BackgroundOptimal treatment of high-risk prostate cancer remains controversial. We aimed to compare treatment outcomes of prostate cancer patients treated with definitive external-beam radiotherapy (ExRT) or radical prostatectomy (RP).MethodsThe records of 120 high-risk clinical stage T2b-T4N0M0 prostate cancer patients treated with definitive ExRT or RP were reviewed. Patients with pretreatment prostate-specific antigen (PSA) levels 20ng/mL or clinical T3 stage or Gleason score (GS) 8 were included in the study. Biochemical failure free survival (BFFS), distant metastasis free survival (DMFS), cancer-specific survival (CSS) and overall survival (OS) were analyzed. Cox regression analysis was performed to determine predictors of BF.ResultsSeventy-two patients received definitive ExRT with androgen-deprivation therapy in 95.8% and 48 patients underwent RP with pelvic lymph node dissection. Mean age (67.76.6 vs 64.5 +/- 7.6year, p=0.017) and the rate of patients with PSA levels 20ng/mL (69.4% vs 47.9%, p=0.022) were higher in the definitive ExRT group than the RP group. Distributions of GS and clinical T stage were similar. Mean follow-up was 60.2 +/- 30.3months in the definitive ExRT group and 41.3 +/- 21.5months in the RP group (p<0.001). Twenty-five % of the RP group received adjuvant ExRT and 41.7% received salvage ExRT. Biochemical failure was significantly higher (52.1% vs 21.4%, p<0.001) and the mean BFFS was significantly lesser (34.4 +/- 3.9 vs 97.8 +/- 5.9months, p<0.001) in the RP group than the definitive ExRT group. However, DMFS, CSS and OS were similar in both groups. In multivariate analysis, being in the RP group significantly increased the risk of BF (p<0.001). Furthermore, not receiving pelvic lymphatic irradiation in the definitive ExRT group (p=0.048) and having positive surgical margin in the RP group (p=0.050) increased the risk of BF.Conclusions BF was significantly higher and the mean BFFS was significantly lesser in high-risk prostate cancer patients undergoing RP than definitive ExRT while DMFS, CSS and OS were similar in both treatment groups.