Phase III results of adjuvant radiotherapy (RT) versus wait-and-see (WS) in patients with pT3 prostate cancer following radical prostatectomy (RP)(ARO 96-02/AUO AP 09/95): Ten years follow-up.

Abstract

4 Background: Adjuvant RT for pT3 R1 or R0 patients (pts.) after RP remains controversial. The EORTC-phase-III- study suggested a 20% better biochemical control (bNED) after 10 years for RT but no survival advantage. In contrast, the SWOG trial stated not only a gain in bNED but also an improved metastasis free and overall survival after 12 years follow-up. Now, 10-years results from the ARO 96-02 study are available, which are based on the most precisely defined cohort among the three trials. Methods: 385 men with prostate cancer were randomized to either 60 Gy RT (arm A; n=193) or WS (arm B; n=192) before achieving an undetectable PSA. Pts. were stratified for Gleason-score, margin status, neoadjuvant hormonal treatment and stage (pT3a+b vs. c). When the undetectable PSA-level after RP was not achieved, progressive disease was stated and the pts. left arm A/B. Data analysis was by intent-to-treat (ITT). PSA-progression for pts. with undetectable post-RP PSA was defined as two consecutive increasing PSA. The primary endpoint was bNED. The study was powered to demonstrate a 15% increase in bNED for RT. Results: 78 pts. (20%) did not achieve an undetectable PSA and were stated as progressive disease (arm A: 45 pts., arm B: 33 pts.). Additionally, 34 pts. (23%) from the RT-arm did not receive RT. Therefore, 114 pts. had RT (arm A) and 159 pts. WS (arm B). Median follow up was 111.3 months for arm A and 113.3 months for arm B . bNED at 10 years increased to 56% for arm A (RT) compared with 35% for arm B (WS) (hazard ratio= 0.51; p = 0.00002. Out of 307 ITT pts., 15 died from prostate cancer, 23 for other and 5 for unknown reasons. There was no significant profit from ART regarding the endpoints metastasis-free survival (p=0.56) or overall survival (p=0.59). Worst late side effects to the rectum were two grade 2 cases after ART. Grade ≥2 bladder toxicity occurred in 4 out of 148 ITT pts. No grade 4 events were reported. Conclusions: With only one grade 3 case of late toxicity, ART was safe in pT3 prostate cancer. At 10 years median follow up, it reduced the risk of bNED by 49%. The study was not powered to detect differences in OS. Clinical trial information: ARO 96-02/AUO AP 09/95.