To report biochemical relapse-free survival (bRFS) after radiotherapy (RT) for localized prostate cancer with two separate failure definitions and compare the results with those after radical prostatectomy (RP).

The study sample comprised 2516 patients with a median follow-up of 78 months. Biochemical relapse after RT was defined as either the American Society for Therapeutic Radiology Oncology definition (definition A [DefA]) or a prostate-specific antigen elevation of more than 2 ng/mL greater than the nadir prostate-specific antigen level (definition N [DefN]). Failure after RP was defined as a prostate-specific antigen level greater than 0.2 ng/mL.

Compared with DefA, DefN resulted in a 13% greater bRFS rate at 5 years and a 12% lower bRFS rate at 10 years. On multivariate analysis, the treatment modality (RP versus RT) was a significant predictor of bRFS using DefA in favor of RP (P <0.001), but was not with DefN (P = 0.87). Higher radiation doses were independently associated with a better outcome with either definition.

Compared with DefA, DefN resulted in better outcomes for up to 7 years after RT, but worse outcomes thereafter. The use of DefA versus DefN resulted in opposite conclusions about the relative efficacies of RT and RP, with DefN suggesting RT is equivalent to RP and DefA that it is worse than RP. Different definitions of biochemical failure after RT can result in differences in the conclusions about treatment efficacy in men with localized prostate cancer, thereby potentially affecting clinical decisions.