The fall and rise of prostate-specific antigen: Kinetics of serum prostate-specific antigen levels after radiation therapy for prostate cancer

BACKGROUND: The serum kinetics of prostate-specific antigen (PSA) after radiation therapy for prostate cancer are not well characterized, and the potential prognostic significance of serum half-lives and of serum doubling times is unclear. This study was designed to address those issues. METHODS: One hundred fifty-four patients with at least four serial PSA determinations who received external-beam radiation therapy alone were analyzed to determine PSA kinetics and to correlate kinetic parameters with outcome. Nonlinear regression techniques were used to estimate PSA half-lives and doubling times. RESULTS: The PSA data fitted well to exponential models consistent with the hypothesis that PSA kinetics after radiation follow first-order (exponential) kinetics. The mean PSA half-life was 1.9 months (range, 0.5 to 9.2 months). No significant correlation existed between half-life and grade, stage, acid phosphatase level, serum testosterone level, or patient age. A weak correlation between half-life and pretreatment PSA level was observed: patients with low PSA levels tended to have longer half-lives. Half-life did not correlate with disease relapse or with the likelihood of developing a rising PSA profile. PSA doubling time in 37 patients with rising values ranged from 1.6 to 53 months (mean, 12.5 months). Doubling times were significantly longer than half-lives by an average factor of 6.5 and there was no correlation between half-life and subsequent doubling time. Doubling times were longer in low-grade tumors. CONCLUSIONS: Serum kinetics of PSA in particular its rate of fall after radiation provide little, if any, useful clinical information. It is possible that serum kinetics of PSA are related to tumor cell kinetics but such relationships remain speculative. Correlative cell kinetic--PSA kinetic studies are needed to elucidate the mechanisms underlying the changes in PSA level after radiation therapy.