BACKGROUND: To improve the early detection of responders to salvage external beam radiotherapy (RT) after radical prostatectomy (RP). METHODS: Between 2002 and 2007, in a single institution, 136 consecutive patients received salvage RT to a dose of 66 Gy without androgen-deprivation therapy after RP for a rising prostate-specific antigen (PSA) level. PSA measurements were systematically performed before RT (PSART), at the fifth week of RT (PSA5), and in the follow-up at least twice a year (every 6 mo). The PSA level decline during RT was expressed as PSA ratio (PSA5/PSART). Two different definitions of biochemical failure after salvage RT were considered: PSA level\textgreater0.4 ng/ml and PSA\textgreaterPSA nadir post-RT +0.4 ng/ml. Statistical analyses included univariate and multivariate Cox regression models. RESULTS: The median follow-up was 60 months. The 5-year freedom from biochemical and clinical failure rates were 57% (95% CI: 48%-66%) and 92% (95% CI: 87%-97%), respectively. The mean PSA5 was 0.61 ng/ml (range: 0-7) and the mean PSA ratio was 0.67 (0-1.7). A PSA ratio\textless1 was a significant prognostic factor in multivariate analysis for both definitions of biochemical failure (P = 0.01 for both) and for clinical failure (P = 0.005). CONCLUSIONS: For patients undergoing salvage RT after RP for a rising PSA level, the absence of PSA level decline during RT is predictive of biochemical and clinical failure and may be used to rapidly identify poor responders