The purpose of this study was to present patterns and risk of biochemical failure following external beam irradiation of prostate cancer and to make comparisons to a published modern radical prostatectomy series. Between January 1987 and December 1994, 328 men were treated definitively at Fox Chase Cancer Center for localized prostate cancer using conventional or three-dimensional conformal radiotherapy. The median biochemical follow-up was 6.4 years, with all patients having at least 5 years follow-up. Two prognostic patient groups were established on the basis of proportional hazards modeling that considered treatment and presenting tumor characteristics. For each of the two prognostic groups, biochemical failure and hazard functions were estimated using the ASTRO consensus definition of failure and life table methodology. Failure risk comparisons were made to modern published radical prostatectomy series. Multivariate analysis demonstrated the independent predictive power of pretreatment PSA level, palpation stage, Gleason score, and dose. Thus, the favorable prognosis group, Group I, consisted of 83 patients who were treated with a dose level > or = 74 Gy and who presented with PSA levels < 20 ng/ml, T1/T2A tumors, and Gleason score 2-6. Group II consisted of 245 patients with at least one of the following: pretreatment PSA level > or = 20 ng/ml, T2B/T3 tumor, Gleason score 7-10, dose < 74 Gy. The 5- and 8-year bNED estimates were 76% and 76% for Group I, and 51% and 49% for Group II. Only three failures occurred after 5 years, all from Group II, representing 2% of the total failures observed. Hazard function estimates indicate maximum risk of failure at 24 to 36 months, tapering to a low rate at 4 years with no failures observed after 6 years. Differences in patterns of failure by prognostic group show maximum risk of failure at 24 months (median, 31 months) for Group I, and 12 to 36 months (median, 22 months) for Group II. Group II reaches low levels of risk at 6 years, in contrast to 4 years for the patients with a more favorable prognosis. We concluded that patients treated with external beam radiation alone show little risk of failure after 4 to 6 years. This result suggests that the 5-year bNED control rate approximates the eventual cure rate of prostate cancer.