PURPOSE: To assess the impact of pretreatment prognostic factors plus subsequent biochemical failure on overall survival after radiotherapy for prostate cancer. METHODS AND MATERIALS: We analyzed the prostate-specific antigen (PSA) and survival records of 1571 men with clinically localized prostate cancer treated with external beam radiotherapy monotherapy at the former Queensland Radium Institute between 1990 and 1997. The pretreatment PSA level, biopsy Gleason score, clinical stage, patient age, and the development of biochemical failure were assessed in relationship to overall survival and cause-specific survival, using fixed, as well as time-dependent, statistics. RESULTS: The median follow-up was 88.1 months (95 months for those still alive). The actuarial overall survival, cause-specific survival, and biochemical failure-free survival rate at 10 years was 61.1%, 80.9%, and 25.9% respectively. Cause-specific survival was independently influenced by the pretreatment PSA level, Gleason score, clinical stage, and the development of biochemical failure (relative risk, 19.1). Using the overall survival endpoint, multivariate analysis showed age, pretreatment PSA level, Gleason score, and biochemical failure (relative risk 1.27) to be statistically significant variables. CONCLUSION: In addition to previously identified factors, the pretreatment PSA level and occurrence of biochemical failure after radiotherapy for prostate cancer are associated with an increased overall mortality risk. Both pretreatment PSA level and posttreatment biochemical failure are independent predictors of overall survival after radiotherapy for prostate cancer.