The NCCN guidelines provide prognostic guidance and treatment options for patients (pts) with localized prostate cancer. Men with poor prognosis are considered high risk (HR) (clinical stage !T3a or PSA >20 ng/mL or Gleason (Gl) !8) and men with locally advanced disease (T3b-T4) or the worst prognosis (!2 HR factors) are considered very high risk (VHR). The 2015 guidelines expanded VHR by adding 2 new risk factors (RF) (primary Gl 5 or !5 cores with Gl 8-10) that better select pts at risk for poor outcomes after surgery. We reviewed treatment outcomes and patterns of failure in a cohort of HR pts to determine if the original or revised NCCN VHR groups offer prognostic information for pts treated uniformly with contemporary radiation therapy (RT) and androgen deprivation therapy (ADT). Materials/Methods: Two hundred three HR pts were extracted from an IRB approved database treated with RT from November 2001 to March 2012. Treatment was conformal RT to the prostate (78-82 Gy), pelvic lymph nodes (46-50 Gy), and ADT (6 months-2years). The HR cohort was divided into separate HR/VHR groupings based on the 2014 and 2015 NCCN definitions of VHR and since inclusion of !2 HR factors is optional we have 4 groups: VHR 2014 !T3b or AE !2 HR factors; and VHR 2015 !T3b or primary Gl 5 or !5 cores with Gl 8-10 or AE !2 HR factors. Outcomes for each of the 4 HR/VHR groups were compared. Disease-free survival (DFS) included metastatic, nodal, local, and biochemical failures (Phoenix definition). Kaplan Meyer (KM) method was used to determine probability of survival. Cox univariate and multivariate regression analysis were used to determine significant covariates. P values .05 were considered significant. Results: The 2015 NCCN revision increased the number of RFs considered for inclusion into the VHR group from 1-4. Pts were shifted from HR to VHR as follows: 2014 AE !2 HR factors (HR166:VHR37, HR131:VHR72) respectively and 2015 AE !2 HR factors (HR100:VHR103, HR65:VHR138) respectively. The percentage of VHR pts increased from 18% to 68% and the percentage of HR pts decreased from 82% to 32%. For all 203 pts: Median follow-up was 50 months; 30 of 203 (15%) experienced failure; median time to failure was 30 months; KM estimate of 4-year DFS was 87% (95% CI: 82%-92%) with no significant differences between the HR and vHR groups (log-rank PZns). On multivariate analysis the factors defining the VHR cohort defined by 2014 or 2015 criteria were not significant and only PSA !40 ng/mL was significant HR: 4.28, (95% CI: 1.98-9.25, P<.001, 4-year DFS 91% versus 68% PSA < 40 ng/mL: PSA ! 40 ng/mL). Conclusion: In this cohort treated with high-dose conformal RT and ADT, reclassification of pts into VHR groups using 2014 or 2015 criteria or upstaging pts with !2 HR criteria had no impact on treatment outcomes. Only PSA !40 ng/mL was associated with poor outcome on multivariate analysis. Further study and longer follow-up is required to validate these findings.

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