Alexis Freeland and colleagues assessed a post-hoc analysis of the REDUCE clinical trial to determine whether compliance to biopsy recommendations influences prostate cancer risk. Specifically, the authors tested whether black race predicts prostate cancer risk, grade and biopsy compliance in the REDUCE cohort.
The authors identified 7,415 men (2.4% black, 97.6% white) with complete data from REDUCE, a 4 year, multicenter, double-blind, placebo-controlled randomized control trial testing dutasteride vs placebo on prostate cancer risk [1]. Eligible men were 50-75 years old, had a single, negative, pre-study biopsy with a PSA=2.5-10 [1]. Men were mandated to undergo a protocol-dependent biopsy at two and four years regardless of PSA; race was a self-reported covariate. Prostate cancer grade was classified as low (Gleason score < 7) or high (Gleason ≥ 7). Univariable and multivariable logistic and multinomial regression models were used to test if race predicts prostate cancer, grade (low vs high vs no prostate cancer) and biopsy compliance. Multivariable models were adjusted for age, PSA, BMI, DRE, prostate volume, region, treatment arm, prostate cancer family history and smoking.
Black and white men had similar age, prostate volume, treatment arm, smoking status and prostate cancer family history in the REDUCE trial. However, black men were more likely to have an abnormal DRE (8.4% vs 3.5%, p<0.001), lower pre-study PSA (5.7 vs 5.3 ng/mL, p=0.05) and were most likely to reside in North America (p<0.001). Black race was independently associated with lower risk of having any on-study (OR 0.53, 95%CI 0.38-0.74), two (OR 0.53, 95%CI 0.39-0.74) or four-year (OR 0.47, 95%CI 0.30-0.75) per protocol prostate biopsy (all p≤0.001). Among 1,393 men with prostate cancer, there were no differences in distribution between black (2.3%) and white men (97.7%, p=0.08). Additionally, there was no association between race and overall risk of prostate cancer or at four-year biopsy on univariable or multivariable analysis, however black race was associated with higher prostate cancer risk on two-year biopsy (multivariable analyses, OR 1.60, p=0.04). Black men had higher overall risk of high-grade prostate cancer (unadjusted RRR 1.76, p=0.05; adjusted RRR 1.91, p=0.03) and on two-year biopsy (unadjusted RRR 2.44, p=0.004; adjusted RRR 2.53, p=0.005).
The strength of this study is the post-hoc analysis design of an RCT mandating per-protocol biopsies allowing the ability to test compliance to prostate biopsy. A limitation of the study is the lack of racial heterogeneity considering that >97% of patients in REDUCE were a Caucasian race. The authors concluded with several important take-home messages from their study:
- Black men had greater non-compliance with study mandated biopsy
- While black men had greater prostate cancer risk (especially high-grade) on the two-year biopsy, this effect was lost overall due to lower compliance leading to less opportunity for prostate cancer detection
- If true, population-level estimates of excess prostate cancer burden in black men may underestimate the degree of prostate cancer disparity.
1. Andriole GL, Bostwick DG, Brawley OW, et al. Effect of dutasteride on the risk of prostate cancer. N Engl J Med 2010;362(13):1192-1202.
Presented by: Alexis Freedland, Cedars-Sinai Medical Center, Los Angeles, CA
Co-Authors: Lauren Howard, Durham, NC, Adriana Vidal, Los Angeles, CA, Daniel Moreira, Chicago, IL, Gerald Andriole, St Louis, MO, Ramiro Castro-Santamaria, Philadelphia, PA, Stephen Freedland, Los Angeles, CA
Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA