5α-Reductase Inhibitors and Risk of High-Grade or Lethal Prostate Cancer

Purpose To develop an evidence-based guideline on the use of 5-α-reductase inhibitors (5-ARIs) for prostate cancer chemoprevention. Methods The American Society of Clinical Oncology (ASCO) Health Services Committee (HSC), ASCO Cancer Prevention Committee, and the American Urological Association Practice Guidelines Committee jointly convened a Panel of experts, who used the results from a systematic review of the literature to develop evidence-based recommendations on the use of 5-ARIs for prostate cancer chemoprevention. Results The systematic review completed for this guideline identified 15 randomized clinical trials that met the inclusion criteria, nine of which reported prostate cancer period prevalence. Conclusion Asymptomatic men with a prostate-specific antigen (PSA) ≤ 3.0 ng/mL who are regularly screened with PSA or are anticipating undergoing annual PSA screening for early detection of prostate cancer may benefit from a discussion of both the benefits of 5-ARIs for 7 years for the prevention of prostate cancer and the potential risks (including the possibility of high-grade prostate cancer). Men who are taking 5-ARIs for benign conditions such as lower urinary tract [obstructive] symptoms (LUTS) may benefit from a similar discussion, understanding that the improvement of LUTS relief should be weighed with the potential risks of high-grade prostate cancer from 5-ARIs (although the majority of the Panel members judged the latter risk to be unlikely). A reduction of approximately 50% in PSA by 12 months is expected in men taking a 5-ARI; however, because these changes in PSA may vary across men, and within individual men over time, the Panel cannot recommend a specific cut point to trigger a biopsy for men taking a 5-ARI. No specific cut point or change in PSA has been prospectively validated in men taking a 5-ARI.

Download Full-text

MP04-10 USE OF 5?-REDUCTASE INHIBITORS FOR BENIGN PROSTATIC HYPERTROPHY AND RISK OF HIGH-GRADE PROSTATE CANCER: A FRENCH POPULATION-BASED STUDY

The Journal of Urology ◽

10.1016/j.juro.2018.02.160 ◽

2018 ◽

Vol 199 (4S) ◽

Author(s):

Lucie-Marie SCAILTEUX ◽

Frédéric BALUSSON ◽

Emmanuel NOWAK ◽

Sébastien VINCENDEAU ◽

Nathalie RIOUX-LECLERCQ ◽

...

Keyword(s):

Prostate Cancer ◽

Benign Prostatic Hypertrophy ◽

Population Based ◽

Prostatic Hypertrophy ◽

High Grade ◽

French Population ◽

Population Based Study ◽

Reductase Inhibitors

Download Full-text

PCPT, MTOPS and the use of 5ARIs: a Canadian consensus regarding implications for clinical practice

Canadian Urological Association Journal ◽

10.5489/cuaj.33 ◽

2012 ◽

Vol 1 (1) ◽

Author(s):

Laurence Klotz ◽

Fred Saad

Keyword(s):

Prostate Cancer ◽

Clinical Practice ◽

Cancer Prevention ◽

Consensus Conference ◽

Consensus Meeting ◽

Medical Community ◽

High Grade ◽

Urologic Oncology ◽

Reductase Inhibitors ◽

Prostate Cancer Prevention

Objectives: Two large, recently published, definitive trials evaluated the benefitsof 5-alpha reductase inhibitors (5ARIs). The Prostate Cancer Prevention Trial(PCPT) tested the effect of finasteride for prostate cancer prevention and the Medical Therapy of Prostatic Symptoms (MTOPS) tested its effect in benign prostatic hyperplasia(BPH). Both trials were strongly positive. However, the role of 5ARIs inthe clinical management of patients remains controversial. The consensus conference,which forms the basis for this report, attempted to develop an expertopinion, based on these studies, as to the optimal use of 5ARIs in patient management.Methods: The Canadian Consensus Meeting, organized by the Canadian Urology Research Consortium and the Canadian Urologic Oncology Group, held inToronto on May 7, 2006, focused on the new data from the PCPT and the MTOPS study. Internationally recognized experts and clinicians discussedthe implications of these data on clinical practice and issued a recommendationon the optimal management of patients with BPH.Results: The Consensus meeting agreed on the following recommendations:1. The overall results from the PCPT and MTOPS studies are of importanceto the urologic, as well as to the greater medical, community.2. Prostate management guidelines should be updated to include the resultsfrom both the MTOPS and the PCPT studies.3. In the PCPT, the incidence of high-grade cancer was higher in the finasteridetreatedgroup (6.4%), compared with the placebo group (5.1%). Subsequentanalyses strongly suggest that this increased prevalence was owing to a detectionbias caused by the reduction in prostate volume in patients takingfinasteride, compared with patients taking placebo. This resulted in animproved detection at biopsy of high-grade cancer in the finasteride group.4. In men who have large prostates and lower urinary tract symptoms (LUTS),5ARIs should be considered, both for the treatment of BPH and for prostatecancer risk reduction.5. For men who are concerned about prostate cancer, it is appropriate to discusschemoprevention with finasteride.6. Urologists are encouraged to disseminate these recommendations amongother healthcare professionals.

Download Full-text

Use of 5α-reductase inhibitors for benign prostate hypertrophy and risk of high grade prostate cancer: a French population-based study

BJU International ◽

10.1111/bju.14495 ◽

2018 ◽

Vol 123 (2) ◽

pp. 293-299 ◽

Cited By ~ 2

Author(s):

Lucie-Marie Scailteux ◽

Nathalie Rioux-Leclercq ◽

Sébastien Vincendeau ◽

Frédéric Balusson ◽

Emmanuel Nowak ◽

...

Keyword(s):

Prostate Cancer ◽

Population Based ◽

High Grade ◽

French Population ◽

Population Based Study ◽

Benign Prostate Hypertrophy ◽

Reductase Inhibitors ◽

Benign Prostate

Download Full-text

High-grade prostate cancer and biochemical recurrence after radical prostatectomy among men using 5α-reductase inhibitors and alpha-blockers

The Prostate ◽

10.1002/pros.22638 ◽

2013 ◽

Vol 73 (9) ◽

pp. 923-931 ◽

Cited By ~ 4

Author(s):

Teemu J. Murtola ◽

Paula M. Kujala ◽

Teuvo L.J. Tammela

Keyword(s):

Prostate Cancer ◽

Radical Prostatectomy ◽

Biochemical Recurrence ◽

High Grade ◽

Alpha Blockers ◽

Reductase Inhibitors

Download Full-text

The Case for Prostate Cancer Risk Reduction by 5-Alpha Reductase Inhibitors

American Society of Clinical Oncology Educational Book ◽

10.14694/edbook_am.2012.32.110 ◽

2012 ◽

pp. 92-95

Author(s):

Youssef S. Tanagho ◽

Gerald L. Andriole

Keyword(s):

Prostate Cancer ◽

Cancer Risk ◽

Risk Reduction ◽

Specific Antigen ◽

Prostate Cancer Risk ◽

Public Health Problem ◽

High Grade ◽

Reductase Inhibitors ◽

5 Alpha Reductase Inhibitors ◽

Cancer Risk Reduction

Overview: Prostate cancer remains a significant public health problem. The current approach with prostate-specific antigen (PSA)-based screening has questionable effects on prostate cancer–specific mortality but is clearly associated with overdiagnosis of prostate cancer, especially relatively low-risk and low-volume tumors. Methods to decrease overdiagnosis include alterations in screening practices and, potentially, the use of 5-alpha reductase inhibitors. This article reviews the major trials that have evaluated 5-alpha reductase inhibitors in this setting: the Prostate Cancer Prevention Trial (PCPT) and the Reduction by Dutasteride Prostate Cancer Events Trial (REDUCE). Although these trials enrolled different patient populations, their findings are complementary and suggest a potential role for these agents in prostate cancer risk reduction. Use of 5-alpha reductase inhibitors results in an approximate 25% reduction in the detection of prostate cancer, reduces diagnosis of high-grade prostatic intraepithelial neoplasia (PIN), and improves benign prostatic hyperplasia (BPH)-related outcomes and the performance of PSA as a diagnostic test for aggressive prostate cancer. Side effects occur in a small percentage of men and consist of decreased sexual function and libido as well as gynecomastia. The risk of high-grade tumor development while receiving these agents is uncertain.

Download Full-text

Impact of 5-ALPHA reductase inhibitor use on prostate cancer risk at the time of urology referral.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.6_suppl.226 ◽

2021 ◽

Vol 39 (6_suppl) ◽

pp. 226-226

Author(s):

James T Kearns ◽

Justin T. Matulay ◽

William E. Anderson ◽

Timothy C. Hetherington ◽

Claud Grigg ◽

...

Keyword(s):

Prostate Cancer ◽

Demographic Data ◽

Laboratory Data ◽

Prostate Cancer Risk ◽

Collaborative Group ◽

Ambulatory Setting ◽

High Grade ◽

Reductase Inhibitors ◽

Psa Testing ◽

The Impact

226 Background: 5-alpha reductase inhibitors (5-ARIs) are commonly used medications for the treatment of lower urinary tract symptoms caused by benign prostatic hyperplasia. One of the consequences of 5-ARI use is a 50% drop in serum PSA without a concomitant reduction in prostate cancer (PCa) risk. Previous work has suggested that 5-ARI use is associated with worse PCa-specific outcomes. The objective of this study was to evaluate the impact of 5-ARI use on patients’ PCa risk at the time of referral from primary care to urology. Methods: This retrospective cohort study included all men ≥ 40 years who had a PSA resulted between 2018-2019 and were seen in an ambulatory setting. PSA testing was determined through laboratory data in the electronic health record (EHR). Clinical and demographic data were collected for all men. 5-ARI use was determined through orders in the EHR. Men were assigned PCa risk according to both the Prostate Biopsy Collaborative Group (PBCG) and Prostate Cancer Prevention Trial (PCPT) risk calculators. PSA values were doubled for 5-ARI users prior to calculating risk. Referral to urology for PCa risk was determined using the narrative reason for referral associated with the referral order. Results: Between 2018-2019, 91,368 men had a PSA test, including 2,939 5-ARI users, and 88,429 non-users. Uncorrected median PSA and the proportion of men referred to urology for PCa risk were similar between the two groups (p = 0.60 and p = 0.17, respectively). Of men referred to urology for PCa risk, 5-ARI users had similar uncorrected PSA to non-users (p=0.86) but higher risk for high grade PCa once PSA correction was performed, median (IQR) 48% (24%) vs 28% (18%) using the PBCG and 21% (17%) vs 10% (10%) using the PCPT (p < 0.01 for both) (Table). Conclusions: Men taking 5-ARIs have significantly higher risk for high-grade PCa at time of referral to urology than non-users in this cohort. As the unadjusted PSA at referral to urology for PCa risk was the same between 5-ARI users and non-users, this indicates that the effect of 5-ARI use on serum PSA levels is not routinely accounted for when assessing PCa risk. Further study on interventions to account for 5-ARI use when screening for PCa are warranted. [Table: see text]

Download Full-text

Vasectomy and risk of lethal prostate cancer: A 24-year prospective study.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.5086 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 5086-5086

Author(s):

Lorelei A. Mucci ◽

Mohummad Minhaj Siddiqui ◽

Kathryn M Wilson ◽

Mara Meyer Epstein ◽

Jennifer R Rider ◽

...

Keyword(s):

Prostate Cancer ◽

Prospective Study ◽

Prostate Cancer Risk ◽

The United States ◽

High Grade ◽

Bony Metastasis ◽

Increased Risk ◽

Incidence And Mortality ◽

Incident Cases ◽

Lethal Prostate Cancer

5086 Background: In the United States, 10 to 15 percent of adult men have undergone a vasectomy. There is conflicting evidence whether vasectomy is associated with increased prostate cancer risk. Methods: We undertook a prospective study among 49,432 men in the US Health Professionals Follow-up Study. The men were age 40 to 75 years at baseline in 1986 and were followed prospectively for cancer incidence and mortality through 2010; 6,398 incident cases of prostate cancer were diagnosed, including 734 with high grade (Gleason 8 – 10) and 813 with cancer causing death or bony metastasis (lethal). We used cox regression models to calculate hazard ratios (HR, 95% confidence intervals) of the association between vasectomy and incidence of high grade and lethal prostate cancer, adjusting for potential confounders. We examined associations in the total cohort, and in a subset of 12,371 men highly screened by PSA in order to disentangle potential diagnostic bias. Results: At baseline, 22 percent of men reported having had a vasectomy. Men who had undergone vasectomy were at increased risk of high-grade (HR 1.23, 95% CI: 1.04-1.47) and lethal (HR 1.20, 95% CI: 1.01-1.43) prostate cancer. In the highly screened cohort, the association was similar for high-grade cancer, and even stronger for lethal disease (HR 1.56, 1.03-2.36). The risk of lethal prostate cancer was higher among men who had a vasectomy before age 38 years compared to at older ages. The increased risks with vasectomy could not be explained by differences in hormone levels, prevalence of sexually transmitted infections, or cancer treatments. Conclusions: Data from this study support the hypothesis that vasectomy is associated with a small increased incidence of aggressive prostate cancer defined as high grade cancer and disease causing death or bony metastasis. Differences in diagnostic intensity or confounding bias do not explain this elevated risk.

Download Full-text