To compare cancer specific mortality (CSM) rates between radical prostatectomy (RP) vs. external beam radiotherapy (EBRT) in National Comprehensive Cancer Network (NCCN) high risk (HR) patients, as well as in Johns Hopkins University (JH) high-risk (HR) and very high risk (VHR) subgroups.

Within the Surveillance, Epidemiology, and End Results database (2010-2016), we identified 24,407 NCCN HR patients, of whom 10,300 (42%) vs 14,107 (58%) patients that qualified for JH HR and VHR, respectively. Overall, 9,823 (40%) underwent RP vs 14,584 (60%) EBRT. Cumulative incidence plots and competing-risks regression addressed CSM after 1:1 propensity score matching (according to age, PSA, clinical T and N stages and biopsy Gleason score) between RP and EBRT patients. All analyses addressed the combined NCCN HR cohort, as well as in JH HR and JH VHR subgroups.

In the combined NCCN HR cohort, 5-year CSM rates were 2.3% for RP vs 4.1% for EBRT and yielded a multivariate hazard ratio (HR) of 0.68, 95% confidence interval (CI) (0.54-0.86, p <0.001) favoring RP. In VHR patients 5-year CSM rates were 3.5% for RP vs 6.0% for EBRT, yielding a multivariate HR of 0.58 (95% CI 0.44-0.77, p <0.001) favoring RP. Conversely, in HR patients, no significant difference was recorded between RP vs EBRT (HR 0.7, 95% CI 0.39-1.25, p=0.2).

Our data suggests that RP holds a CSM advantage over EBRT in the combined NCCN HR cohort, and in its subgroup of JH VHR patients.