Prostate Cancer Prevention (PDQ®): Prevention - Health Professional Information [NCI] - Opportunities for Prevention
Overall, there was no statistically significant difference of high-grade tumors for Gleason 8 to 10 cancers in years 1 to 4 (29 vs. 19, 0.9 vs. 0.6%; P = .15). However, in a retrospective analysis there was a statistically significant difference between years 3 to 4. Because this is a small retrospective subgroup, the finding of an increase in Gleason 8 to 10 cancers is of uncertain validity. However, the finding of no reduction in these cancers is more significant.
There are several plausible explanations for the failure of finasteride or dutasteride to reduce the incidence of Gleason 8 to 10 cancers. Because of this uncertainty, the evidence is currently insufficient to determine the effect of prophylaxis with these drugs on prostate cancer mortality.
Agents that are used for hormonal therapy of existing prostate cancers would be unsuitable for prostate cancer chemoprevention because of the cost and wide variety of side effects including sexual dysfunction, osteoporosis, and vasomotor symptoms (hot flushes). Newer antiandrogens may play a role as preventive agents in the future.
A Cochrane systematic review of all published studies of clinical outcome investigations of the prostate preventive effects of 5-alpha-reductase (5AR) inhibitors through 2010 that were at least one year in duration concluded that finasteride and dutasteride reduce the risk of being diagnosed with prostate among men who are screened regularly for prostate cancer. The review also concluded that mortality effects could not be assessed from these studies and that persistent use of these agents increased sexual and erectile dysfunction. The review was based on MEDLINE and Cochrane Collaboration Library computerized searches through June 2010 using Medical Subject Headings terms and text words ‘finasteride,' ‘dutasteride,' ‘neoplasms,' ‘azasteroids,' ‘reductase inhibitors' and ‘enzyme inhibitors' to identify randomized trials. Eight studies met the inclusion criteria. Only the Prostate Cancer Prevention Trial and the Reduction by Dutasteride of Prostate Cancer Events study were designed to assess the impact of 5AR inhibitors on prostate cancer period prevalence. Reviews of all eight studies concluded that compared with placebo, 5AR inhibitors resulted in 25% relative risk (RR) reduction in prostate cancers detected ‘for cause' [RR = 0.75; 95% CI, 0.67–0.83 and 1.4% absolute risk reduction (3.5% vs. 4.9%)]. Six trials of 5AR inhibitors versus placebo assessed prostate cancers detected overall. Among these there was a 26% RR reduction favoring 5AR inhibitors [RR = 0.74; 95% CI, 0.55–1.00 and 2.9% absolute risk reduction (6.3% vs. 9.2%)]. There were reductions across age, race, and family history. One placebo-controlled trial of men considered at greater risk for prostate cancer based on age, elevated PSA and previous suspicion of prostate cancer leading to a prostate biopsy reported that dutasteride did not reduce prostate cancers detected for cause based on needle biopsy but did reduce risk of overall incident prostate cancer detected by biopsy by 23% [RR = 0.77; 95% CI, 0.7–0.85 and absolute risk reduction 16.1% vs. 20.8%]. There were reductions across age, family history of prostate cancer, PSA level, and prostate volume subgroups. The Cochrane review defined ‘for-cause' cancers as:
- Suspected clinically from symptoms, abnormal digital rectal exam (DRE), or PSA and confirmed on biopsy.
- Study protocol recommended biopsy, but it was not done and the end of study biopsy showed prostate cancer.
- The end of study biopsy with PSA less than 4 ng/mL and/or suspicious DRE showed prostate cancer.