The REDUCE trial (Reduction by Dutasteride of Prostate Cancer Events) was a landmark randomized, double-blind, placebo-controlled trial of 8,231 men over 4 years that tested whether dutasteride could prevent prostate cancer. It demonstrated a 22.8% relative reduction in prostate cancer detection. Gleason 7-10 tumors were no more common on dutasteride (220 of 3,299 men versus 233 of 3,407 on placebo, P=0.81), but during years 3 and 4 there were 12 Gleason 8-10 tumors on dutasteride against 1 on placebo (P=0.003). That imbalance is why the FDA did not approve dutasteride for cancer prevention, and it remains debated.
Study Design
- Participants: 8,231 men aged 50-75 with elevated PSA (2.5-10 ng/mL) but negative biopsy
- Intervention: Dutasteride 0.5 mg daily vs placebo for 4 years
- Primary endpoint: Prostate cancer detection on protocol-mandated biopsies
Key Findings
- 22.8% relative risk reduction in prostate cancer detection with dutasteride (p<0.001)
- Cancer detected in 659 of 3,305 men on dutasteride (19.9%) versus 858 of 3,424 on placebo (25.1%), an absolute difference of 5.2 percentage points
- No significant difference in Gleason 7-10 tumors: 220 of 3,299 on dutasteride versus 233 of 3,407 on placebo (P=0.81)
- In years 3 and 4, 12 Gleason 8-10 tumors on dutasteride versus 1 on placebo (P=0.003). This, not the Gleason 7-10 count, is the actual high-grade signal
- Acute urinary retention fell from 6.7% on placebo to 1.6% on dutasteride, a 77.3% relative reduction
- Composite cardiac failure was more common on dutasteride (0.7%, 30 men) than placebo (0.4%, 16 men), P=0.03
The High-Grade Cancer Controversy
The years 3-4 excess of Gleason 8-10 tumors was the central finding that prevented FDA approval of dutasteride for prostate cancer prevention. Subsequent analyses have suggested it may be an artifact of detection bias: dutasteride shrinks the prostate, making biopsies more sensitive for detecting existing high-grade cancers rather than causing them. This remains an active area of debate. Prostate cancer prevention.
Sources
- Andriole GL, Bostwick DG, Brawley OW, et al. Effect of dutasteride on the risk of prostate cancer. N Engl J Med. 2010;362(13):1192-202. PubMed 20357281