To evaluate retrospectively the efficacy of adjuvant radiation therapy (ART) in patients with T1-T2 prostate cancer (CaP) in whom extracapsular cancer (pT3) was detected after radical prostatectomy (RP), together with biochemical failure characterized by a recurrent level of serum prostate-specific antigen (PSA)>0.1 ng/mL. Twenty-two patients with T1-T2 CaP treated by RP who subsequently were found to have pT3 CaP with (13) or without (9) positive surgical margins and/or seminal vesicle invasion, exhibited biochemical failure characterized by a recurrent level of serum PSA, 2-40 (mean: 25) months after RP and were treated with ART (65 Gy). Bone and CT scans were negative in every patient, 15 of whom were submitted to TRUS biopsy (Bx) of the anastomosis (resection site), which was positive in 8. Patients were followed up for between 6 and 60 (mean: 32.5) months. Transient side effects (urgency, proctitis, diarrhea) were experienced by 9 patients after ART. A decrease in serum PSA was observed in 19 patients; however, only 14 of these achieved an undetectable level (<0.1 ng/mL) on one or more occasions after completion of ART (in 12 cases this was after 3 months). Of the 14 patients, 8 achieved a persistently unmeasurable PSA level at a mean follow-up of 20.4 (range: 9-48) months. There was no difference between patients in whom an undetectable level of serum PSA was attained and those in whom it was not, with regard to specimen pathology, PSA doubling time, timing of ART, and the result of Bx. Patients who achieved an undetectable PSA had a lower mean PSA at the time of ART (1.1 vs 2.9 ng/mL, P<0.05) and a lower preoperative mean PSA. Although ART for biochemical failure after RP may lead to undetectable PSA levels in a significant proportion of patients for a significant period of time, a longer follow-up shows that such unmeasurable levels persist in only 36.4% of such patients.