An analysis of the time course of postoperative prostate-specific antigen failure in patients with positive surgical margins: implications on the use of adjuvant therapy.

ABSTRACT

OBJECTIVES: The role of adjuvant therapy in the postprostatectomy setting for positive margin patients is an unresolved issue. The purpose of this study is to provide the rationale for patient selection in Phase III trials that test the impact of adjuvant therapy on survival in positive margin prostate cancer patients. METHODS: Early (12 months or less) and delayed (more than 12 months) postoperative prostate-specific antigen (PSA) failure have been correlated with distant and local failure, respectively, as the site of first failure. In this study, a Cox regression multivariate analysis was used to determine the significant independent clinical and pathologic predictors of early and delayed postoperative PSA failure in 143 margin-positive prostate cancer patients. RESULTS: Margin-positive patients with positive pelvic lymph nodes, seminal vesicle invasion, or prostatectomy Gleason sum 8 or higher were excluded. For the remaining patients, a prostatectomy Gleason sum of 7, preoperative PSA more than 20 ng/mL, and an endorectal coil magnetic resonance imaging (erMRI) scan showing extensive disease were significant independent predictors of early postoperative PSA failure. Conversely, a prostatectomy Gleason sum of 6 or less, preoperative PSA 20 ng/mL or less, and an erMRI showing limited disease predicted delayed PSA failure. CONCLUSIONS: Preliminary data suggest that the pattern of first failure can be predicted by the time course of rise in the postoperative PSA. The preliminary results of this study suggest that patient selection for clinical trials examining the efficacy of postoperative adjuvant therapy in the positive margin patient may be determined on the basis of the clinical and pathologic characteristics that predict early versus delayed postoperative PSA failure.