Radiation therapy after radical prostatectomy is associated with higher other-cause mortality

Purpose To test the association between external beam radiotherapy (EBRT) after radical prostatectomy (RP) vs RP only on rates of other-cause mortality (OCM) in men with prostate cancer (PCa). Patients and methods Within the 2004-2016 Surveillance, Epidemiology, and End Results database, we identified 181,849 localized PCa patients, of whom 168,041 received RP only vs 13,808 who received RP + EBRT. Cumulative incidence plots displayed OCM between RP vs RP + EBRT after propensity score matching for age, PSA, clinical T- and N-stages, and biopsy Gleason scores. Multivariable competing risks regression models addressed OCM, accounting prostate cancer-specific mortality (CSM) as a competing event. Stratifications were made according to low- vs intermediate- vs high-risk groups and additionally according to age groups of <= 60, 61-70, and >= 71 years, within each risk group. Results In low-, intermediate-, and high-risk patients, RP + EBRT rates were 2.7, 5.4 and 17.0%, respectively. After matching, 10-year OCM rates between RP and RP + EBRT were 7.7 vs 16.2% in low-, 9.4 vs 13.6% in intermediate-, and 11.4 vs 13.5% in high-risk patients (all p < 0.001), which, respectively, resulted in multivariable HR of 2.1, 1.3, and 1.2 (all p < 0.001). In subgroup analyses, excess OCM was recorded in low-risk RP + EBRT patients of all age groups (all p <= 0.03), but only in the older age group in intermediate-risk patients (61-70 years, p = 0.03) and finally, only in the oldest age group in high-risk patients (>= 71 years, p = 0.02). Conclusion Excess OCM was recorded in patients exposed to RT after RP. Its extent was most pronounced in low-risk patients, decreased in intermediate-risk patients, and was lowest in high-risk patients.