CUA 2018: Impact of 5 Alpha Reductase Inhibitors and Alpha Blockers for BPH on Prostate Cancer Incidence and Mortality

Halifax, Nova Scotia (UroToday.com) Nickel J. Curtis, MD presented a study demonstrating the effect of 5 alpha reductase inhibitors (5ARI) and alpha-blocker on prostate cancer (PC) incidence and mortality using a large population-based database in Canada.

5ARIs may be used to manage and/or prevent progression of lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH) and to reduce the risk of urinary retention and future prostate-related surgery. Evidence from large BPH trials has shown that there is a 40% relative risk reduction of PC diagnosis (COMBAT randomized trial).1 Similar findings in other BPH trials showed a 34% risk reduction in a meta-analysis.2

Evidence from PC prevention trials such as PCPT 3,4 and REDUCE 5,6 show that there is a 25% lower incidence of diagnosed PC among men randomized to 5ARIs. Risk reduction was substantiated by a 2010 systemic review.7 However, these trials showed that 5ARIs cause an increase in the rate of diagnosis of Gleason 8-10 PC. This was both an absolute and a relative increase. In the PCPT a 1% risk increase was demonstrated, and in the REDUCE trial, this was an absolute increase of 0.5%.  It is not clear if this is a sampling artifact. Therefore, the authors aimed to investigate the use of 5ARIs and alpha blockers among BPH diagnosed men in relation to PC incidence, severity, and mortality.

This was a retrospective 20-year cohort study in Saskatchewan, Canada, including male patients aged 40-89 between 1995 and 2014.  The authors analyzed the incidence of PC diagnosis, metastatic PC, Gleason 8-10 PC, and PC mortality among 5ARIs users (n=4571 men), alpha-blocker users (n=7764 men), and non-users (n=11677 men).

A multivariable model to assess PC diagnosis was created and adjusted for age at index date, baseline use of lipid-lowering drugs (statins and non-statins lipid-lowering medications), and baseline cardiometabolic conditions (diabetes, hypertension, heart disease, and/or hyperlipidemia). The model demonstrated that 5ARIS had an age-adjusted hazard ratio (HR) of 0.6 (0.52-0.68, p<0.001) and alpha blockers had an age-adjusted HR of 0.56 (0.49-0.65, p<0.001) (Figure 1). When assessing PC mortality, 5ARIs and alpha blockers were not statistically significant predictors of worse PC mortality. Interestingly, earlier index years – presumably longer duration use – were inversely correlated with PC outcomes.

Figure 1 – Prostate cancer incidence among 5ARIs and alpha blockers users compared to non-users:
UroToday CUA 2018 Prostate cancer incidence among 5ARIs and alpha blockers users compared to non users 1

UroToday CUA 2018 Prostate cancer incidence among 5ARIs and alpha blockers users compared to non users 2
Summarizing the results, in comparison to non-users and to alpha-blocker users, 5ARIs had >35% lower risk of PC diagnosis. Compared to non-users, alpha blockers had 11% lower risk of PC diagnosis. For both 5ARIS and alpha blockers users, approximately 30% higher risk of Gleason 8-10 cancer was demonstrated, compared to non-users. Overall, no significant increase in metastatic PC or PC mortality was noted among 5ARI and alpha blockers compared to non-users.

The strengths of this study include its large number of patients (>200,000 men), long follow-up time (up to 20 years), and relatively large number of events for the main outcomes of interest. The limitations of this study include its retrospective nature, with a clear selection bias, missing data, and the limited data available on cancer progression and treatment.

Curtis summarized his talk with some take-home messages for urologists managing BPH. 5ARIs use was associated with lower risk of a PC diagnosis. The risk of high grade PC was higher among both 5ARIs and alpha blockers users compared to non-users. However, this increased high-grade risk did not translate into higher risk of PC progression or mortality. Lastly, this study is reassuring for BPH patients, but cannot be used to recommend a formal 5ARI cancer prevention strategy.


References:
1. Roehrborn et al. 2011
2. Monga et al. 2013
3. Thompson et al. 2003
4. Thompson et al. 2013
5.  Andriole et al. 2010
6.  Grubb et al. 2013
7.  Wilt et al. 2010

Presented by: Nickel J. Curtis, MD, National Institute of Health

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, @GoldbergHanan at the 73rd Canadian Urological Association Annual Meeting - June 23 - 26, 2018 - Halifax, Nova Scotia
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