External beam radiation treatment of prostate cancer increases rectal cancer risk

Background: Prostate cancer (PC), the most common invasive cancer among US men, claimed 28,170 lives in 2012. Most PCs are organ-confined at diagnosis and are candidates for external-beam radiation therapy (EBRT) or prostatectomy (SURG). We assessed whether EBRT for PC, that exposes peri-rectal tissue, was followed by increased risk of rectal cancer, relative to SURG. Methods: Record linkage for all 337,992 new organ-confined PCs and 55,724 male rectal cancers in California (1988-2010) identified men diagnosed with rectal cancer more than five years following PC treatment with EBRT or SURG. Among men treated exclusively with EBRT versus SURG, the Cox proportional hazards ratio (HR) for subsequent rectal cancer was assessed. Demographic covariates included: age (<50, 50-74 & 75+ years), race/ethnicity as Asian-Other (A-O), non-Hispanic black (NHB), Hispanic (Hisp) and NH white (NHW), socioeconomic status quintiles (1-5 Highest) and diagnosis year. Results: Among 42,940 PC cases treated with EBRT, 194 were later diagnosed with rectal cancer, compared to 254 subsequent rectal cancers among 68,851 PC cases treated with SURG. Adjusting for demographic covariates and PC diagnosis year, the rectal cancer hazards ratio contrasting EBRT versus SURG was 1.62 with 95% confidence interval limits (95% CI) of 1.33-1.99. Year of diagnosis persisted as a significant predictor of rectal cancer hazards in the full model (HR=0.94; 95% CI=0.91-0.96), while no other covariate prevailed. Conclusions: Findings reveal increased rectal cancer hazards among organ-confined prostate cancer patients treated with EBRT, relative SURG that is independent of covariates. Further analyses seeking to distinguish roles of EBRT delivery modalities and dose are ongoing.