Defining biochemical cure for prostate carcinoma patients treated with external beam radiation therapy

Background: The authors retrospectively reviewed their institution's long term experience with conventional external beam radiation therapy (RT) for localized prostate carcinoma to identify criteria associated with long term biochemical cure.

Methods: Between January 1987 and December 1994, 871 patients were treated with external beam RT alone for clinically localized prostate carcinoma at William Beaumont Hospital, Royal Oak, Michigan. All patients received only external beam RT to a median total dose of 66.6 grays (Gy) (range, 59.4-70.4 Gy). No patient received hormonal therapy unless treatment failure was documented. The median follow-up was 5.0 years (range, 0. 2-11.8 years). Biochemical failure was defined according to the American Society for Therapeutic Radiology and Oncology Consensus Panel definition.

Results: In the entire study group, 380 patients experienced biochemical failure at a median interval of 1.5 years after the completion of RT. The 5-year and 7-year actuarial rates of biochemical control were 50% and 48%, respectively. On multivariate analysis, a higher pretreatment prostate specific antigen (PSA) level, higher Gleason score, higher clinical T classification, higher nadir level, and shorter time interval to nadir all were associated significantly with biochemical failure (P < 0.001). The median intervals to biochemical failure for patients with pretreatment PSA levels </= 3.9 ng/mL, 4.0-19.9 ng/mL, and >/= 20.0 ng/mL were 2.2 years, 1.5 years, and 1.2 years, respectively (P < 0. 001). The median intervals to biochemical failure for patients with Gleason scores of 2-4, 5-7, and 8-10 were 1.8 years, 1.5 years, and 1.1 years, respectively (P < 0.001). Only 6 patients failed beyond 5 years after treatment even though 136 patients were at risk for failure beyond this point. When restricting analysis to 643 patients (74%) with >/= 3 years of PSA follow-up, the median nadir level for biochemically controlled patients was 0.6 ng/mL and occurred at a median interval of 1.9 years after RT versus a median nadir level of 1.3 ng/mL (P = 0.002) occurring at a median interval of 1.0 years (P < 0.001) in those patients who experienced biochemical failure. Patients were divided into subgroups based on their PSA nadir level and time to nadir. The 5-year actuarial biochemical control rates for patients with nadir values of </= 0.4 ng/mL, 0.5-0.9 ng/mL, 1. 0-1.9 ng/mL, 2.0-3.9 ng/mL, and >/= 4.0 ng/mL were 78%, 60%, 50%, 20%, and 9%, respectively (P < 0.001). The 5-year actuarial biochemical control rates for patients who reached their nadir at < 1.0 years, 1.0-1.9 years, 2.0-2.9 years, and >/= 3.0 years were 30%, 52%, 64%, and 92%, respectively (P < 0.001). All 52 patients who achieved a nadir of </= 0.4 ng/mL and required >/= 2.0 years to reach this nadir had biochemically controlled disease.

Conclusions: These results suggest that a patient has a high likelihood of biochemical cure after treatment for prostate carcinoma with conventional doses of external beam RT if he has not demonstrated biochemical failure within 5 years of treatment. Patients with lower pretreatment PSA levels and lower Gleason scores may require longer follow-up than those with less favorable characteristics to achieve the same certainty of cure. Patients who achieve a PSA nadir </= 0.4 ng/mL and require >/= 2.0 years to reach this nadir have the highest probability of cure.