Molecular markers that predict for recurrence in men with margin-positive localized prostate cancer.

Abstract

4650 Background: Men with positive margins after radical prostatectomy (RP) for localized prostate cancer (PC) have a 40-50% biochemical relapse rate. Adjuvant radiotherapy after RP improves biochemical progression-free survival in patients with positive surgical margins, extraprostatic extension (EPE) and/or seminal vesicle involvement (SVI) but is associated with a 5-fold increase in bladder and rectal toxicity. There is an urgent need to identify new prognostic markers to better define the group of patients who would benefit from multimodality therapy. Methods: Nuclear b-catenin, membranous secreted frizzled-related protein 4 (sFRP4), AZGP1 and macrophage inhibitory cytokine-1 (MIC-1) have previously been identified as molecular markers of outcome in localized PC by our group. From these previous studies, 186 localized PC cases had positive margins. Using Kaplan-Meier and Cox Proportional Hazards analyses, we assessed the association between these four molecular markers and biochemical relapse in men with margin-positive localized PC. Results: Among the published cohort of 330 men with localized prostate cancer, we identified 186 with positive margins post RP; 53% had preoperative PSA >10 ng/ml, 72% EPE, 24% SVI and 57% RP Gleason score ≥ 7. There were 67/186 (36%) men who received adjuvant therapy (46 hormonal treatment and 21 radiotherapy). Three of the four molecular markers predicted for biochemical relapse on univariate analysis: AZGP1 (p=0.009), membranous sFRP4 (p=0.03) and MIC-1 (p=0.04). Only absent or low AZGP1 expression (HR 2.2, 95% CI 1.2-4.0, p=0.01) was an independent predictor of recurrence in margin positive localized PC when modeled with preoperative PSA (HR 1.6, 95%CI 0.8-3.1, p=0.2), EPE (HR 1.5, 95%CI 0.7-3.3, p=0.2), SVI (HR 1.4, 95%CI 0.7-3.0, p=0.4), Gleason score ≥ 7 (HR 1.3, 95%CI 0.6-2.9, p=0.5) and adjuvant treatment (HR 1.4, 95%CI 0.7-2.6, p=0.4) in a multivariate analysis. Conclusions: AZGP1 is a potential molecular marker for biochemical relapse in men with localized PC and positive margins after RP. Routine assessment of this biomarker may lead to better selection of patients who will benefit from post-RP radiotherapy and avoid morbidity in men at less risk. No significant financial relationships to disclose.