Dutasteride and Prostate Cancer Risk: Does Family History of Prostate and/or Breast Cancers Influence the Number Needed to Treat? Results from REDUCE

Purpose: In REDUCE, dutasteride was associated with a ~5% absolute reduction in the risk of biopsydetected prostate cancer (PCa). Material and methods: We tested the influence of family history on the association between dutasteride and PCa diagnosis and calculated the number needed to treat (NNT) with dutasteride to avoid one PCa diagnosis. The REDUCE trial tested dutasteride 0.5mg/day for PCa risk reduction in men aged 50-75 with a serum PSA of 2.5-10.0ng/mL and a negative biopsy. Among men who underwent >1 on-study biopsy with complete data (n=6,415; 78.1%), the association between dutasteride and PCa risk as a function of PCa and/or breast cancer (BCa) family history was examined using multivariable logistic regression. Absolute risk reduction (ARR) and NNT were calculated. Results: On multivariate analysis, dutasteride was significantly associated with lower PCa risk in men without family history (25% lower; p<0.001), PCa family history only (37% lower; p=0.009), or BCa family history only (38% lower; p=0.04). While dutasteride lowered PCa risk in men with both PCa and BCa family history by 15%, this was not significant (p=0.69), though the number of men was small (n=115). ARRs were 6-9% for men with a PCa and/or BCa family history vs. 5% in men with no family history which translated into NNTs of 11-16 in men with PCa and/or BCa family history vs. 21 for men without family history. Conclusion: Using dutasteride as a model of chemoprevention, therapies targeting individuals with specific family histories may improve the risk-benefit profile. However, future studies are warranted to confirm our