Androgen deprivation for minimal metastatic disease: Threshold for achieving undetectable prostate-specific antigen

Objectives. To develop objective measures to select systemic therapies for study in large-scale trials for patients with lesser tumor burdens, we explored prostate-specific antigen (PSA) changes after androgen ablation in patients with disease progression after treatment of localized disease. Long-term follow-up of trials incorporating androgen-deprivation with local therapy have shown improved survival relative to local therapy alone. This suggests that the benchmark for treatment of minimal metastatic disease can be cure. Methods. Patients with a rising PSA level with or without clinical metastases after local therapy who received androgen deprivation at Memorial Sloan-Kettering Cancer were identified from two institutional databases. The primary outcome was the proportion achieving an undetectable PSA level, and the pretreatment parameters associated with this endpoint were evaluated. Results. A total of 130 patients who received androgen ablation and were followed up at Memorial Sloan-Kettering Cancer Center were identified. Overall, 31 (57%) of 54 (95% confidence interval 44% to 71%) patients with a rising PSA level alone and 28 (37%) of 76 (95% confidence interval 26% to 47%) patients with a rising PSA level and clinical metastases achieved an undetectable PSA level after androgen ablation (P = 0.02). The PSA level at the start of androgen ablation and the presence of metastases were the most significant predictive factors. Conclusions. The probability of achieving an undetectable PSA level varied inversely with the disease extent. Although achieving an undetectable PSA level does not mean that a patient has been cured, it does establish an endpoint that can be used to identify approaches worthy of study in the Phase III setting.(c) 2005 Elsevier Inc.