Background: Objectives were to1) identify predictors of biochemical failure(BCF) -free survival (FFS) & distant metastases free-survival (DMFS) in high-risk prostate cancer (HRPC) patients treated with external beam radiotherapy (EBRT) with or without androgen deprivation therapy (ADT); 2) assess the impact of nodal irradiation & escalation of dose to the nodal volumes in HRPC. Methods: Between Feb 2000 & May 2011, 462 patients with HRPC were treated with EBRT +/- ADT. This spanned an era of technical development; prior to 2002 conventional dose radiotherapy was routinely delivered, between 2002-2008, dose escalation to the prostate & pelvic lymph nodes was undertaken in a phase II trial & subsequently all patients were treated with a dose-escalated protocol. The disease characteristics included, a median PSA of 20ng/ml (range: 1-563), T3-T4 in 33% (n=158), & Gleason grade group (GGG) 3-5 in 72% (n=331). The majority (n=405, 88%) received ADT with EBRT & median duration of ADT was 36 months (range: 0-197). Dose escalated EBRT was utilized in 52% (n=241) & nodal irradiation in 69% (n=317); escalation of dose to nodal volumes was performed in 20% (n=93). Results: The median follow-up was 8.7yrs (range: 0.9-18.9). Median nadir PSA was < 0.05ng/ml (range: <0.05-5.78) with median time to nadir (TTN) of 11 months (range: 2-130). Cumulative incidence rates of BCF at 5 and 10-yrs were 23% & 45%; corresponding rates for DM were 6.6% & 14%, respectively. The 5 & 10-yr FFS rates were 75% & 51%; corresponding DMFS rates were 91.5% & 80%, respectively. On multivariate analysis, T stage (p<0.001), GGG (p<0.001), ADT (p=0.002), dose escalation to prostate (P=0.012) & median nadir PSA (p<0.001) were independent predictors of FFS. The GGG (p=0.007), median nadir PSA (p=<0.001) & Nodal RT (p=0.03) were independent predictors of DMFS. PSA of 20 & TTN predicted neither FFS nor DMFS. Conclusions: Nadir PSA level was an independent predictor of FFS & DMFS. Undetectable PSA level was associated with prolonged FFS & DMFS. Dose escalation to prostate resulted in an improved FFS & Nodal irradiation in an improved DMFS. Further studies are required to identify subgroups that may benefit the most from nodal irradiation.