Association of Treatment With 5α-Reductase Inhibitors and Prostate Cancer Mortality Among Older Adults

Kumar, Abhishek; Nalawade, Vinit; Riviere, Paul; Sarkar, Reith; Parsons, John K.; Murphy, James D.; Rose, Brent S.

doi:10.1001/jamanetworkopen.2019.13612

Cited by 4 publications

(7 citation statements)

References 7 publications

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“…12,30 The present cohort study would benefit from an unprecedented covariate balance because, to our knowledge, no previous study has used matching methods when exploring the association between 5-ARIs and urological cancers. [3][4][5][6][7][8]18 The findings in this study align with those of a previous study by Mäkelä et al, 18 who observed lower BC death (HR, 0.84; 95% CI, 0.73-0.97) in patients who filled a 5-ARI prescription than in those who did not use the drug. Mäkelä et al 18 also observed fewer cystectomies (6.8% vs 9.4%) and chemotherapies (20.1% vs 22.8%) in patients with a 5-ARI prescription compared with those without.…”

Section: Discussionsupporting

confidence: 91%

“…The large Prostate Cancer Prevention Trial (PCPT) initially showed the prostate cancer–protective properties of 5-ARI, although high-grade prostate cancer was paradoxically higher in those receiving 5-ARI. This finding was validated by those of other cohort studies . In contrast, the association between 5-ARI and urothelial BC, another cancer experienced predominantly by males, remains unknown.…”

Section: Introductionsupporting

confidence: 73%

“…Propensity score matching is a validated strategy and widely used in pharmacovigilance studies to reduce bias and mimic long-term RCTs . The present cohort study would benefit from an unprecedented covariate balance because, to our knowledge, no previous study has used matching methods when exploring the association between 5-ARIs and urological cancers …”

Section: Discussionmentioning

confidence: 99%

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Association of 5α-Reductase Inhibitor Prescription With Bladder Cancer Progression in Males in South Korea

Kim

et al. 2023

JAMA Netw Open

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ImportanceThe antiandrogenic effect of the 5α-reductase inhibitor (5-ARI) has been investigated for its role in preventing male-predominant cancers. Although 5-ARI has been widely associated with prostate cancer, its association with urothelial bladder cancer (BC), another cancer experienced predominantly by males, has been less explored.ObjectiveTo assess the association between 5-ARI prescription prior to BC diagnosis and reduced risk of BC progression.Design, Setting, and ParticipantsThis cohort study analyzed patient claims data from the Korean National Health Insurance Service database. The nationwide cohort included all male patients with BC diagnosis in this database from January 1, 2008, to December 31, 2019. Propensity score matching was conducted to balance the covariates between 2 treatment groups: α-blocker only group and 5-ARI plus α-blocker group. Data were analyzed from April 2021 to March 2023.ExposureNewly dispensed prescriptions of 5-ARIs at least 12 months prior to cohort entry (BC diagnosis), with a minimum of 2 prescriptions filled.Main Outcomes and MeasuresThe primary outcomes were the risks of bladder instillation and radical cystectomy, and the secondary outcome was all-cause mortality. To compare the risk of outcomes, the hazard ratio (HR) was estimated using a Cox proportional hazards regression model and difference in restricted mean survival time analysis.ResultsThe study cohort initially included 22 845 males with BC. After propensity score matching, 5300 patients each were assigned to the α-blocker only group (mean [SD] age, 68.3 [8.8] years) and 5-ARI plus α-blocker group (mean [SD] age, 67.8 [8.6] years). Compared with the α-blocker only group, the 5-ARI plus α-blocker group had a lower risk of mortality (adjusted HR [AHR], 0.83; 95% CI, 0.75-0.91), bladder instillation (crude HR, 0.84; 95% CI, 0.77-0.92), and radical cystectomy (AHR, 0.74; 95% CI, 0.62-0.88). The differences in restricted mean survival time were 92.6 (95% CI, 25.7-159.4) days for all-cause mortality, 88.1 (95% CI, 25.2-150.9) days for bladder instillation, and 68.0 (95% CI, 31.6-104.3) days for radical cystectomy. The incidence rates per 1000 person-years were 85.59 (95% CI, 80.53-90.88) for bladder instillation and 19.57 (95% CI, 17.41-21.91) for radical cystectomy in the α-blocker only group and 66.43 (95% CI, 62.22-70.84) for bladder instillation and 13.56 (95% CI, 11.86-15.45) for radical cystectomy in the 5-ARI plus α-blocker group.Conclusions and relevanceResults of this study suggest an association between prediagnostic prescription of 5-ARI and reduced risk of BC progression.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

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Association of 5α-Reductase Inhibitor Prescription With Bladder Cancer Progression in Males in South Korea

Kim

et al. 2023

JAMA Netw Open

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“…However, in the radiomic feature selection phase, cases without kallikreins were included to improve sample size. Subsequently, to avoid bias brought by the effect that 5-alpha-reductase inhibitor (5-ARI) medication has on PSA and PSA-based kallikreins, [22][23][24] we identified cases that were not taking 5-ARI medication within 6 months of bpMRI examination and only included those in the modeling, validation and external testing phases. Inclusion of cases in each of the study phases is shown in Fig.…”

Section: Data Analyses and Modelingmentioning

confidence: 99%

Detection of Prostate Cancer Using Biparametric Prostate MRI, Radiomics, and Kallikreins: A Retrospective Multicenter Study of Men With a Clinical Suspicion of Prostate Cancer

Perez

Merisaari

Jambor

et al. 2021

Magnetic Resonance Imaging

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Background: Accurate detection of clinically significant prostate cancer (csPCa), Gleason Grade Group ≥ 2, remains a challenge. Prostate MRI radiomics and blood kallikreins have been proposed as tools to improve the performance of biparametric MRI (bpMRI). Purpose: To develop and validate radiomics and kallikrein models for the detection of csPCa. Study Type: Retrospective. Population: A total of 543 men with a clinical suspicion of csPCa, 411 (76%, 411/543) had kallikreins available and 360 (88%, 360/411) did not take 5-alpha-reductase inhibitors. Two data splits into training, validation (split 1: single center, n = 72; split 2: random 50% of pooled datasets from all four centers), and testing (split 1: 4 centers, n = 288; split 2: remaining 50%) were evaluated. Field strength/Sequence: A 3 T/1.5 T, TSE T2-weighted imaging, 3x SE DWI. Assessment: In total, 20,363 radiomic features calculated from manually delineated whole gland (WG) and bpMRI suspicion lesion masks were evaluated in addition to clinical parameters, prostate-specific antigen, four kallikreins, MRI-based qualitative (PI-RADSv2.1/IMPROD bpMRI Likert) scores.

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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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Association of Treatment With 5α-Reductase Inhibitors and Prostate Cancer Mortality Among Older Adults

Abstract: This cohort study examines the association between use of 5α-reductase inhibitors and prostate cancer mortality among US Medicare beneficiaries.

Cited by 4 publications

References 7 publications

Association of 5α-Reductase Inhibitor Prescription With Bladder Cancer Progression in Males in South Korea

Association of 5α-Reductase Inhibitor Prescription With Bladder Cancer Progression in Males in South Korea

Detection of Prostate Cancer Using Biparametric Prostate MRI, Radiomics, and Kallikreins: A Retrospective Multicenter Study of Men With a Clinical Suspicion of Prostate Cancer

Association Between 5α-Reductase Inhibitors and Prostate Cancer Mortality

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