GETUG-AFU 22 Phase II Randomized Trial Evaluating Outcomes of Post-Operative Immediate Salvage Radiation Therapy with or without ADT for Patients with Persistently Elevated PSA Level

Abstract

<h3>Purpose/Objective(s)</h3> Radical prostatectomy (RP) is one of the recommended option for localized prostate cancer (PCa) treatment but no clear recommendations guide post-operative treatment patients with persistently elevated prostate-specific antigen (PSA) after RP. The aim of this trial was to compare immediate salvage radiation therapy (iSRT) with or without short-term androgen deprivation therapy (ADT) in these patients. <h3>Materials/Methods</h3> RP patients with nonmetastatic PCa on conventional preoperative imaging, and with a post-RP PSA level between 0.2 and 2 ng/mL were randomized (1:1) to iSRT alone (iSRT arm) or 6 months of ADT (degarelix) with iSRT (iSRT+ADT arm). ISRT consisted of pelvic irradiation (46 Gy in 23 Fr) with a boost on the prostate bed (66 Gy in 33 Fr). The primary endpoint was event-free survival (EFS). Biochemical progression-free survival (bPFS), metastates-free survival (MFS), overall survival (OS), quality of life, and toxicities were evaluated as secondary endpoints. <h3>Results</h3> From Jan-2013 to Sept-2015, 125 pts were included (iSRT arm: 64 pts; iSRT+ADT arm: 61). Median follow up was 75.0 months (95% CI: 74.1-76.6). The baseline characteristics were well-balanced between the two arms. Median PSA was 0.6 ng/mL (0.12-3.65) at randomization. All patients received the planned iSRT and 98.4% in the arm iSRT+ADT received ADT as planned. The efficacy results were analyzed at 5 years. EFS was 62.3% (95% CI: 48.9-73.2) in iSRT arm and 63.5% (95% CI: 49.9-74.2) in iSRT+ADT arm (HR=0.83; 95%CI: 0.47-1.47; p=0.528). bPFS was 62.3% (95% CI: 48.9-73.2) in iSRT arm and 66% (95% CI: 52.3-76.6) in iSRT+ADT arm (HR=0.76; 95%CI: 0.44-1.31; p=0.322). MFS was in favor of the iSRT+ADT arm with HR=0.51 (95% CI: 0.26-0.99; p=0.048). OS data were not mature at the time of analysis. Multivariate analysis demonstrated that PSA level <0.6 ng/ml at randomization and tumor ≤pT3a were associated with increased bPFS (HR=1.84; 95%CI: 1.02-3.33; p=0.05 and HR=2.96; 95%CI: 1.66-5.25; p=0.0002, respectively). PSA level <0.6 ng/ml at randomization was associated with improved MFS (HR=2.82; 95%CI: 1.14-6.95; p=0.019). No grade 4 toxicities were observed. Overall, no difference in acute toxicity were observed between the 2 arms and more late toxicities (≥6 months after iSRT) were observed in the iSRT+ADT than the iSRT arm (53.1% vs 70.5%; p=0.046). At 12 months ADT-related symptoms were more important in the iSRT+ADT arm (QLQ-PR25; p=0.04). At 24 months, no difference in QLQ-C30 or QLQ-PR25 analysis was reported. After an initial 25-fold decrease in blood testosterone level, all patients recovered to normal level 12 months after starting ADT. <h3>Conclusion</h3> Despite the lack of differences in terms of EFS between the two arms, this study demonstrated that iSRT+ADT improved MFS without impaired quality-of-life for patients with persistently elevated PSA after RP.