Purpose: The cohort of patients with locally advanced prostate cancer (PC) and positive surgical margin(s) at radical prostatectomy (RP) who would benefit from salvage or adjuvant treatment is unclear. This study examines the risk of prostate-specific antigen (PSA) relapse in a large population of men with PC after margin-positive RP. Methods and Materials: Using a multi-institutional database, patients with clinically localized PC who underwent RP between 2002 and 2010 with recorded follow-up PSA were retrospectively selected. Patients were excluded for pathologic seminal vesicle or lymph node involvement, metastatic disease, pre-RP PSA ≥ 30, or adjuvant (nonsalvage) radiation therapy or hormone therapy. The primary endpoint was biochemical relapse free survival (bRFS), where PSA failure was defined as PSA > 0.10 ng/mL and rising, or at salvage intervention. The Kaplan-Meier method was employed for bRFS estimates; recursive partitioning analysis using cumulative or single maximal margin extent (ME) and Gleason grade (GG) at RP was applied to identify variables associated with bRFS. Results: At median follow-up of 105 months, 210 patients with positive margins at RP were eligible for analysis, and 89 had experienced PSA relapse. Median age was 61 years (range, 43-76), and median pre-RP PSA 5.8 ng/mL (1.6-26.0). Recursive partitioning analysis yielded 5 discrete risk groups, with the lowest risk group (GG1, ≤ 2 mm ME) demonstrating a bRFS of 92% at 8 years compared with the highest risk group (GG3-5, ≥ 3 mm ME) of 11%. Conclusions: This retrospective study suggests that it may be possible to risk-stratify patients undergoing margin-positive RP using commonly acquired clinical and pathologic variables. Patients with low-grade tumors and minimally involved margins have a very low recurrence risk and may be able to forego postprostatectomy radiation. Meanwhile, those with higher grade and greater involvement could benefit from adjuvant or early salvage radiation therapy.

105 Background: Though an involved margin at prostatectomy has been associated with elevated rates of PSA relapse, there has been an absence of consensus regarding the risk of relapse specific to the site(s) of margin involvement. Specifically, the apical margin has been sometimes considered "lower risk," based upon historical series. The present study seeks to determine the rate of PSA relapse in patients who had undergone prostatectomy with involved surgical margin, without immediate post-operative (adjuvant) therapy, with comparison of relapse rates by site of involved margin. Methods: A retrospective database review was performed, including patients with clinically localized prostate cancer and pre-operative PSA <30, who had undergone prostatectomy, with site(s) of involved margin characterized. Slides were re-reviewed by a pathologist for verification of site of margin involvement. Patients were excluded if seminal vesicle invasion or lymph node involvement was noted in the surgical specimen, if any adjuvant therapy was delivered prior to relapse, or if post-operative follow-up with PSA was <12 months. Relapse was defined as >0.2 and rising after prostatectomy. Log-rank analysis was employed for comparison of disease control between groups; the Kaplan-Meier method was employed to construct survival curves and estimate 5-year disease control. Results: Between 2002 and 2010, 155 patients were identified for inclusion in the present analysis. Of these, 105, 37, and 7 patients had 1, 2, and >2 sites of margin involvement, respectively. The apex was the sole site of margin involvement for 70 patients. At a median follow-up of 68 months (range 22-145), 62 patients (40%) had experienced PSA relapse. There was no statistically significant difference in risk of PSA relapse by site of margin involvement or number of foci of margin involvement. The 5-year estimates for PSA relapse for margin involvement of the apex only, other site only, or both were 40.5%, 33%, and 49.1%, respectively. Conclusions: Involvement of the apical margin is associated with a high rate of early PSA relapse, similar to rates noted when other site(s) of margin involvement are noted.

131 Background: An involved surgical margin at prostatectomy has long been associated with elevated risk of prostate cancer recurrence; however, not all patients with an involved margin will relapse, and thus details of the involved margin may provide an opportunity for risk subset stratification. The present investigation seeks to determine whether a difference exists in recurrence rates when the margin involvement is at a site of prostate capsule invasion versus within the prostate parenchyma proper. Methods: Patients were retrospectively identified for inclusion by clinically localized disease and PSA <30 at diagnosis, managed with prostatectomy alone and identified to have involvement of surgical margin(s). Exclusion criteria were: pT3b or pN1 disease, immediate/non-salvage post-operative radiation or hormone therapy, or insufficient follow-up (<12 months). Pathology slides were reviewed by a pathologist blinded to outcome, for determination of capsule invasion at a site of margin involvement. Disease recurrence was defined as PSA >0.2 and rising, per contemporary guidelines. Kaplan-Meier method was employed for disease control estimates. Results: Between 2003 and 2010, 155 patients were identified for inclusion in the present study. The median age was 61 years, and all had cT1-2 disease (75% T1c). At diagnosis, the Gleason score was 6, 7, and 8-9 for 103 (66%), 42 (27%), and 10 (6%) patients, respectively, with median PSA 5.6 (85% <10). For 149 patients with reviewable margin site data, 51 (34%) demonstrated involvement within or beyond the capsule. At a median follow-up of 68 months (range 13-137), 62 patients had experienced PSA relapse. The estimated 5-year PSA relapse rates for patients with an involved margin at the site of capsule invasion versus prostate parenchyma were 49% versus 34%, respectively (p=0.015). Conclusions: Early PSA relapse rates for all patients with involved surgical margin(s) but negative seminal vesicles and nodes at prostatectomy are high; however, for patients who are followed without immediate adjuvant therapy, presence of tumor cells at the margin in a site of capsule invasion or penetration confers a higher risk of recurrence.

PURPOSE:To determine whether additional pathology details may provide risk stratification for patients with involved surgical margins at radical prostatectomy (RP). METHODS AND MATERIALS:Eligible patients underwent RP between 2003 and 2010. Patients with preoperative prostate-specific antigen (PSA) ≥20, follow-up <12 months, lymph node or seminal vesicle involvement, or who received radiation therapy or hormone therapy prior to PSA relapse were excluded. Surgical specimens were reviewed by a study pathologist, blinded to outcomes. Survival analysis methods were employed to assess disease control and survival rates, as well as association of patient-, tumor-, and treatment-specific factors for endpoints. RESULTS:Of 355 RP cases, 279 patients were eligible for the present analysis. At a median follow-up of 53 months (range, 16-127), 31/114 (27%) of patients with involved surgical margins experienced PSA relapse, as compared with 7/165 (4%) for negative margins (hazard ratio, 4.997; 95% confidence interval, 2.425-10.296; P < .0001). Detailed pathology review demonstrated associations between PSA relapse and Gleason score at RP, extent of margin involvement (width), capsule penetration, and perineural invasion. Subgroup analysis identified low risk (4%) of 5-year PSA relapse for patients with Gleason ≤6 mm and margin width ≤4 mm (single maximal or cumulative). All subgroups with higher Gleason score or wider margin were associated with >20% risk of PSA relapse at 5 years. CONCLUSIONS:Within the present study, Gleason score, 6 patients with margin width ≤4 mm appear to have low rates of early PSA relapse following RP. Low-grade cases with larger extent of margin involvement or higher risk Gleason score patients with any margin involvement have high rates of early PSA relapse.

215 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. [Table: see text]

Background and objectiveThe optimal primary intervention for treatment of clinically localized high-grade prostate adenocarcinoma remains to be identified.The present investigation reports disease control and survival outcomes in patients treated with primary radical prostatectomy.Methods Eligible patients were diagnosed with Gleason score 8-10 at diagnostic biopsy and prostate-specific antigen (PSA) Ͻ 30 ng/mL, treated with primary radical prostatectomy, without clinical evidence of distant metastatic disease, seminal vesicle invasion, or lymph node involvement.Demographic, treatment, and outcome data were retrospectively collected and analyzed from a clinical database.Survival analysis methods were employed to assess disease control and survival rates, as well as association of patient-, tumor-, and treatment-specific factors for endpoints. ResultsFifty patients were eligible for the present analysis, with Gleason 8 and 9 in 32 (64%) and 18 (36%) patients, respectively.Surgical margin, seminal vesicle, and lymph node involvement were noted 32 (64%), 18 (36%), and 6 (12%) patients, respectively; only 4 (8%) received adjuvant radiotherapy.At a median follow-up of 44.9 months (range, 4.2-104.6),33 patients (66%) had experienced PSA relapse, of whom 7 have been successfully salvaged.Four patients died, all with uncontrolled disease.The estimated 5-year freedom from failure was 17%.Interval from biopsy to prostatectomy, surgical margin status, and seminal vesicle involvement were associated with decreased overall survival.Conclusions High-risk Gleason score at biopsy is associated with suboptimal PSA control at 5 years following prostatectomy alone; however, in the setting of uninvolved seminal vesicles and lymph nodes, the dominant pattern of failure appears to be local, and early postoperative radiotherapy should be considered.