Serum prostate-specific antigen after radiation therapy for clinically localized prostate cancer: Prognostic implications

Abstract

Purpose : Serum prostate-specific antigen (PSA) levels following definitive radiation for prostate cancer are increasingly recognized as the most sensitive means to monitor disease status. However, beyond general agreement that patients fare poorly when posttreatment PSA levels fail to normalize, many questions relative to postirradiation PSA remain unanswered. This study evaluates the potential prognostic value of postirradiation PSA in a large cohort of patients followed with serial PSA determinations. Methods and Materials : We analyzed disease outcome in 427 patients with clinical stages T 1 (122 men), T 2 (147 men), T 3 (152 men), and T 4 (six men) prostate cancer receiving definitive external radiation as sole therapy and followed for times ranging from 9–73 months (median 30 months) with a total of 2260 posttreatment PSA values. Results : Excluding three patients who died due to intercurrent illness without a posttreatment PSA, postirradiation PSA fell in 416 of 424 men (98%). Prostate-specific antigen levels continued to fall for up to 12 months but there was no evidence of significant declines beyond that. The time to nadir PSA was: 3 months, 60 patients; 6 months, 68 patients, 9 months 148 patients; 12 months, 144 patients. Time to nadir was not a significant determinant of outcome. Prostate-specific antigen levels at 3 and 6 months and the nadir level were individually highly correlated with outcome. In multivariate analyses of posttreatment values, only the nadir value was independently significant, with increasing relapse rates as its value was higher. It retained significance when pretreatment PSA level was included in the model. Nadir values ranged from undetectable (52 patients) to 20.3 ng/ml with a median of 1.1 ng/ml. Nadir values down to 1 ng/ml were prognostic; below 1 ng/ml (182 patients) the nadir value no longer yielded prognostic information additional to that inherent in the pretreatment value. Only patients with nadir levels < 1 ng/ml fared well (5-year incidence of relapse or rising PSA 17%); however, if the pretreatment level exceeded 30 ng/ml, then even a nadir level < 1 ng/ml was associated with a 40% failure rate at 5 years. Conclusion : The nadir PSA value after radiation is a significant posttreatment determinant of outcome and was second only to the pretreatment value. Surprisingly low nadir values were prognostically significant. Only patients whose nadir falls below 1 ng/ml can be said to have achieved a biochemical complete remission. However, even such low nadir values do not portend durable disease control for patients with high pretreatment PSA levels.