The Role of Prostate-specific Antigen Persistence After Radical Prostatectomy for the Prediction of Clinical Progression and Cancer-specific Mortality in Node-positive Prostate Cancer Patients

A complete biochemical response (BR) immediately after surgery could be considered an indicator of optimal cancer control after radical prostatectomy (RP). OBJECTIVE: To evaluate the prognostic value of early postoperative prostate-specific antigen (PSA) levels after RP in patients with lymph node invasion (LNI). DESIGN, SETTING, AND PARTICIPANTS: The study included 319 prostate cancer patients with LNI who were treated with RP and extended pelvic lymph node dissection (ePLND) at a single institution between 1998 and 2013. All men had complete clinical, pathologic, and follow-up data, including PSA value at 6 wk after surgery. Patients were divided into two groups according to PSA value at 6 wk after surgery: complete BR (PSA <0.1 ng/ml) and PSA persistence (PSA ≥0.1 ng/ml). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier analyses were used to assess 8-yr clinical recurrence (CR) and cancer-specific mortality (CSM) rates according to PSA persistence after RP. Multivariable Cox regression analysis was used to test the association between PSA persistence and CR. Covariates consisted of pathologic Gleason score (≤7 vs ≥8), number of positive nodes, surgical margins status (negative vs positive), and adjuvant therapies (none vs androgen deprivation therapy (ADT) vs adjuvant radiotherapy plus ADT). When we performed multivariable analyses assessing the association between PSA persistence and CSM pathologic Gleason score represented the only covariate due to the low number of events (n=13). RESULTS AND LIMITATIONS: Overall, 83 patients (26%) had PSA persistence. Men with PSA persistence had higher 8-yr CR and CSM rates than those with complete BR (69% vs 12% and 16% vs 4.2%, respectively; all p≤0.002). This was confirmed in multivariable analyses, where PSA persistence at 6 wk after surgery was an independent predictor of both CR (hazard ratio [HR]: 8.3; 95% confidence interval [CI], 4.73-14.7; p≤0.001) and CSM (HR: 2.16; 95% CI, 1.63-2.86; p≤0.001). Pathologic stage lower than pT3a, biopsy and pathologic Gleason score ≥8, positive surgical margins, and three or more positive lymph nodes were significantly associated with PSA persistence (all p≤0.04). Our study is limited by its retrospective design. CONCLUSIONS: Early BR can be achieved in approximately 75% of men with LNI submitted to RP and ePLND. PSA assessment early after surgery has an important prognostic role in the prediction of CR and CSM in node-positive patients. A risk stratification of these patients based on PSA persistence could guide physicians to properly select patients who may benefit the most from timely multimodal treatments. PATIENT SUMMARY: The risk of clinical recurrence and cancer-specific mortality is heterogeneous in patients with prostate cancer with lymph node invasion. Node-positive patients with complete biochemical response early after surgery share more favorable oncologic outcomes than those with PSA persistence. These results are important to plan the optimal postoperative patient management.