32 Background: In the ARO 96-02 trial, patients with pT3 prostate cancer were randomly assigned before achieving an undetectable prostate-specific antigen (PSA) after radical prostatectomy (RP) to receive a wait and see policy (arm A) or adjuvant radiotherapy (RT) (arm B). If the undetectable PSA level was not achieved, patients were excluded by protocol and received RT with 66 Gy (arm C). Methods: Three hundred eighty eight patients with pT3-4 pN0 prostate cancer with positive or negative surgical margins were recruited; 78 retained a detectable PSA (median 0.6 ng/mL, range 0.05-5.6 ng/mL) after RP; 74 of them were irradiated with 66 Gy to the prostatic fossa. Radiotherapy was applied in median 86 days post-RP. Results: Compared to patients in arm A and B, the patients with persisting PSA after RP had higher preoperative PSA values (p<0.0001), higher tumor stages (p=0.0057), higher grades (more G3 tumors), higher Gleason scores (p=0.0013) and more positive surgical margins (p=0.033). For the 74 patients, the 10 years clinical relapse-free survival rate was 63%. Forty three men had hormonal therapy, 12 developed distant metastases; 23 patients died. Compared to patients who did achieve an undetectable PSA (arms A+B), arm-C patients fared significantly worse with a 10 year overall survival of 68% versus 84% (p=0.0019). The rate of developing distant metastases within 10 year post-RP was 2.5 fold higher (14.6 vs. 5.8%) for men with a persisting PSA compared with the patients in arm A (p=0.0079). Metastasis-free survival after 10 years was 67% in arm C versus 81% in arm B (p=0.01). Conclusions: A persisting PSA after prostatectomy seems to be an important prognosticator of clinical progression for pT3 tumors which should then prompt aggressive treatment. It correlates with a higher rate of distant metastases and with worse overall survival. The results underline the significance of achieving an undetectable PSA after radical prostatectomy.