5-Alpha Reductase Inhibitors in Prostate Cancer: From Clinical Trials to Clinical Practice
May 2013
in “
European Urology
”
5-alpha reductase inhibitors 5-ARIs finasteride dutasteride prostate cancer PCa primary prevention secondary prevention pathologic progression therapeutic progression placebo PSA progression biochemical failure definitive therapy relative risk reduction PSA doubling hormonal therapy biochemical recurrence Propecia Avodart PSA
TLDR 5-Alpha reductase inhibitors may prevent prostate cancer but are not widely used due to concerns about trial relevance and potential risks, and more research is needed to confirm long-term benefits.
The document discusses the role of 5-alpha reductase inhibitors (5-ARIs), specifically finasteride and dutasteride, in the prevention and treatment of prostate cancer (PCa). Despite evidence of clinical efficacy, 5-ARIs have not been widely accepted in clinical practice. Landmark trials have shown that these drugs can prevent PCa, with finasteride and dutasteride demonstrating advantages in primary prevention. In secondary prevention, dutasteride reduced the time to pathologic or therapeutic progression by 38.9% compared to placebo. However, these results are controversial due to concerns about the generalizability of the trials and the end points used, such as mandatory end-of-study biopsies and the increased risk of high-grade disease. The document also describes a randomized controlled trial by Schröder et al., which found that dutasteride significantly delayed PSA progression and disease progression in patients with biochemical failure after definitive therapy. Out of 294 men enrolled, 187 completed the 24-month treatment, and dutasteride led to a 66.1% relative risk reduction in time to PSA doubling compared to placebo. However, the study's secondary end point was primarily based on PSA measurements, and the duration of the study was insufficient to demonstrate an impact on survival or delay in bone metastases. The document concludes that while there is potential for 5-ARIs to be effective earlier in the clinical spectrum of advanced PCa, the long-term benefits and harms of hormonal therapy in this setting are unclear, and more studies with objective survival end points are needed before recommending 5-ARI therapy for men with biochemical recurrence after definitive therapy.
