5-Alpha Reductase Inhibitors and Prostate Cancer Mortality among Men with Regular Access to Screening and Health Care

Vaselkiv, Jane B.; Ceraolo, Carl; Wilson, Kathryn M.; Pernar, Claire H.; Rencsok, Emily M; Stopsack, Konrad H.; Grob, Sydney; Plym, Anna; Giovannucci, Edward; Olumi, Aria F.; Kibel, Adam S.; Preston, Mark A.; Mucci, Lorelei A.

doi:10.1158/1055-9965.epi-21-1234

Cited by 5 publications

(4 citation statements)

References 37 publications

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“…Among 1200 unique records screened, 11 studies met our inclusion criteria (Table). One study was an RCT, and 10 were registry-based cohort studies.…”

Section: Resultsmentioning

confidence: 99%

Association Between 5α-Reductase Inhibitors and Prostate Cancer Mortality

et al. 2023

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ImportanceRecently, several large, high-quality analyses have shown opposing results regarding the association between 5α-reductase inhibitor (5-ARI) use and prostate cancer (PCa) mortality.ObjectiveTo systematically evaluate the current evidence regarding 5-ARI use and PCa mortality.Data SourcesA literature search began in and was conducted through August 2022 using PubMed/Medline, Embase, and Web of Science databases.Study SelectionStudies were deemed eligible if they included male patients of any age who were 5-ARI users and were compared with those who were nonusers if they analyzed PCa mortality in randomized clinical trials and prospective or retrospective cohort studies.Data Extraction and SynthesisThis study was reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Adjusted hazard ratios (HRs) were extracted from published articles. Data analysis was performed in August 2022.Main Outcomes and MeasuresThe primary outcome was PCa mortality among 5-ARI users vs nonusers. The inverse variance method with adjusted HRs and random-effect models were used to determine the association between 5-ARI use and PCa mortality. Two subgroup analyses were performed to assess the effect of 2 main confounders: prostate-specific antigen level and PCa diagnosis at baseline.ResultsAmong 1200 unique records screened, 11 studies met the inclusion criteria. A total of 3 243 575 patients were included: 138 477 users of 5-ARI and 3 105 098 nonusers. There was no statistically significant association between 5-ARI use and PCa mortality (adjusted HR, 1.04; 95% CI, 0.80-1.35; P = .79). No significant association was found when the analysis was restricted to studies that excluded patients with a diagnosis of PCa at baseline (adjusted HR, 1.00; 95% CI, 0.60-1.67; P = .99) or the analysis was restricted to prostate-specific antigen–adjusted studies (adjusted HR, 0.76; 95% CI, 0.57-1.03; P = .08).Conclusions and RelevanceThis systematic review and meta-analysis, which draws on 2 decades of epidemiologic literature and includes more than 3 million patients, found no statistically significant association between 5-ARI use and PCa mortality but provides important data to inform clinical care.

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“…Among 1200 unique records screened, 11 studies met our inclusion criteria (Table). One study was an RCT, and 10 were registry-based cohort studies.…”

Section: Resultsmentioning

confidence: 99%

Association Between 5α-Reductase Inhibitors and Prostate Cancer Mortality

et al. 2023

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“…Recent clinical studies have shown the benefit of combined hormone and radiation therapy in terms of local control and biochemical disease-free survival [18] . There is in addition now emerging evidence of a benefit in overall survival, though more data is needed here [18][19] .…”

Section: Adjuvant Therapy Of Localised Prostate Cancermentioning

confidence: 99%

“…The results of radical prostatectomy and external beam radiotherapy are poor in patients with locally advanced disease. After prostatectomy, 54% of patients with capsular penetration and low-grade tumours remain free of biochemical relapse at 10 years, while only 42% with high grade tumours are disease free [19] . Ten-year survival rates in patients with locally advanced disease treated with radiotherapy are between 35% and 45%.…”

Section: Adjuvant Therapy Of Localised Prostate Cancermentioning

confidence: 99%

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The pathophysiologic basis of prostate cancer review

Manoharan¹,

Gottam²

2022

Int. J. Sci. Res. Arch.

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Worldwide, prostate cancer is the most commonly diagnosed malignancy and the sixth leading cause of cancer death in men. Diagnosis is primarily based on prostate-specific antigen (PSA) testing, MRI scans, and prostate tissue biopsies, although PSA testing for screening remains controversial. New diagnostic technologies including risk stratification bioassay tests, germline testing, and various PET scans are now available. When the cancer is limited to the prostate, it is considered localized and potentially curable. If the disease has spread outside the prostate, bisphosphonates, rank ligand inhibitors, hormonal treatment, chemotherapy, radiopharmaceuticals, immunotherapy, focused radiation, and other targeted therapies can be used. This activity is a current, comprehensive review of the evaluation and management of patients with prostate cancer and highlights the role of the interprofessional team in improving care for affected patients. Metastatic castration-resistant prostate cancer (mCRPC) remains a terminal diagnosis with an aggressive disease course despite currently approved therapeutics. Despite many recent advances in the therapy for metastatic castration-resistant prostate cancer (mCRPC), the disease remains incurable, although men suffering from this disease are living considerably longer.

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5-α Reductase Inhibitors and Prostate Cancer Mortality

Hamilton,

Chavarriaga,

Khurram

et al. 2024

JAMA Netw Open

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Importance5-alpha-reductase-inhibitors (5-ARIs) are approved for treating benign prostatic hyperplasia (BPH) and have been found to reduce prostate cancer (PCa) risk by 25%. However, trials also have shown 5-ARIs to be associated with high-grade PCa. Whether 5-ARIs increase mortality among those with a diagnosis of PCa remains unclear.ObjectiveTo determine long-term outcomes of clinically localized PCa arising in individuals taking 5-ARIs compared with nonusers.Design, Setting, and ParticipantsThis population-based cohort study was conducted between January 2003 and October 2017. Eligible participants were men aged 65 years or older in Ontario, Canada, who developed clinically localized PCa with complete pathological abstraction from the Ontario Health Administrative Databases. Data analysis occurred from November 2017 to November 2022.Exposure5-ARIs before PCa diagnosis.Main Outcomes and MeasuresThe primary outcomes were overall mortality and PCa-specific mortality. Cause-specific hazard models with inverse probability treatment weights (IPTW) were used to examine associations of 5-ARI use with mortality outcomes. Sensitivity analyses based on prediagnostic 5-ARI use, Gleason score, comorbidity, 5-ARI indication, prostate-specific antigen modeling, and statin use were also performed.ResultsThe cohort included 19 938 patients with PCa. Of these, 2112 (10.6%; median [IQR] age, 74 [70-79] years) were 5-ARI users and 17 826 (89.4%; median [IQR] age, 71 [68-76] years) were nonusers. During a median (IQR) follow-up of 8.96 (6.28-12.17) years, 6053 (30.4%) died, including 1047 (5.3%) from PCa. 5-ARI use appeared to be associated with increased overall and PCa specific mortality in crude analyses; however, after IPTW, 5-ARI use was not associated with overall mortality (hazard ratio, 0.98; 95% CI, 0.90-1.07; P = .77) or PCa-specific mortality (hazard ratio, 1.02; 95% CI, 0.83-1.25; P = .84).Conclusions and RelevanceIn this population-based cohort study of 5-ARI use prior to PCa diagnosis including long-term follow-up and clinicopathologic details, prediagnostic 5-ARI use was not associated with PCa-specific or all-cause mortality. This study offers reassuring safety data for patients using 5-ARIs before PCa diagnosis for both BPH and chemopreventive reasons.

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5-Alpha Reductase Inhibitors and Prostate Cancer Mortality among Men with Regular Access to Screening and Health Care

Cited by 5 publications

References 37 publications

Association Between 5α-Reductase Inhibitors and Prostate Cancer Mortality

Association Between 5α-Reductase Inhibitors and Prostate Cancer Mortality

The pathophysiologic basis of prostate cancer review

5-α Reductase Inhibitors and Prostate Cancer Mortality

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