Background: EPE is an established risk factor for PSA failure following RP; however, often this is identified in the context of other high-risk feature(s). The objective of the current investigation study is to describe the PSA relapse rate for patients with confirmed EPE and identify associated factors for risk stratification. Methods: Retrospective analysis of patient- and tumor-specific factors. Eligible patients underwent RP for biopsy-proven prostate adenocarcinoma and pathologic finding of EPE. Patients with PSA >30 at diagnosis, involved seminal vesicles or lymph nodes at RP, or who received adjuvant therapy (hormone or radiation) were excluded. Results: Between 2002 and 2010, 644 patients underwent RP, of whom 95 had EPE and were eligible per above. The median age at diagnosis was 64 years (range 44-74), and pre-RP PSA 6.1 (1.8-25.4). At a median PSA follow-up of 64 months (range 13.3-136.5), 38 patients had experienced PSA relapse at a median of 18 months post-RP (1.2-129.8), of whom 28 had involved surgical margins. For the entire population, PSA relapse at 5 years was 39.2% (95% CI, 38.1-40.3%). Factors associated with PSA relapse included pre- and post-RP PSA and Gleason score (GS), and margin status. Subset evaluation by RP Gleason score and margin status is demonstrated in the table. Conclusions: Within the present study, all patients with EPE appear to have elevated rates of PSA relapse within 5 years of RP. Longer follow-up is necessary to determine whether the low-risk group may be safely observed following margin-negative RP. Low-grade EPE cases with involved margin and/or higher-risk Gleason score patients with any EPE/margin involvement have high rates of early PSA relapse, and should be recommended early post-operative (adjuvant) therapy in order to optimize PSA control.