intermediate-risk prostate cancer from the Surveillance, Epidemiology, and End Results prostate cancer database between 2010 and 2020 in the United States.
  • Criteria for intermediate-risk included Gleason grade group 2 or 3, prostate-specific antigen (PSA) levels of 10-20 ng/mL, or stage cT2b of the disease. Researchers also included trends for patients with Gleason grade group 1, as a reference group.
  • Researchers assessed the temporal trends and factors associated with the selection of active surveillance and watchful waiting in this population.

TAKEAWAY:

  • Overall, the rate of active surveillance and watchful waiting more than doubled among intermediate-risk patients from 5% to 12.3% between 2010 and 2020.
  • Between 2010 and 2020, the use of active surveillance and watchful waiting increased significantly among patients in Gleason grade group 1 (13.2% to 53.8%) and Gleason grade group 2 (4.0% to 11.6%) but remained stable for those in Gleason grade group 3 (2.5% to 2.8%; P = .85). For those with PSA levels < 10 ng/mL, adoption increased from 3.4% in 2010 to 9.2% in 2020 and more than doubled (9.3% to 20.7%) for those with PSA levels of 10-20 ng/mL.
  • Higher Gleason grade groups had a significantly lower likelihood of adopting active surveillance or watchful waiting (Gleason grade group 2 vs 1: odds ratio [OR], 0.83; Gleason grade group 3 vs 1: OR, 0.79).
  • Hispanic or Latino individuals (OR, 0.98) and non-Hispanic Black individuals (OR, 0.99) were slightly less likely to adopt these strategies than non-Hispanic White individuals.

IN PRACTICE:

“This study found a significant increase in initial active surveillance and watchful waiting for intermediate-risk prostate cancer between 2010 and 2020,” the authors wrote. “Research priorities should include reducing upfront overdiagnosis and better defining criteria for starting and stopping active surveillance and watchful waiting beyond conventional clinical measures such as GGs [Gleason grade groups] or PSA levels alone.”

SOURCE:

This study, led by Ismail Ajjawi, Yale School of Medicine, New Haven, Connecticut, was published online in JAMA.

LIMITATIONS:

This study relied on observational data and therefore could not capture various factors influencing clinical decision-making processes. Additionally, the absence of information on patient outcomes restricted the ability to assess the long-term implications of different management strategies.

DISCLOSURES:

This study received financial support from the Urological Research Foundation. Several authors reported having various ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

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TOPLINE:

The use of active surveillance or watchful waiting increased by more than twofold overall between 2010 and 2020 among patients with intermediate-risk prostate cancer.

METHODOLOGY:

  • Current guidelines support active surveillance or watchful waiting for select patients with intermediate-risk prostate cancer. These observation strategies may help reduce the adverse effects associated with immediate radical treatment.
  • To understand the trends over time in the use of active surveillance and watchful waiting, researchers looked at data of 147,205 individuals with intermediate-risk prostate cancer from the Surveillance, Epidemiology, and End Results prostate cancer database between 2010 and 2020 in the United States.
  • Criteria for intermediate-risk included Gleason grade group 2 or 3, prostate-specific antigen (PSA) levels of 10-20 ng/mL, or stage cT2b of the disease. Researchers also included trends for patients with Gleason grade group 1, as a reference group.
  • Researchers assessed the temporal trends and factors associated with the selection of active surveillance and watchful waiting in this population.

TAKEAWAY:

  • Overall, the rate of active surveillance and watchful waiting more than doubled among intermediate-risk patients from 5% to 12.3% between 2010 and 2020.
  • Between 2010 and 2020, the use of active surveillance and watchful waiting increased significantly among patients in Gleason grade group 1 (13.2% to 53.8%) and Gleason grade group 2 (4.0% to 11.6%) but remained stable for those in Gleason grade group 3 (2.5% to 2.8%; P = .85). For those with PSA levels < 10 ng/mL, adoption increased from 3.4% in 2010 to 9.2% in 2020 and more than doubled (9.3% to 20.7%) for those with PSA levels of 10-20 ng/mL.
  • Higher Gleason grade groups had a significantly lower likelihood of adopting active surveillance or watchful waiting (Gleason grade group 2 vs 1: odds ratio [OR], 0.83; Gleason grade group 3 vs 1: OR, 0.79).
  • Hispanic or Latino individuals (OR, 0.98) and non-Hispanic Black individuals (OR, 0.99) were slightly less likely to adopt these strategies than non-Hispanic White individuals.

IN PRACTICE:

“This study found a significant increase in initial active surveillance and watchful waiting for intermediate-risk prostate cancer between 2010 and 2020,” the authors wrote. “Research priorities should include reducing upfront overdiagnosis and better defining criteria for starting and stopping active surveillance and watchful waiting beyond conventional clinical measures such as GGs [Gleason grade groups] or PSA levels alone.”

SOURCE:

This study, led by Ismail Ajjawi, Yale School of Medicine, New Haven, Connecticut, was published online in JAMA.

LIMITATIONS:

This study relied on observational data and therefore could not capture various factors influencing clinical decision-making processes. Additionally, the absence of information on patient outcomes restricted the ability to assess the long-term implications of different management strategies.

DISCLOSURES:

This study received financial support from the Urological Research Foundation. Several authors reported having various ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

The use of active surveillance or watchful waiting increased by more than twofold overall between 2010 and 2020 among patients with intermediate-risk prostate cancer.

METHODOLOGY:

  • Current guidelines support active surveillance or watchful waiting for select patients with intermediate-risk prostate cancer. These observation strategies may help reduce the adverse effects associated with immediate radical treatment.
  • To understand the trends over time in the use of active surveillance and watchful waiting, researchers looked at data of 147,205 individuals with intermediate-risk prostate cancer from the Surveillance, Epidemiology, and End Results prostate cancer database between 2010 and 2020 in the United States.
  • Criteria for intermediate-risk included Gleason grade group 2 or 3, prostate-specific antigen (PSA) levels of 10-20 ng/mL, or stage cT2b of the disease. Researchers also included trends for patients with Gleason grade group 1, as a reference group.
  • Researchers assessed the temporal trends and factors associated with the selection of active surveillance and watchful waiting in this population.

TAKEAWAY:

  • Overall, the rate of active surveillance and watchful waiting more than doubled among intermediate-risk patients from 5% to 12.3% between 2010 and 2020.
  • Between 2010 and 2020, the use of active surveillance and watchful waiting increased significantly among patients in Gleason grade group 1 (13.2% to 53.8%) and Gleason grade group 2 (4.0% to 11.6%) but remained stable for those in Gleason grade group 3 (2.5% to 2.8%; P = .85). For those with PSA levels < 10 ng/mL, adoption increased from 3.4% in 2010 to 9.2% in 2020 and more than doubled (9.3% to 20.7%) for those with PSA levels of 10-20 ng/mL.
  • Higher Gleason grade groups had a significantly lower likelihood of adopting active surveillance or watchful waiting (Gleason grade group 2 vs 1: odds ratio [OR], 0.83; Gleason grade group 3 vs 1: OR, 0.79).
  • Hispanic or Latino individuals (OR, 0.98) and non-Hispanic Black individuals (OR, 0.99) were slightly less likely to adopt these strategies than non-Hispanic White individuals.

IN PRACTICE:

“This study found a significant increase in initial active surveillance and watchful waiting for intermediate-risk prostate cancer between 2010 and 2020,” the authors wrote. “Research priorities should include reducing upfront overdiagnosis and better defining criteria for starting and stopping active surveillance and watchful waiting beyond conventional clinical measures such as GGs [Gleason grade groups] or PSA levels alone.”

SOURCE:

This study, led by Ismail Ajjawi, Yale School of Medicine, New Haven, Connecticut, was published online in JAMA.

LIMITATIONS:

This study relied on observational data and therefore could not capture various factors influencing clinical decision-making processes. Additionally, the absence of information on patient outcomes restricted the ability to assess the long-term implications of different management strategies.

DISCLOSURES:

This study received financial support from the Urological Research Foundation. Several authors reported having various ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

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Diet Matters in Prostate Cancer, but It’s Complicated

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Diet is increasingly seen as a modifiable risk factor in prostate cancer.

Recent studies have shown that ultralow-carbohydrate diets, weight loss diets, supplementation with omega-3 fatty acids, pro- and anti-inflammatory diets, fasting, and even tea drinking may affect prostate cancer risk or risk for progression.

In October, a cohort study involving about 900 men under active surveillance for early stage prostate cancers found that those who reported eating a diet that adhered closely to the US government’s recommendations as indicated by the Healthy Eating Index (HEI) saw a lower risk for progression at a median 6.5 months follow-up.

These findings follow results from an observational study, published in May, that followed about 2000 men with locally advanced prostate tumors. Men consuming a primarily plant-based diet (one closely adhering to the plant-based diet index) had less likelihood of progression over a median 6.5 years than those consuming diets low in plant-based foods.

“There is an increasing body of literature that says your diet matters,” said urologist Stephen J. Freedland, MD, of Cedars-Sinai Medical Center in Los Angeles, California, and director of its Center for Integrated Research in Cancer and Lifestyle. “At the same time, there are a lot of things that could explain these associations. People who can afford lots of plant-based foods tend to have higher socioeconomic status, for example.”

What’s needed, Freedland said, are more randomized trials to test the hypotheses emerging from the longitudinal cohort studies. “That’s where I’m going with my own research,” he said. “I’d like to look at a study like [one of these] and design a trial. Let’s say we get half of patients to eat according to the healthy eating index, while half eat whatever they want. Can dietary modification change which genes are turned on and off in a tumor, as a start?”

 

Oncologist and Nutritionist Collaborate on Multiple Studies

Nutritionist Pao-Hwa Lin, PhD, of Duke University in Durham, North Carolina, has been working for several years with Freedland on trials of nutrition interventions. A longtime researcher of chronic disease and diet, she first collaborated with Freedland on a study, published in 2019, that looked at whether insulin could be driven down with diet and exercise in men treated with androgen deprivation therapy.

Not only are high levels of insulin a known contributor to prostate cancer growth, Lin said, but “insulin resistance is a very common side effect of hormone therapy. And we saw that the low carb diet was very helpful for that.” The finding led Freedland and Lin to design further trials investigating carbohydrate restriction in people with prostate cancer.

Lin said randomized trials tend to be smaller and shorter in duration than the observational cohort studies because “interventions like these can be hard to maintain, and recruitment can be hard to sustain. A very well controlled and intensive nutrition intervention is not going to be super long.” Short trial durations also mean that prostate cancer progression can be difficult to capture. Risk for progression has to be measured using surrogate markers, such as the doubling time for prostate-specific antigen (PSA).

In 2020, Freedland and Lin published results from a pilot study of 57 men who had been treated with surgery or radiation for localized prostate cancer but had a PSA recurrence and were randomized to an ultralow-carbohydrate diet or no restrictions for 6 months. The investigators saw that PSA doubling times, an intermediate measure of tumor growth rate, were slower among those consuming the low-carb diet.

Currently they are wrapping up a trial that randomizes men who have been scheduled for radical prostatectomy to daily supplementation with walnuts, a natural source of polyphenols and omega-3 acids. This time, the aim is to determine whether gene expression in tumors changes in response to supplementation.

The researchers are also recruiting for a study in men being treated for metastatic prostate cancer. This study randomizes patients to a fasting-mimicking diet, which is a type of intermittent fasting, or no dietary restrictions for 6 months.

Developed by biologist Valter Longo, PhD, of the University of Southern California, Los Angeles, the fasting-mimicking diet has been shown to boost treatment effects in women with hormone receptor–positive breast cancer. In 2023, Longo and his colleagues published results from a small pilot study of the same diet in men with prostate cancer, reporting some positive metabolic findings.

Longo, who is consulting on Lin and Freedland’s trial, “has proven that the diet is helpful in treatment outcomes for breast cancer. So we connected and decided to test it and see if it’s helpful in prostate cancer as well.”

 

More Than One Approach Likely to Work

Though Lin and Freedland have focused most of their investigations on carbohydrate restriction, neither dismisses the potential for other dietary approaches to show benefit.

“There are two main schools of thought in terms of the relationship between diet and prostate cancer,” Lin said. “One is the insulin angle, and that’s what we hypothesized when we first tested the low-carb diet. The other is the inflammation angle.”

Studies have shown greater adherence to the HEI — a diet quality indicator that favors grains, fruits, dairy, vegetables, beans, and seafood — or the plant-based diet index to be associated with lower biomarkers of inflammation, she noted.

Insulin resistance, Lin explained, “is also highly related to inflammation.” (Several of the diets being investigated in prostate cancer were originally studied in diabetes.)

Moreover, weight loss caused by low-carb diets — or other healthy diets — can have a positive effect on insulin resistance independent of diet composition. “So it is a very complicated picture — and that doesn’t exclude other pathways that could also be contributing,” she said.

On the surface, a low-carb diet that is heavy in eggs, cheeses, and meats would seem to have little in common with the HEI or a plant-based diet. But Freedland noted that there are commonalities among the approaches being studied. “No one’s promoting eating a lot of simple sugars. No one’s saying eat a lot of processed foods. All of these diets emphasize whole, natural foods,” he said.

Lin hopes that she and Freedland will one day be able to test a diet that is both lower carb and anti-inflammatory in men with prostate cancer. “Why not combine the approaches, have all the good features together?” she asked.

But Freeland pointed out and explained why most clinicians don’t make dietary recommendations to their newly diagnosed patients.

“A new prostate cancer patient already gets easily an hour discussion of treatment options, of pros and cons. Patients often become overwhelmed. And then to extend it further to talk about diet, they’ll end up even more overwhelmed.” Moreover, he said, current evidence offers doctors few take-home messages to deliver besides avoiding sugar and processed foods.

Multiple dietary approaches are likely to prove helpful in prostate cancer, and when the evidence for them is better established, patients and their doctors will want to consider lifestyle factors in choosing one. The best diet will depend on a patient’s philosophy, tastes, and willingness to follow it, he concluded.

“At the end of the day I’m not rooting for one diet or another. I just want to get the answers.”

Lin disclosed no financial conflicts of interest. Freedland disclosed serving as a speaker for AstraZeneca, Astellas, and Pfizer and as a consultant for Astellas, AstraZeneca, Bayer, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi-Aventis, and Sumitomo.

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

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Diet is increasingly seen as a modifiable risk factor in prostate cancer.

Recent studies have shown that ultralow-carbohydrate diets, weight loss diets, supplementation with omega-3 fatty acids, pro- and anti-inflammatory diets, fasting, and even tea drinking may affect prostate cancer risk or risk for progression.

In October, a cohort study involving about 900 men under active surveillance for early stage prostate cancers found that those who reported eating a diet that adhered closely to the US government’s recommendations as indicated by the Healthy Eating Index (HEI) saw a lower risk for progression at a median 6.5 months follow-up.

These findings follow results from an observational study, published in May, that followed about 2000 men with locally advanced prostate tumors. Men consuming a primarily plant-based diet (one closely adhering to the plant-based diet index) had less likelihood of progression over a median 6.5 years than those consuming diets low in plant-based foods.

“There is an increasing body of literature that says your diet matters,” said urologist Stephen J. Freedland, MD, of Cedars-Sinai Medical Center in Los Angeles, California, and director of its Center for Integrated Research in Cancer and Lifestyle. “At the same time, there are a lot of things that could explain these associations. People who can afford lots of plant-based foods tend to have higher socioeconomic status, for example.”

What’s needed, Freedland said, are more randomized trials to test the hypotheses emerging from the longitudinal cohort studies. “That’s where I’m going with my own research,” he said. “I’d like to look at a study like [one of these] and design a trial. Let’s say we get half of patients to eat according to the healthy eating index, while half eat whatever they want. Can dietary modification change which genes are turned on and off in a tumor, as a start?”

 

Oncologist and Nutritionist Collaborate on Multiple Studies

Nutritionist Pao-Hwa Lin, PhD, of Duke University in Durham, North Carolina, has been working for several years with Freedland on trials of nutrition interventions. A longtime researcher of chronic disease and diet, she first collaborated with Freedland on a study, published in 2019, that looked at whether insulin could be driven down with diet and exercise in men treated with androgen deprivation therapy.

Not only are high levels of insulin a known contributor to prostate cancer growth, Lin said, but “insulin resistance is a very common side effect of hormone therapy. And we saw that the low carb diet was very helpful for that.” The finding led Freedland and Lin to design further trials investigating carbohydrate restriction in people with prostate cancer.

Lin said randomized trials tend to be smaller and shorter in duration than the observational cohort studies because “interventions like these can be hard to maintain, and recruitment can be hard to sustain. A very well controlled and intensive nutrition intervention is not going to be super long.” Short trial durations also mean that prostate cancer progression can be difficult to capture. Risk for progression has to be measured using surrogate markers, such as the doubling time for prostate-specific antigen (PSA).

In 2020, Freedland and Lin published results from a pilot study of 57 men who had been treated with surgery or radiation for localized prostate cancer but had a PSA recurrence and were randomized to an ultralow-carbohydrate diet or no restrictions for 6 months. The investigators saw that PSA doubling times, an intermediate measure of tumor growth rate, were slower among those consuming the low-carb diet.

Currently they are wrapping up a trial that randomizes men who have been scheduled for radical prostatectomy to daily supplementation with walnuts, a natural source of polyphenols and omega-3 acids. This time, the aim is to determine whether gene expression in tumors changes in response to supplementation.

The researchers are also recruiting for a study in men being treated for metastatic prostate cancer. This study randomizes patients to a fasting-mimicking diet, which is a type of intermittent fasting, or no dietary restrictions for 6 months.

Developed by biologist Valter Longo, PhD, of the University of Southern California, Los Angeles, the fasting-mimicking diet has been shown to boost treatment effects in women with hormone receptor–positive breast cancer. In 2023, Longo and his colleagues published results from a small pilot study of the same diet in men with prostate cancer, reporting some positive metabolic findings.

Longo, who is consulting on Lin and Freedland’s trial, “has proven that the diet is helpful in treatment outcomes for breast cancer. So we connected and decided to test it and see if it’s helpful in prostate cancer as well.”

 

More Than One Approach Likely to Work

Though Lin and Freedland have focused most of their investigations on carbohydrate restriction, neither dismisses the potential for other dietary approaches to show benefit.

“There are two main schools of thought in terms of the relationship between diet and prostate cancer,” Lin said. “One is the insulin angle, and that’s what we hypothesized when we first tested the low-carb diet. The other is the inflammation angle.”

Studies have shown greater adherence to the HEI — a diet quality indicator that favors grains, fruits, dairy, vegetables, beans, and seafood — or the plant-based diet index to be associated with lower biomarkers of inflammation, she noted.

Insulin resistance, Lin explained, “is also highly related to inflammation.” (Several of the diets being investigated in prostate cancer were originally studied in diabetes.)

Moreover, weight loss caused by low-carb diets — or other healthy diets — can have a positive effect on insulin resistance independent of diet composition. “So it is a very complicated picture — and that doesn’t exclude other pathways that could also be contributing,” she said.

On the surface, a low-carb diet that is heavy in eggs, cheeses, and meats would seem to have little in common with the HEI or a plant-based diet. But Freedland noted that there are commonalities among the approaches being studied. “No one’s promoting eating a lot of simple sugars. No one’s saying eat a lot of processed foods. All of these diets emphasize whole, natural foods,” he said.

Lin hopes that she and Freedland will one day be able to test a diet that is both lower carb and anti-inflammatory in men with prostate cancer. “Why not combine the approaches, have all the good features together?” she asked.

But Freeland pointed out and explained why most clinicians don’t make dietary recommendations to their newly diagnosed patients.

“A new prostate cancer patient already gets easily an hour discussion of treatment options, of pros and cons. Patients often become overwhelmed. And then to extend it further to talk about diet, they’ll end up even more overwhelmed.” Moreover, he said, current evidence offers doctors few take-home messages to deliver besides avoiding sugar and processed foods.

Multiple dietary approaches are likely to prove helpful in prostate cancer, and when the evidence for them is better established, patients and their doctors will want to consider lifestyle factors in choosing one. The best diet will depend on a patient’s philosophy, tastes, and willingness to follow it, he concluded.

“At the end of the day I’m not rooting for one diet or another. I just want to get the answers.”

Lin disclosed no financial conflicts of interest. Freedland disclosed serving as a speaker for AstraZeneca, Astellas, and Pfizer and as a consultant for Astellas, AstraZeneca, Bayer, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi-Aventis, and Sumitomo.

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

Diet is increasingly seen as a modifiable risk factor in prostate cancer.

Recent studies have shown that ultralow-carbohydrate diets, weight loss diets, supplementation with omega-3 fatty acids, pro- and anti-inflammatory diets, fasting, and even tea drinking may affect prostate cancer risk or risk for progression.

In October, a cohort study involving about 900 men under active surveillance for early stage prostate cancers found that those who reported eating a diet that adhered closely to the US government’s recommendations as indicated by the Healthy Eating Index (HEI) saw a lower risk for progression at a median 6.5 months follow-up.

These findings follow results from an observational study, published in May, that followed about 2000 men with locally advanced prostate tumors. Men consuming a primarily plant-based diet (one closely adhering to the plant-based diet index) had less likelihood of progression over a median 6.5 years than those consuming diets low in plant-based foods.

“There is an increasing body of literature that says your diet matters,” said urologist Stephen J. Freedland, MD, of Cedars-Sinai Medical Center in Los Angeles, California, and director of its Center for Integrated Research in Cancer and Lifestyle. “At the same time, there are a lot of things that could explain these associations. People who can afford lots of plant-based foods tend to have higher socioeconomic status, for example.”

What’s needed, Freedland said, are more randomized trials to test the hypotheses emerging from the longitudinal cohort studies. “That’s where I’m going with my own research,” he said. “I’d like to look at a study like [one of these] and design a trial. Let’s say we get half of patients to eat according to the healthy eating index, while half eat whatever they want. Can dietary modification change which genes are turned on and off in a tumor, as a start?”

 

Oncologist and Nutritionist Collaborate on Multiple Studies

Nutritionist Pao-Hwa Lin, PhD, of Duke University in Durham, North Carolina, has been working for several years with Freedland on trials of nutrition interventions. A longtime researcher of chronic disease and diet, she first collaborated with Freedland on a study, published in 2019, that looked at whether insulin could be driven down with diet and exercise in men treated with androgen deprivation therapy.

Not only are high levels of insulin a known contributor to prostate cancer growth, Lin said, but “insulin resistance is a very common side effect of hormone therapy. And we saw that the low carb diet was very helpful for that.” The finding led Freedland and Lin to design further trials investigating carbohydrate restriction in people with prostate cancer.

Lin said randomized trials tend to be smaller and shorter in duration than the observational cohort studies because “interventions like these can be hard to maintain, and recruitment can be hard to sustain. A very well controlled and intensive nutrition intervention is not going to be super long.” Short trial durations also mean that prostate cancer progression can be difficult to capture. Risk for progression has to be measured using surrogate markers, such as the doubling time for prostate-specific antigen (PSA).

In 2020, Freedland and Lin published results from a pilot study of 57 men who had been treated with surgery or radiation for localized prostate cancer but had a PSA recurrence and were randomized to an ultralow-carbohydrate diet or no restrictions for 6 months. The investigators saw that PSA doubling times, an intermediate measure of tumor growth rate, were slower among those consuming the low-carb diet.

Currently they are wrapping up a trial that randomizes men who have been scheduled for radical prostatectomy to daily supplementation with walnuts, a natural source of polyphenols and omega-3 acids. This time, the aim is to determine whether gene expression in tumors changes in response to supplementation.

The researchers are also recruiting for a study in men being treated for metastatic prostate cancer. This study randomizes patients to a fasting-mimicking diet, which is a type of intermittent fasting, or no dietary restrictions for 6 months.

Developed by biologist Valter Longo, PhD, of the University of Southern California, Los Angeles, the fasting-mimicking diet has been shown to boost treatment effects in women with hormone receptor–positive breast cancer. In 2023, Longo and his colleagues published results from a small pilot study of the same diet in men with prostate cancer, reporting some positive metabolic findings.

Longo, who is consulting on Lin and Freedland’s trial, “has proven that the diet is helpful in treatment outcomes for breast cancer. So we connected and decided to test it and see if it’s helpful in prostate cancer as well.”

 

More Than One Approach Likely to Work

Though Lin and Freedland have focused most of their investigations on carbohydrate restriction, neither dismisses the potential for other dietary approaches to show benefit.

“There are two main schools of thought in terms of the relationship between diet and prostate cancer,” Lin said. “One is the insulin angle, and that’s what we hypothesized when we first tested the low-carb diet. The other is the inflammation angle.”

Studies have shown greater adherence to the HEI — a diet quality indicator that favors grains, fruits, dairy, vegetables, beans, and seafood — or the plant-based diet index to be associated with lower biomarkers of inflammation, she noted.

Insulin resistance, Lin explained, “is also highly related to inflammation.” (Several of the diets being investigated in prostate cancer were originally studied in diabetes.)

Moreover, weight loss caused by low-carb diets — or other healthy diets — can have a positive effect on insulin resistance independent of diet composition. “So it is a very complicated picture — and that doesn’t exclude other pathways that could also be contributing,” she said.

On the surface, a low-carb diet that is heavy in eggs, cheeses, and meats would seem to have little in common with the HEI or a plant-based diet. But Freedland noted that there are commonalities among the approaches being studied. “No one’s promoting eating a lot of simple sugars. No one’s saying eat a lot of processed foods. All of these diets emphasize whole, natural foods,” he said.

Lin hopes that she and Freedland will one day be able to test a diet that is both lower carb and anti-inflammatory in men with prostate cancer. “Why not combine the approaches, have all the good features together?” she asked.

But Freeland pointed out and explained why most clinicians don’t make dietary recommendations to their newly diagnosed patients.

“A new prostate cancer patient already gets easily an hour discussion of treatment options, of pros and cons. Patients often become overwhelmed. And then to extend it further to talk about diet, they’ll end up even more overwhelmed.” Moreover, he said, current evidence offers doctors few take-home messages to deliver besides avoiding sugar and processed foods.

Multiple dietary approaches are likely to prove helpful in prostate cancer, and when the evidence for them is better established, patients and their doctors will want to consider lifestyle factors in choosing one. The best diet will depend on a patient’s philosophy, tastes, and willingness to follow it, he concluded.

“At the end of the day I’m not rooting for one diet or another. I just want to get the answers.”

Lin disclosed no financial conflicts of interest. Freedland disclosed serving as a speaker for AstraZeneca, Astellas, and Pfizer and as a consultant for Astellas, AstraZeneca, Bayer, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi-Aventis, and Sumitomo.

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

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Low-Dose Oral Minoxidil: Expert Consensus Provide Guidance for Treating Hair Loss

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Recently published consensus guidelines for low-dose oral minoxidil (LDOM) treatment of hair loss provide best-practice recommendations in areas ranging from pretreatment considerations and counseling to patient monitoring. With large randomized, controlled trials lacking, the guidelines authors and other dermatologists said the paper provides practical pointers that should increase clinicians’ confidence in prescribing LDOM for hair loss.

Comfort and Confidence

Benjamin N. Ungar, MD, director of the Alopecia Center of Excellence at Mount Sinai Icahn School of Medicine, New York City, said he hopes that the guidelines will “make dermatologists in practice more comfortable with the use of low-dose oral minoxidil to treat different kinds of hair loss, and therefore, more patients will benefit.” He was not an author of the paper, which was published online in JAMA Dermatology on November 20, but was asked to comment.

Dr. Benjamin N. Ungar



Members of the multidisciplinary Low-Dose Oral Minoxidil Initiation steering committee recruited dermatologists with hair loss expertise from 12 countries. Using a modified four-round Delphi process that required at least 70% agreement, the group of 43 dermatologists crafted 76 consensus statements. “Notably,” said Co-senior author Jennifer Fu, MD, director of the Hair Disorders Clinic at the University of California, San Francisco, “27 items achieved at least 90% consensus after the first two rounds, indicating broad agreement in expert practice.”

Dr. Jennifer Fu



 

Indications for LDOM

At least 90% of experts concurred regarding the appropriateness of LDOM use for androgenetic alopecia (AGA) and age-related thinning and in cases where topical minoxidil proves ineffective or problematic. Additional situations in which LDOM might provide direct benefit involve follicular miniaturization, such as alopecia areata, or hair cycle disruption, such as chemotherapy. The authors also recommended considering LDOM over topical minoxidil when the latter is more expensive and when patients desire enhanced hypertrichosis.

 

Contraindications and Precautions

Before prescribing LDOM, the authors wrote, clinicians may consult with primary care or cardiology when contraindications (cardiovascular issues, pregnancy/nursing, and potential drug interactions) or precautions (history of tachycardia or arrhythmia, hypotension, or impaired kidney function) exist. Patients with precautions may require blood pressure monitoring, as well as monitoring for adverse effects of treatment. The panel also suggested the latter for all patients at the time of LDOM initiation and dose escalation. The authors advised against routine baseline laboratory and EKG testing in cases without relevant precautions.



 

Dosing Considerations

Along with systemic adverse event risk and baseline hair loss severity, key dosing considerations include patient age, sex, and whether patients desire hypertrichosis. Consensus on daily doses for adolescent females and males begins at 0.625 mg and 1.25 mg, respectively, and ranges up to 2.5 mg for adolescent females vs 5 mg for adult females and adolescent and adult males.

Presently, said Ungar, many dermatologists — including some who prescribe LDOM — remain uncomfortable even with very low doses, perhaps because of an invalid perception of cardiovascular safety issues including potential hypotension and pericardial effusions. However, recently published data include a review published November 7 in the Journal of the American Academy of Dermatology, which showed no significant effect of LDOM on blood pressure. And in a September Journal of Drugs in Dermatology article the authors found no impact on pericardial effusions in a 100-patient cohort.

Some dermatologists worry about the impact hypertrichosis may have on patients, Ungar added. Although incidence estimates range from 15% to 30%, he said, more than half of his patients experience hypertrichosis. “However, most continue treatment because the beneficial effects outweigh the effect of hypertrichosis.”



 

Practical Roadmap

Adam Friedman, MD, who was not involved with the publication, applauds its inclusion of pragmatic clinical guidance, which he said consensus papers often lack. “This paper sets a great roadmap for working low-dose oral minoxidil into your clinical practice, Friedman, professor and chair of dermatology at George Washington University, Washington, DC, said in an interview.

Dr. Adam Friedman



Rather than limiting LDOM use to AGA, he said, the paper is most helpful in showing the spectrum of disease states for which the expert panel prescribes LDOM. “We use it as adjunctive therapy for many other things, both scarring and nonscarring hair loss,” he added.

In appropriate clinical contexts, the authors wrote, clinicians may consider combining LDOM with spironolactone or beta-blockers. Friedman said that in his hands, combining LDOM with a 5-alpha reductase inhibitor (5ARI) is “absolutely outstanding.” Minoxidil increases blood flow to the scalp, he explained, while 5ARIs prevent production of dihydrotestosterone, which miniaturizes hair.

Fu said, “We hope these consensus outcomes will be helpful to dermatology colleagues as they consider using LDOM to treat hair loss in their adult and adolescent patient populations. We anticipate that these guidelines will be updated as additional evidence-based data emerges and are encouraged that we are already seeing new publications on this topic.”

Important areas for future research, she noted, include pediatric use of LDOM, the comparative efficacy of topical vs oral minoxidil, the safety of oral minoxidil for patients with a history of allergic contact dermatitis to topical minoxidil, and the use of other off-label forms of minoxidil, such as compounded oral minoxidil and sublingual minoxidil.

The study was funded by the University of California, San Francisco, Department of Dermatology Medical Student Summer Research Fellowship Program. Fu reported personal fees from Pfizer, Eli Lilly and Company, and Sun Pharma outside of the study. The full list of author disclosures can be found in the paper. Ungar and Friedman reported no relevant financial relationships.

 

A version of this article appeared on Medscape.com.

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Recently published consensus guidelines for low-dose oral minoxidil (LDOM) treatment of hair loss provide best-practice recommendations in areas ranging from pretreatment considerations and counseling to patient monitoring. With large randomized, controlled trials lacking, the guidelines authors and other dermatologists said the paper provides practical pointers that should increase clinicians’ confidence in prescribing LDOM for hair loss.

Comfort and Confidence

Benjamin N. Ungar, MD, director of the Alopecia Center of Excellence at Mount Sinai Icahn School of Medicine, New York City, said he hopes that the guidelines will “make dermatologists in practice more comfortable with the use of low-dose oral minoxidil to treat different kinds of hair loss, and therefore, more patients will benefit.” He was not an author of the paper, which was published online in JAMA Dermatology on November 20, but was asked to comment.

Dr. Benjamin N. Ungar



Members of the multidisciplinary Low-Dose Oral Minoxidil Initiation steering committee recruited dermatologists with hair loss expertise from 12 countries. Using a modified four-round Delphi process that required at least 70% agreement, the group of 43 dermatologists crafted 76 consensus statements. “Notably,” said Co-senior author Jennifer Fu, MD, director of the Hair Disorders Clinic at the University of California, San Francisco, “27 items achieved at least 90% consensus after the first two rounds, indicating broad agreement in expert practice.”

Dr. Jennifer Fu



 

Indications for LDOM

At least 90% of experts concurred regarding the appropriateness of LDOM use for androgenetic alopecia (AGA) and age-related thinning and in cases where topical minoxidil proves ineffective or problematic. Additional situations in which LDOM might provide direct benefit involve follicular miniaturization, such as alopecia areata, or hair cycle disruption, such as chemotherapy. The authors also recommended considering LDOM over topical minoxidil when the latter is more expensive and when patients desire enhanced hypertrichosis.

 

Contraindications and Precautions

Before prescribing LDOM, the authors wrote, clinicians may consult with primary care or cardiology when contraindications (cardiovascular issues, pregnancy/nursing, and potential drug interactions) or precautions (history of tachycardia or arrhythmia, hypotension, or impaired kidney function) exist. Patients with precautions may require blood pressure monitoring, as well as monitoring for adverse effects of treatment. The panel also suggested the latter for all patients at the time of LDOM initiation and dose escalation. The authors advised against routine baseline laboratory and EKG testing in cases without relevant precautions.



 

Dosing Considerations

Along with systemic adverse event risk and baseline hair loss severity, key dosing considerations include patient age, sex, and whether patients desire hypertrichosis. Consensus on daily doses for adolescent females and males begins at 0.625 mg and 1.25 mg, respectively, and ranges up to 2.5 mg for adolescent females vs 5 mg for adult females and adolescent and adult males.

Presently, said Ungar, many dermatologists — including some who prescribe LDOM — remain uncomfortable even with very low doses, perhaps because of an invalid perception of cardiovascular safety issues including potential hypotension and pericardial effusions. However, recently published data include a review published November 7 in the Journal of the American Academy of Dermatology, which showed no significant effect of LDOM on blood pressure. And in a September Journal of Drugs in Dermatology article the authors found no impact on pericardial effusions in a 100-patient cohort.

Some dermatologists worry about the impact hypertrichosis may have on patients, Ungar added. Although incidence estimates range from 15% to 30%, he said, more than half of his patients experience hypertrichosis. “However, most continue treatment because the beneficial effects outweigh the effect of hypertrichosis.”



 

Practical Roadmap

Adam Friedman, MD, who was not involved with the publication, applauds its inclusion of pragmatic clinical guidance, which he said consensus papers often lack. “This paper sets a great roadmap for working low-dose oral minoxidil into your clinical practice, Friedman, professor and chair of dermatology at George Washington University, Washington, DC, said in an interview.

Dr. Adam Friedman



Rather than limiting LDOM use to AGA, he said, the paper is most helpful in showing the spectrum of disease states for which the expert panel prescribes LDOM. “We use it as adjunctive therapy for many other things, both scarring and nonscarring hair loss,” he added.

In appropriate clinical contexts, the authors wrote, clinicians may consider combining LDOM with spironolactone or beta-blockers. Friedman said that in his hands, combining LDOM with a 5-alpha reductase inhibitor (5ARI) is “absolutely outstanding.” Minoxidil increases blood flow to the scalp, he explained, while 5ARIs prevent production of dihydrotestosterone, which miniaturizes hair.

Fu said, “We hope these consensus outcomes will be helpful to dermatology colleagues as they consider using LDOM to treat hair loss in their adult and adolescent patient populations. We anticipate that these guidelines will be updated as additional evidence-based data emerges and are encouraged that we are already seeing new publications on this topic.”

Important areas for future research, she noted, include pediatric use of LDOM, the comparative efficacy of topical vs oral minoxidil, the safety of oral minoxidil for patients with a history of allergic contact dermatitis to topical minoxidil, and the use of other off-label forms of minoxidil, such as compounded oral minoxidil and sublingual minoxidil.

The study was funded by the University of California, San Francisco, Department of Dermatology Medical Student Summer Research Fellowship Program. Fu reported personal fees from Pfizer, Eli Lilly and Company, and Sun Pharma outside of the study. The full list of author disclosures can be found in the paper. Ungar and Friedman reported no relevant financial relationships.

 

A version of this article appeared on Medscape.com.

Recently published consensus guidelines for low-dose oral minoxidil (LDOM) treatment of hair loss provide best-practice recommendations in areas ranging from pretreatment considerations and counseling to patient monitoring. With large randomized, controlled trials lacking, the guidelines authors and other dermatologists said the paper provides practical pointers that should increase clinicians’ confidence in prescribing LDOM for hair loss.

Comfort and Confidence

Benjamin N. Ungar, MD, director of the Alopecia Center of Excellence at Mount Sinai Icahn School of Medicine, New York City, said he hopes that the guidelines will “make dermatologists in practice more comfortable with the use of low-dose oral minoxidil to treat different kinds of hair loss, and therefore, more patients will benefit.” He was not an author of the paper, which was published online in JAMA Dermatology on November 20, but was asked to comment.

Dr. Benjamin N. Ungar



Members of the multidisciplinary Low-Dose Oral Minoxidil Initiation steering committee recruited dermatologists with hair loss expertise from 12 countries. Using a modified four-round Delphi process that required at least 70% agreement, the group of 43 dermatologists crafted 76 consensus statements. “Notably,” said Co-senior author Jennifer Fu, MD, director of the Hair Disorders Clinic at the University of California, San Francisco, “27 items achieved at least 90% consensus after the first two rounds, indicating broad agreement in expert practice.”

Dr. Jennifer Fu



 

Indications for LDOM

At least 90% of experts concurred regarding the appropriateness of LDOM use for androgenetic alopecia (AGA) and age-related thinning and in cases where topical minoxidil proves ineffective or problematic. Additional situations in which LDOM might provide direct benefit involve follicular miniaturization, such as alopecia areata, or hair cycle disruption, such as chemotherapy. The authors also recommended considering LDOM over topical minoxidil when the latter is more expensive and when patients desire enhanced hypertrichosis.

 

Contraindications and Precautions

Before prescribing LDOM, the authors wrote, clinicians may consult with primary care or cardiology when contraindications (cardiovascular issues, pregnancy/nursing, and potential drug interactions) or precautions (history of tachycardia or arrhythmia, hypotension, or impaired kidney function) exist. Patients with precautions may require blood pressure monitoring, as well as monitoring for adverse effects of treatment. The panel also suggested the latter for all patients at the time of LDOM initiation and dose escalation. The authors advised against routine baseline laboratory and EKG testing in cases without relevant precautions.



 

Dosing Considerations

Along with systemic adverse event risk and baseline hair loss severity, key dosing considerations include patient age, sex, and whether patients desire hypertrichosis. Consensus on daily doses for adolescent females and males begins at 0.625 mg and 1.25 mg, respectively, and ranges up to 2.5 mg for adolescent females vs 5 mg for adult females and adolescent and adult males.

Presently, said Ungar, many dermatologists — including some who prescribe LDOM — remain uncomfortable even with very low doses, perhaps because of an invalid perception of cardiovascular safety issues including potential hypotension and pericardial effusions. However, recently published data include a review published November 7 in the Journal of the American Academy of Dermatology, which showed no significant effect of LDOM on blood pressure. And in a September Journal of Drugs in Dermatology article the authors found no impact on pericardial effusions in a 100-patient cohort.

Some dermatologists worry about the impact hypertrichosis may have on patients, Ungar added. Although incidence estimates range from 15% to 30%, he said, more than half of his patients experience hypertrichosis. “However, most continue treatment because the beneficial effects outweigh the effect of hypertrichosis.”



 

Practical Roadmap

Adam Friedman, MD, who was not involved with the publication, applauds its inclusion of pragmatic clinical guidance, which he said consensus papers often lack. “This paper sets a great roadmap for working low-dose oral minoxidil into your clinical practice, Friedman, professor and chair of dermatology at George Washington University, Washington, DC, said in an interview.

Dr. Adam Friedman



Rather than limiting LDOM use to AGA, he said, the paper is most helpful in showing the spectrum of disease states for which the expert panel prescribes LDOM. “We use it as adjunctive therapy for many other things, both scarring and nonscarring hair loss,” he added.

In appropriate clinical contexts, the authors wrote, clinicians may consider combining LDOM with spironolactone or beta-blockers. Friedman said that in his hands, combining LDOM with a 5-alpha reductase inhibitor (5ARI) is “absolutely outstanding.” Minoxidil increases blood flow to the scalp, he explained, while 5ARIs prevent production of dihydrotestosterone, which miniaturizes hair.

Fu said, “We hope these consensus outcomes will be helpful to dermatology colleagues as they consider using LDOM to treat hair loss in their adult and adolescent patient populations. We anticipate that these guidelines will be updated as additional evidence-based data emerges and are encouraged that we are already seeing new publications on this topic.”

Important areas for future research, she noted, include pediatric use of LDOM, the comparative efficacy of topical vs oral minoxidil, the safety of oral minoxidil for patients with a history of allergic contact dermatitis to topical minoxidil, and the use of other off-label forms of minoxidil, such as compounded oral minoxidil and sublingual minoxidil.

The study was funded by the University of California, San Francisco, Department of Dermatology Medical Student Summer Research Fellowship Program. Fu reported personal fees from Pfizer, Eli Lilly and Company, and Sun Pharma outside of the study. The full list of author disclosures can be found in the paper. Ungar and Friedman reported no relevant financial relationships.

 

A version of this article appeared on Medscape.com.

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NCCN Expands Cancer Genetic Risk Assessment Guidelines

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The National Comprehensive Cancer Network (NCCN) has expanded two cancer genetic risk assessment guidelines to meet the growing understanding of hereditary cancer risk and use of genetic tests in cancer prevention, screening, and treatment. 

Additional cancer types were included in the title and content for both guidelines. Prostate cancer was added to Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate, and endometrial and gastric cancer were added to Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric.

For these cancers, the expanded guidelines include information on when genetic testing is recommended and what type of testing may be best. These guidelines also detail the hereditary conditions and genetic mutations associated with elevated cancer risk and include appropriate “next steps” for individuals who have them, which may involve increased screening or prevention surgeries.

“These updates include the spectrum of genes associated with genetic syndromes, the range of risk associated with each pathogenic variant, the improvements in screening and prevention strategies, the role of genetic data to inform cancer treatment, and the expansion of the role of genetic counseling as this field moves forward,” Mary B. Daly, MD, PhD, with Fox Chase Cancer Center, Philadelphia, Pennsylvania, said in a news release. Daly chaired the panel that updated the breast, ovarian, pancreatic, and prostate cancer guidelines.

Oncologists should, for instance, ask patients about their family and personal history of cancer and known germline variants at time of initial diagnosis. With prostate cancer, if patients meet criteria for germline testing, multigene testing should include a host of variants, including BRCA1, BRCA2, ATM, PALB2, CHEK2, HOXB13, MLH1, MSH2, MSH6, and PMS2.

The updated guidelines on genetic risk assessment of colorectal, endometrial, and gastric cancer include new recommendations to consider for hereditary cancer screening in patients with newly diagnosed endometrial cancer, for evaluating and managing CDH1-associated gastric cancer risk, and for managing gastric cancer risk in patients with APC pathogenic variants. 

For CDH1-associated gastric cancer, for instance, the guidelines recommend carriers be referred to institutions with expertise in managing risks for cancer associated with CDH1, “given the still limited understanding and rarity of this syndrome.” 

“These expanded guidelines reflect the recommendations from leading experts on genetic testing based on the latest scientific research across the cancer spectrum, consolidated into two convenient resources,” said NCCN CEO Crystal S. Denlinger, MD, with Fox Chase Cancer Center, in a news release

“This information is critical for guiding shared decision-making between health care providers and their patients, enhancing screening practices as appropriate, and potentially choosing options for prevention and targeted treatment choices. Genetic testing guidelines enable us to better care for people with cancer and their family members,” Denlinger added.

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

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The National Comprehensive Cancer Network (NCCN) has expanded two cancer genetic risk assessment guidelines to meet the growing understanding of hereditary cancer risk and use of genetic tests in cancer prevention, screening, and treatment. 

Additional cancer types were included in the title and content for both guidelines. Prostate cancer was added to Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate, and endometrial and gastric cancer were added to Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric.

For these cancers, the expanded guidelines include information on when genetic testing is recommended and what type of testing may be best. These guidelines also detail the hereditary conditions and genetic mutations associated with elevated cancer risk and include appropriate “next steps” for individuals who have them, which may involve increased screening or prevention surgeries.

“These updates include the spectrum of genes associated with genetic syndromes, the range of risk associated with each pathogenic variant, the improvements in screening and prevention strategies, the role of genetic data to inform cancer treatment, and the expansion of the role of genetic counseling as this field moves forward,” Mary B. Daly, MD, PhD, with Fox Chase Cancer Center, Philadelphia, Pennsylvania, said in a news release. Daly chaired the panel that updated the breast, ovarian, pancreatic, and prostate cancer guidelines.

Oncologists should, for instance, ask patients about their family and personal history of cancer and known germline variants at time of initial diagnosis. With prostate cancer, if patients meet criteria for germline testing, multigene testing should include a host of variants, including BRCA1, BRCA2, ATM, PALB2, CHEK2, HOXB13, MLH1, MSH2, MSH6, and PMS2.

The updated guidelines on genetic risk assessment of colorectal, endometrial, and gastric cancer include new recommendations to consider for hereditary cancer screening in patients with newly diagnosed endometrial cancer, for evaluating and managing CDH1-associated gastric cancer risk, and for managing gastric cancer risk in patients with APC pathogenic variants. 

For CDH1-associated gastric cancer, for instance, the guidelines recommend carriers be referred to institutions with expertise in managing risks for cancer associated with CDH1, “given the still limited understanding and rarity of this syndrome.” 

“These expanded guidelines reflect the recommendations from leading experts on genetic testing based on the latest scientific research across the cancer spectrum, consolidated into two convenient resources,” said NCCN CEO Crystal S. Denlinger, MD, with Fox Chase Cancer Center, in a news release

“This information is critical for guiding shared decision-making between health care providers and their patients, enhancing screening practices as appropriate, and potentially choosing options for prevention and targeted treatment choices. Genetic testing guidelines enable us to better care for people with cancer and their family members,” Denlinger added.

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

The National Comprehensive Cancer Network (NCCN) has expanded two cancer genetic risk assessment guidelines to meet the growing understanding of hereditary cancer risk and use of genetic tests in cancer prevention, screening, and treatment. 

Additional cancer types were included in the title and content for both guidelines. Prostate cancer was added to Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate, and endometrial and gastric cancer were added to Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric.

For these cancers, the expanded guidelines include information on when genetic testing is recommended and what type of testing may be best. These guidelines also detail the hereditary conditions and genetic mutations associated with elevated cancer risk and include appropriate “next steps” for individuals who have them, which may involve increased screening or prevention surgeries.

“These updates include the spectrum of genes associated with genetic syndromes, the range of risk associated with each pathogenic variant, the improvements in screening and prevention strategies, the role of genetic data to inform cancer treatment, and the expansion of the role of genetic counseling as this field moves forward,” Mary B. Daly, MD, PhD, with Fox Chase Cancer Center, Philadelphia, Pennsylvania, said in a news release. Daly chaired the panel that updated the breast, ovarian, pancreatic, and prostate cancer guidelines.

Oncologists should, for instance, ask patients about their family and personal history of cancer and known germline variants at time of initial diagnosis. With prostate cancer, if patients meet criteria for germline testing, multigene testing should include a host of variants, including BRCA1, BRCA2, ATM, PALB2, CHEK2, HOXB13, MLH1, MSH2, MSH6, and PMS2.

The updated guidelines on genetic risk assessment of colorectal, endometrial, and gastric cancer include new recommendations to consider for hereditary cancer screening in patients with newly diagnosed endometrial cancer, for evaluating and managing CDH1-associated gastric cancer risk, and for managing gastric cancer risk in patients with APC pathogenic variants. 

For CDH1-associated gastric cancer, for instance, the guidelines recommend carriers be referred to institutions with expertise in managing risks for cancer associated with CDH1, “given the still limited understanding and rarity of this syndrome.” 

“These expanded guidelines reflect the recommendations from leading experts on genetic testing based on the latest scientific research across the cancer spectrum, consolidated into two convenient resources,” said NCCN CEO Crystal S. Denlinger, MD, with Fox Chase Cancer Center, in a news release

“This information is critical for guiding shared decision-making between health care providers and their patients, enhancing screening practices as appropriate, and potentially choosing options for prevention and targeted treatment choices. Genetic testing guidelines enable us to better care for people with cancer and their family members,” Denlinger added.

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

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Prostate Cancer: Has Active Surveillance Solved the Problem of Overtreatment?

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Overtreatment of men with prostate cancer and limited life expectancy (LE) has persisted in the era of active surveillance and worsened in some instances, according to a new study.

“Overtreatment of men with limited longevity for intermediate- and high-risk tumors has not only failed to improve but has actually worsened over the last 20 years,” Timothy Daskivich, MD, MSHPM, with Cedars-Sinai Medical Center, Los Angeles, said in an interview.

“Many doctors assume that the increase in uptake of active surveillance for low-risk prostate cancers has solved the problem of overtreatment, but this trend has not affected overtreatment of men with low likelihood of living long enough to benefit from treatment who have higher-risk tumors,” Daskivich said.

The study was published online on November 11 in JAMA Internal Medicine.

‘Concerning’ Real-World Data

For men with low- and intermediate-risk prostate cancer expected to live fewer than 10 years, prostate cancer screening and aggressive treatment are not recommended.

Daskivich and colleagues analyzed data on 243,928 men (mean age, 66 years) in the Veterans Affairs (VA) Health System with clinically localized prostate cancer diagnosed between 2000 and 2019.

About 21% had LE < 10 years, and about 4% had LE < 5 years, according to the validated age-adjusted Prostate Cancer Comorbidity Index.

Overtreatment was defined as aggressive treatment (surgery or radiation) in those with LE < 10 years and low- to intermediate-risk disease and in those with LE < 5 years and high-risk disease, in line with current guidelines.

Among men with LE < 10 years, the proportion of men overtreated with surgery or radiotherapy for low-risk disease decreased 22% but increased 22% for intermediate-risk disease during the study period.

Among men with LE < 5 years, the proportion of men treated with definitive treatment for high-risk disease increased 29%.

“While lower-risk tumors are treated less aggressively across the board, including in men with limited longevity, it seems that we are more indiscriminately treating men with higher-risk disease without considering their expected longevity,” Daskivich said in an interview.

 

Is This Happening in the General US Population?

Daskivich noted that the sample included a large sample of men diagnosed with localized prostate cancer in the VA Health System.

“Rates of overtreatment are likely to be lower in the VA [Health System], so the problem may be worse in the community setting. The VA [Health System] has been exemplary in its uptake of active surveillance for low-risk cancers, leading the effort to reduce overtreatment of men with low-risk cancers. However, the problem of overtreatment of men with limited longevity persists in the VA [Health System], underscoring the pervasiveness of this problem,” he explained.

“We don’t have a perfect head-to-head comparison of overtreatment in the VA setting vs in the community. [However, one study shows] that this is not a VA-specific phenomenon and that there is an increase in overtreatment of men with limited longevity in a Medicare population as well,” Daskivich noted.

 

Is Overtreatment All Bad?

Overtreatment of prostate cancer, especially in cases where the cancer is unlikely to progress or cause symptoms, can lead to significant physical, psychological, and financial harms, Christopher Anderson, MD, urologist with Columbia University Irving Medical Center in New York City, who wasn’t involved in the study, noted in an interview.

In the study by Daskivich and colleagues, over three quarters of the overtreatment was radiation therapy, which carries the risk for urinary, bowel, and sexual issues.

“Overscreening, which can lead to overtreatment, is a core issue,” Anderson said. It’s easy to order a “simple” prostate-specific antigen blood test, but in an older man with limited LE, that can lead to a host of further testing, he said.

Stopping the pipeline of overscreening that then feeds into the cascade of overtreatment is the first step in addressing the problem of prostate cancer overtreatment, Nancy Li Schoenborn, MD, MHS, with Johns Hopkins University School of Medicine, Baltimore, and Louise C. Walter, MD, with University of California San Francisco, wrote in an editorial in JAMA Internal Medicine.

Considering LE during screening decision-making is “fundamental to reducing harms of prostate cancer overdiagnosis and overtreatment” because limited LE increases the likelihood of experiencing “harms all along the diagnostic and treatment cascade following screening,” the editorial writers said.

The time spent diagnosing, monitoring, and treating asymptomatic prostate cancer in men with limited LE distracts from monitoring and treating chronic symptomatic life-limiting illnesses, they noted.

 

Tough to Talk About?

Anderson noted that, in general, doctors are not great at estimating and counseling patients on LE. “It’s sometimes difficult to have that conversation,” he said.

Daskivich said physicians may fail to include average LE when advising patients on treatments because they believe that the patients do not want to discuss this topic. “Yet, in interviews with patients, we found that prostate cancer patients reported they wanted this information,” he continued, in an interview.

Solving the problem of overscreening and overtreatment will require a “multifaceted approach, including improving access to life expectancy data at the point of care for providers, educating providers on how to communicate this information, and improving data sources to predict longevity,” Daskivich said.

He said it’s equally important to note that some men with prostate cancer may choose treatment even if they have a limited longevity.

“Not all patients will choose conservative management, even if it is recommended by guidelines. However, they need to be given the opportunity to make a good decision for themselves with the best possible data,” Daskivich said.

This work was supported in part by a US Department of VA Merit Review. Daskivich reported receiving personal fees from the Medical Education Speakers Network, EDAP, and RAND; research support from Lantheus and Janssen; and a patent pending for a system for healthcare visit quality assessment outside the submitted work. Schoenborn, Walter, and Anderson had no relevant disclosures.

 

A version of this article appeared on Medscape.com.

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Overtreatment of men with prostate cancer and limited life expectancy (LE) has persisted in the era of active surveillance and worsened in some instances, according to a new study.

“Overtreatment of men with limited longevity for intermediate- and high-risk tumors has not only failed to improve but has actually worsened over the last 20 years,” Timothy Daskivich, MD, MSHPM, with Cedars-Sinai Medical Center, Los Angeles, said in an interview.

“Many doctors assume that the increase in uptake of active surveillance for low-risk prostate cancers has solved the problem of overtreatment, but this trend has not affected overtreatment of men with low likelihood of living long enough to benefit from treatment who have higher-risk tumors,” Daskivich said.

The study was published online on November 11 in JAMA Internal Medicine.

‘Concerning’ Real-World Data

For men with low- and intermediate-risk prostate cancer expected to live fewer than 10 years, prostate cancer screening and aggressive treatment are not recommended.

Daskivich and colleagues analyzed data on 243,928 men (mean age, 66 years) in the Veterans Affairs (VA) Health System with clinically localized prostate cancer diagnosed between 2000 and 2019.

About 21% had LE < 10 years, and about 4% had LE < 5 years, according to the validated age-adjusted Prostate Cancer Comorbidity Index.

Overtreatment was defined as aggressive treatment (surgery or radiation) in those with LE < 10 years and low- to intermediate-risk disease and in those with LE < 5 years and high-risk disease, in line with current guidelines.

Among men with LE < 10 years, the proportion of men overtreated with surgery or radiotherapy for low-risk disease decreased 22% but increased 22% for intermediate-risk disease during the study period.

Among men with LE < 5 years, the proportion of men treated with definitive treatment for high-risk disease increased 29%.

“While lower-risk tumors are treated less aggressively across the board, including in men with limited longevity, it seems that we are more indiscriminately treating men with higher-risk disease without considering their expected longevity,” Daskivich said in an interview.

 

Is This Happening in the General US Population?

Daskivich noted that the sample included a large sample of men diagnosed with localized prostate cancer in the VA Health System.

“Rates of overtreatment are likely to be lower in the VA [Health System], so the problem may be worse in the community setting. The VA [Health System] has been exemplary in its uptake of active surveillance for low-risk cancers, leading the effort to reduce overtreatment of men with low-risk cancers. However, the problem of overtreatment of men with limited longevity persists in the VA [Health System], underscoring the pervasiveness of this problem,” he explained.

“We don’t have a perfect head-to-head comparison of overtreatment in the VA setting vs in the community. [However, one study shows] that this is not a VA-specific phenomenon and that there is an increase in overtreatment of men with limited longevity in a Medicare population as well,” Daskivich noted.

 

Is Overtreatment All Bad?

Overtreatment of prostate cancer, especially in cases where the cancer is unlikely to progress or cause symptoms, can lead to significant physical, psychological, and financial harms, Christopher Anderson, MD, urologist with Columbia University Irving Medical Center in New York City, who wasn’t involved in the study, noted in an interview.

In the study by Daskivich and colleagues, over three quarters of the overtreatment was radiation therapy, which carries the risk for urinary, bowel, and sexual issues.

“Overscreening, which can lead to overtreatment, is a core issue,” Anderson said. It’s easy to order a “simple” prostate-specific antigen blood test, but in an older man with limited LE, that can lead to a host of further testing, he said.

Stopping the pipeline of overscreening that then feeds into the cascade of overtreatment is the first step in addressing the problem of prostate cancer overtreatment, Nancy Li Schoenborn, MD, MHS, with Johns Hopkins University School of Medicine, Baltimore, and Louise C. Walter, MD, with University of California San Francisco, wrote in an editorial in JAMA Internal Medicine.

Considering LE during screening decision-making is “fundamental to reducing harms of prostate cancer overdiagnosis and overtreatment” because limited LE increases the likelihood of experiencing “harms all along the diagnostic and treatment cascade following screening,” the editorial writers said.

The time spent diagnosing, monitoring, and treating asymptomatic prostate cancer in men with limited LE distracts from monitoring and treating chronic symptomatic life-limiting illnesses, they noted.

 

Tough to Talk About?

Anderson noted that, in general, doctors are not great at estimating and counseling patients on LE. “It’s sometimes difficult to have that conversation,” he said.

Daskivich said physicians may fail to include average LE when advising patients on treatments because they believe that the patients do not want to discuss this topic. “Yet, in interviews with patients, we found that prostate cancer patients reported they wanted this information,” he continued, in an interview.

Solving the problem of overscreening and overtreatment will require a “multifaceted approach, including improving access to life expectancy data at the point of care for providers, educating providers on how to communicate this information, and improving data sources to predict longevity,” Daskivich said.

He said it’s equally important to note that some men with prostate cancer may choose treatment even if they have a limited longevity.

“Not all patients will choose conservative management, even if it is recommended by guidelines. However, they need to be given the opportunity to make a good decision for themselves with the best possible data,” Daskivich said.

This work was supported in part by a US Department of VA Merit Review. Daskivich reported receiving personal fees from the Medical Education Speakers Network, EDAP, and RAND; research support from Lantheus and Janssen; and a patent pending for a system for healthcare visit quality assessment outside the submitted work. Schoenborn, Walter, and Anderson had no relevant disclosures.

 

A version of this article appeared on Medscape.com.

Overtreatment of men with prostate cancer and limited life expectancy (LE) has persisted in the era of active surveillance and worsened in some instances, according to a new study.

“Overtreatment of men with limited longevity for intermediate- and high-risk tumors has not only failed to improve but has actually worsened over the last 20 years,” Timothy Daskivich, MD, MSHPM, with Cedars-Sinai Medical Center, Los Angeles, said in an interview.

“Many doctors assume that the increase in uptake of active surveillance for low-risk prostate cancers has solved the problem of overtreatment, but this trend has not affected overtreatment of men with low likelihood of living long enough to benefit from treatment who have higher-risk tumors,” Daskivich said.

The study was published online on November 11 in JAMA Internal Medicine.

‘Concerning’ Real-World Data

For men with low- and intermediate-risk prostate cancer expected to live fewer than 10 years, prostate cancer screening and aggressive treatment are not recommended.

Daskivich and colleagues analyzed data on 243,928 men (mean age, 66 years) in the Veterans Affairs (VA) Health System with clinically localized prostate cancer diagnosed between 2000 and 2019.

About 21% had LE < 10 years, and about 4% had LE < 5 years, according to the validated age-adjusted Prostate Cancer Comorbidity Index.

Overtreatment was defined as aggressive treatment (surgery or radiation) in those with LE < 10 years and low- to intermediate-risk disease and in those with LE < 5 years and high-risk disease, in line with current guidelines.

Among men with LE < 10 years, the proportion of men overtreated with surgery or radiotherapy for low-risk disease decreased 22% but increased 22% for intermediate-risk disease during the study period.

Among men with LE < 5 years, the proportion of men treated with definitive treatment for high-risk disease increased 29%.

“While lower-risk tumors are treated less aggressively across the board, including in men with limited longevity, it seems that we are more indiscriminately treating men with higher-risk disease without considering their expected longevity,” Daskivich said in an interview.

 

Is This Happening in the General US Population?

Daskivich noted that the sample included a large sample of men diagnosed with localized prostate cancer in the VA Health System.

“Rates of overtreatment are likely to be lower in the VA [Health System], so the problem may be worse in the community setting. The VA [Health System] has been exemplary in its uptake of active surveillance for low-risk cancers, leading the effort to reduce overtreatment of men with low-risk cancers. However, the problem of overtreatment of men with limited longevity persists in the VA [Health System], underscoring the pervasiveness of this problem,” he explained.

“We don’t have a perfect head-to-head comparison of overtreatment in the VA setting vs in the community. [However, one study shows] that this is not a VA-specific phenomenon and that there is an increase in overtreatment of men with limited longevity in a Medicare population as well,” Daskivich noted.

 

Is Overtreatment All Bad?

Overtreatment of prostate cancer, especially in cases where the cancer is unlikely to progress or cause symptoms, can lead to significant physical, psychological, and financial harms, Christopher Anderson, MD, urologist with Columbia University Irving Medical Center in New York City, who wasn’t involved in the study, noted in an interview.

In the study by Daskivich and colleagues, over three quarters of the overtreatment was radiation therapy, which carries the risk for urinary, bowel, and sexual issues.

“Overscreening, which can lead to overtreatment, is a core issue,” Anderson said. It’s easy to order a “simple” prostate-specific antigen blood test, but in an older man with limited LE, that can lead to a host of further testing, he said.

Stopping the pipeline of overscreening that then feeds into the cascade of overtreatment is the first step in addressing the problem of prostate cancer overtreatment, Nancy Li Schoenborn, MD, MHS, with Johns Hopkins University School of Medicine, Baltimore, and Louise C. Walter, MD, with University of California San Francisco, wrote in an editorial in JAMA Internal Medicine.

Considering LE during screening decision-making is “fundamental to reducing harms of prostate cancer overdiagnosis and overtreatment” because limited LE increases the likelihood of experiencing “harms all along the diagnostic and treatment cascade following screening,” the editorial writers said.

The time spent diagnosing, monitoring, and treating asymptomatic prostate cancer in men with limited LE distracts from monitoring and treating chronic symptomatic life-limiting illnesses, they noted.

 

Tough to Talk About?

Anderson noted that, in general, doctors are not great at estimating and counseling patients on LE. “It’s sometimes difficult to have that conversation,” he said.

Daskivich said physicians may fail to include average LE when advising patients on treatments because they believe that the patients do not want to discuss this topic. “Yet, in interviews with patients, we found that prostate cancer patients reported they wanted this information,” he continued, in an interview.

Solving the problem of overscreening and overtreatment will require a “multifaceted approach, including improving access to life expectancy data at the point of care for providers, educating providers on how to communicate this information, and improving data sources to predict longevity,” Daskivich said.

He said it’s equally important to note that some men with prostate cancer may choose treatment even if they have a limited longevity.

“Not all patients will choose conservative management, even if it is recommended by guidelines. However, they need to be given the opportunity to make a good decision for themselves with the best possible data,” Daskivich said.

This work was supported in part by a US Department of VA Merit Review. Daskivich reported receiving personal fees from the Medical Education Speakers Network, EDAP, and RAND; research support from Lantheus and Janssen; and a patent pending for a system for healthcare visit quality assessment outside the submitted work. Schoenborn, Walter, and Anderson had no relevant disclosures.

 

A version of this article appeared on Medscape.com.

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Mon, 11/18/2024 - 14:13

Does Radiation Timing Affect QOL After Prostate Surgery?

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TOPLINE:

Receiving radiotherapy after prostatectomy does negatively affect long-term health-related quality of life, including sexual function, urinary incontinence, and urinary irritation, but the timing of radiation after prostatectomy — within a year or over a year from surgery — does not appear to significantly affect patients’ quality of life over the long term, a recent analysis finds.

METHODOLOGY:

  • Delaying radiotherapy after prostatectomy can help avoid overtreatment and mitigate genitourinary and erectile toxic effects. However, few studies have compared long-term patient-reported health-related quality-of-life outcomes on the basis of the timing of postprostatectomy radiotherapy.
  • Researchers evaluated 1203 men (median age, 60.5 years; 92% were White and 6.8% were Black) with localized prostate cancer who underwent radical prostatectomy from the PROST-QA (2003-2006) and RP2 Consortium (2010-2013). Among these patients, 1082 underwent surgery only, 57 received early radiotherapy (within 12 months of surgery), and 64 underwent late radiotherapy (12 months or more after surgery).
  • Patients who received early radiotherapy were more likely to receive androgen deprivation therapy than those who underwent late radiotherapy (40.4% vs 12.5%; P < .001).
  • Primary outcome was health-related quality of life measured using the Expanded Prostate Cancer Index Composite at baseline, 2, 6, and 12 months, and annually after that. Health-related quality-of-life measures included sexual function, urinary incontinence, urinary irritation and/or obstruction, and bowel or rectal function.
  • The median follow-up duration was 85.6 months.

TAKEAWAY:

  • Postprostatectomy radiotherapy was associated with a significantly greater decline in health-related quality of life across all domains, including sexual function and urinary incontinence.
  • Patients who received early radiation initially experienced worse urinary incontinence and sexual health, compared with patients in the late group, but the early group also had higher-risk disease and were more likely to receive concurrent androgen deprivation therapy.
  • In the long term, the early radiotherapy group experienced more pronounced recovery of sexual function, urinary irritation, and urinary incontinence than the late radiotherapy group.
  • Ultimately, patients in the early radiotherapy group had similar, potentially better, long-term health-related quality-of-life domain scores than those in the late group over the long term. For instance, the likelihood of being pad free increased for patients treated early with radiation, while it decreased for those treated late. In patients who received early radiation, the rate of freedom from pad use increased from 39% before radiation to 67% at the sixth follow-up visit after radiation, while it decreased from 73% to 48% in those who received late radiation.

IN PRACTICE:

“Long-term patient-reported sexual, incontinence, and urinary irritative outcomes did not significantly differ between early vs late postprostatectomy [radiotherapy],” the authors said. In fact, “men receiving early [radiation] experienced greater recovery of these toxicity domains and achieved similar, and possibly better, domain scores as those receiving late [radiation] at long-term follow-up.” Overall, “these results may help guide treatment counseling and support consideration of early [radiotherapy] after prostatectomy for men at particularly high risk of recurrence and metastasis.”

 

 

SOURCE:

The study, led by Sagar A. Patel, MD, MSc, Emory University in Atlanta, was published online in JAMA Network Open.

LIMITATIONS:

The early and late postprostatectomy radiotherapy groups were relatively small and underpowered to detect statistically significant differences between groups. The study has a nonrandomized design, which may introduce unaccounted for imbalances among the different groups. The study did not directly compare health-related quality of life between patients receiving adjuvant vs salvage radiotherapy.

DISCLOSURES:

This study received funding from National Institutes of Health grants and the Paul Calabresi Career Development Award for Clinical Oncology. Several authors reported receiving personal fees, grants, and having other ties with various sources. Additional disclosures are noted in the original article.

A version of this article appeared on Medscape.com.

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TOPLINE:

Receiving radiotherapy after prostatectomy does negatively affect long-term health-related quality of life, including sexual function, urinary incontinence, and urinary irritation, but the timing of radiation after prostatectomy — within a year or over a year from surgery — does not appear to significantly affect patients’ quality of life over the long term, a recent analysis finds.

METHODOLOGY:

  • Delaying radiotherapy after prostatectomy can help avoid overtreatment and mitigate genitourinary and erectile toxic effects. However, few studies have compared long-term patient-reported health-related quality-of-life outcomes on the basis of the timing of postprostatectomy radiotherapy.
  • Researchers evaluated 1203 men (median age, 60.5 years; 92% were White and 6.8% were Black) with localized prostate cancer who underwent radical prostatectomy from the PROST-QA (2003-2006) and RP2 Consortium (2010-2013). Among these patients, 1082 underwent surgery only, 57 received early radiotherapy (within 12 months of surgery), and 64 underwent late radiotherapy (12 months or more after surgery).
  • Patients who received early radiotherapy were more likely to receive androgen deprivation therapy than those who underwent late radiotherapy (40.4% vs 12.5%; P < .001).
  • Primary outcome was health-related quality of life measured using the Expanded Prostate Cancer Index Composite at baseline, 2, 6, and 12 months, and annually after that. Health-related quality-of-life measures included sexual function, urinary incontinence, urinary irritation and/or obstruction, and bowel or rectal function.
  • The median follow-up duration was 85.6 months.

TAKEAWAY:

  • Postprostatectomy radiotherapy was associated with a significantly greater decline in health-related quality of life across all domains, including sexual function and urinary incontinence.
  • Patients who received early radiation initially experienced worse urinary incontinence and sexual health, compared with patients in the late group, but the early group also had higher-risk disease and were more likely to receive concurrent androgen deprivation therapy.
  • In the long term, the early radiotherapy group experienced more pronounced recovery of sexual function, urinary irritation, and urinary incontinence than the late radiotherapy group.
  • Ultimately, patients in the early radiotherapy group had similar, potentially better, long-term health-related quality-of-life domain scores than those in the late group over the long term. For instance, the likelihood of being pad free increased for patients treated early with radiation, while it decreased for those treated late. In patients who received early radiation, the rate of freedom from pad use increased from 39% before radiation to 67% at the sixth follow-up visit after radiation, while it decreased from 73% to 48% in those who received late radiation.

IN PRACTICE:

“Long-term patient-reported sexual, incontinence, and urinary irritative outcomes did not significantly differ between early vs late postprostatectomy [radiotherapy],” the authors said. In fact, “men receiving early [radiation] experienced greater recovery of these toxicity domains and achieved similar, and possibly better, domain scores as those receiving late [radiation] at long-term follow-up.” Overall, “these results may help guide treatment counseling and support consideration of early [radiotherapy] after prostatectomy for men at particularly high risk of recurrence and metastasis.”

 

 

SOURCE:

The study, led by Sagar A. Patel, MD, MSc, Emory University in Atlanta, was published online in JAMA Network Open.

LIMITATIONS:

The early and late postprostatectomy radiotherapy groups were relatively small and underpowered to detect statistically significant differences between groups. The study has a nonrandomized design, which may introduce unaccounted for imbalances among the different groups. The study did not directly compare health-related quality of life between patients receiving adjuvant vs salvage radiotherapy.

DISCLOSURES:

This study received funding from National Institutes of Health grants and the Paul Calabresi Career Development Award for Clinical Oncology. Several authors reported receiving personal fees, grants, and having other ties with various sources. Additional disclosures are noted in the original article.

A version of this article appeared on Medscape.com.

 

TOPLINE:

Receiving radiotherapy after prostatectomy does negatively affect long-term health-related quality of life, including sexual function, urinary incontinence, and urinary irritation, but the timing of radiation after prostatectomy — within a year or over a year from surgery — does not appear to significantly affect patients’ quality of life over the long term, a recent analysis finds.

METHODOLOGY:

  • Delaying radiotherapy after prostatectomy can help avoid overtreatment and mitigate genitourinary and erectile toxic effects. However, few studies have compared long-term patient-reported health-related quality-of-life outcomes on the basis of the timing of postprostatectomy radiotherapy.
  • Researchers evaluated 1203 men (median age, 60.5 years; 92% were White and 6.8% were Black) with localized prostate cancer who underwent radical prostatectomy from the PROST-QA (2003-2006) and RP2 Consortium (2010-2013). Among these patients, 1082 underwent surgery only, 57 received early radiotherapy (within 12 months of surgery), and 64 underwent late radiotherapy (12 months or more after surgery).
  • Patients who received early radiotherapy were more likely to receive androgen deprivation therapy than those who underwent late radiotherapy (40.4% vs 12.5%; P < .001).
  • Primary outcome was health-related quality of life measured using the Expanded Prostate Cancer Index Composite at baseline, 2, 6, and 12 months, and annually after that. Health-related quality-of-life measures included sexual function, urinary incontinence, urinary irritation and/or obstruction, and bowel or rectal function.
  • The median follow-up duration was 85.6 months.

TAKEAWAY:

  • Postprostatectomy radiotherapy was associated with a significantly greater decline in health-related quality of life across all domains, including sexual function and urinary incontinence.
  • Patients who received early radiation initially experienced worse urinary incontinence and sexual health, compared with patients in the late group, but the early group also had higher-risk disease and were more likely to receive concurrent androgen deprivation therapy.
  • In the long term, the early radiotherapy group experienced more pronounced recovery of sexual function, urinary irritation, and urinary incontinence than the late radiotherapy group.
  • Ultimately, patients in the early radiotherapy group had similar, potentially better, long-term health-related quality-of-life domain scores than those in the late group over the long term. For instance, the likelihood of being pad free increased for patients treated early with radiation, while it decreased for those treated late. In patients who received early radiation, the rate of freedom from pad use increased from 39% before radiation to 67% at the sixth follow-up visit after radiation, while it decreased from 73% to 48% in those who received late radiation.

IN PRACTICE:

“Long-term patient-reported sexual, incontinence, and urinary irritative outcomes did not significantly differ between early vs late postprostatectomy [radiotherapy],” the authors said. In fact, “men receiving early [radiation] experienced greater recovery of these toxicity domains and achieved similar, and possibly better, domain scores as those receiving late [radiation] at long-term follow-up.” Overall, “these results may help guide treatment counseling and support consideration of early [radiotherapy] after prostatectomy for men at particularly high risk of recurrence and metastasis.”

 

 

SOURCE:

The study, led by Sagar A. Patel, MD, MSc, Emory University in Atlanta, was published online in JAMA Network Open.

LIMITATIONS:

The early and late postprostatectomy radiotherapy groups were relatively small and underpowered to detect statistically significant differences between groups. The study has a nonrandomized design, which may introduce unaccounted for imbalances among the different groups. The study did not directly compare health-related quality of life between patients receiving adjuvant vs salvage radiotherapy.

DISCLOSURES:

This study received funding from National Institutes of Health grants and the Paul Calabresi Career Development Award for Clinical Oncology. Several authors reported receiving personal fees, grants, and having other ties with various sources. Additional disclosures are noted in the original article.

A version of this article appeared on Medscape.com.

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