Stewart AJ et al. (2005) Prostate-specific antigen nadir and cancer-specific mortality following hormonal therapy for prostate-specific antigen failure. J Clin Oncol 23: 6556–6560

Around 30% of patients with localized prostate cancer who undergo radical prostatectomy or external-beam radiation therapy show PSA failure within 10 years and median survival in these patients is related to PSA doubling time. PSA doubling time prior to the initiation of primary androgen-suppression therapy (AST) has also been associated with prostate-cancer-specific mortality (PCSM), as has posthormonal PSA nadir. Although it has been shown that patients who do not achieve a post-AST nadir below 0.2 ng/ml following primary treatment have an increased risk of PCSM, it is not known whether this also applies in cases of secondary AST given for PSA failure after surgery or radiation therapy.

In this study of 747 men with rising PSA and negative bone scans after radical prostatectomy (n = 486) or external-beam radiation therapy (n = 261), PSA nadir at 8 months post-AST initiation, pre-AST PSA doubling time, PSA level and a Gleason score of 8–10 were significantly associated with time to PCSM. A PSA nadir of >0.2 mg/ml combined with pre-AST PSA doubling time of <3 months was closely associated with PCSM, independent of initial prostate cancer treatment, and this profile was seen in 75% of those patients who died of prostate cancer over the observation period of the study. Given the clinical relevance of these findings, the authors suggest that these criteria are a useful endpoint for future clinical trials.