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Purpose Studies comparing radical prostatectomy (RP) outcomes with those of radiotherapy with or without androgen deprivation therapy (RT±ADT) for prostate cancer (PCa) have yielded conflicting results. Therefore, we used propensity score-matched analysis and competing risk regression analysis to compare cancer-specific mortality (CSM) and other-cause mortality (OCM) between these two treatments. Materials and Methods The multi-center, Severance Urological Oncology Group registry was utilized to identify 3,028 patients with clinically localized or locally advanced PCa treated by RP (n=2,521) or RT±ADT (n=507) between 2000 and 2016. RT±ADT cases (n=339) were matched with an equal number of RP cases by propensity scoring based on age, preoperative prostate-specific antigen, clinical tumor stage, biopsy Gleason score, and Charlson Comorbidity Index (CCI). CSM and OCM were co-primary endpoints. Results Median follow-up was 65.0 months. Five-year overall survival rates for patients treated with RP and RT±ADT were 94.7% and 92.0%, respectively (p=0.105). Cumulative incidence estimates revealed comparable CSM rates following both treatments within all National Comprehensive Cancer Network risk groups. Gleason score ! 8 was associated with higher risk of CSM (p=0.009). OCM rates were comparable between both groups in the low- and intermediate-risk categories (p=0.354 and p=0.643, respectively). For high-risk patients, RT±ADT resulted in higher OCM rates than RP (p=0.011). Predictors of OCM were age ! 75 years (p=0.002) and CCI ! 2 (p < 0.001). Conclusion RP and RT±ADT provide comparable CSM outcomes in patients with localized or locally advanced PCa. The risk of OCM may be higher for older high-risk patients with significant comorbidities.

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