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Battling prostate cancer with 5-alpha-reductase inhibitors: a pyrrhic victory?
Richard M Hoffman1, Richard G Roberts, Michael J Barry
1Medicine Service, New Mexico VA Health Care System, Albuquerque, NM 87108, USA. rhoffman@unm.edu
Abstract:
Given the relatively small impact of prostate cancer screening on cancer mortality, experts are now suggesting that chemoprevention with 5-alpha-reductase inhibitors (5-ARI) may be a more effective strategy for cancer control. Two large placebo-controlled randomized trials found that men receiving 5-ARI were about 25% less likely than controls to be detected with cancer. However, most cancers were detected on routine biopsies required by study protocols. The benefit from receiving 5-ARI was minimal among men who underwent biopsy for clinical indications. Additionally, men receiving 5-ARI were more likely than controls to be diagnosed with high-grade cancers, though post-hoc analyses adjusting for biases accounted for the excess risk in one of the studies. A recent guideline recommended that men considering prostate cancer screening also consider chemoprevention. The rationale is that reducing cancer incidence, given the known risks for overdiagnosis and subsequent overtreatment, is sufficient justification for chemoprevention. However, a large randomized controlled trial found that screening was associated with a 70% increase in prostate cancer diagnosis--which chemoprevention would then reduce by 25%. This does not seem an acceptable trade-off especially because the potential increased risk for high-grade cancers could lead to higher cancer mortality.
Insights
Chemoprevention with 5-alpha-reductase inhibitors (5-ARI) may reduce prostate cancer detection by 25%. However, this benefit is minimal for clinically detected cancers and may increase high-grade diagnoses, potentially raising mortality risks.
Area of Science:
- Oncology
- Preventive Medicine
- Urology
Background:
- Prostate cancer screening has limited impact on mortality.
- Chemoprevention with 5-alpha-reductase inhibitors (5-ARI) is proposed as a more effective cancer control strategy.
- Concerns exist regarding overdiagnosis and overtreatment in prostate cancer.
Purpose of the Study:
- To evaluate the effectiveness of 5-ARI chemoprevention in reducing prostate cancer detection.
- To assess the impact of 5-ARI on cancer grade and potential mortality risks.
- To inform guidelines on prostate cancer screening and chemoprevention strategies.
Main Methods:
- Analysis of two large placebo-controlled randomized trials on 5-ARI use.
- Examination of cancer detection rates based on routine biopsies versus clinical indications.
- Post-hoc analyses to adjust for biases in high-grade cancer diagnoses.
Main Results:
- Men receiving 5-ARI showed a 25% reduction in cancer detection compared to controls.
- The benefit of 5-ARI was minimal in men with clinically indicated biopsies.
- An increased risk of high-grade cancer diagnosis was observed in men taking 5-ARI, though some biases were accounted for.
Conclusions:
- While 5-ARI may reduce prostate cancer incidence, its clinical benefit is questionable, especially for clinically detected cancers.
- The potential increase in high-grade diagnoses necessitates careful consideration due to possible elevated cancer mortality.
- Integrating chemoprevention with screening requires a thorough risk-benefit assessment.
