Advantages of prostate-specific antigen (PSA) clearance model over simple PSA half-life computation to describe PSA decrease after prostate adenomectomy

ObjectivesA population kinetic approach based on PSA clearance (CL_PSA) may be a more rational strategy to characterize prostate-specific antigen (PSA) decrease profile after prostate surgery than the commonly used method (half-life from mono/bi-exponential models).MethodsWe used 182 post-adenomectomy PSA concentrations from 56 benign prostatic hyperplasia patients to build, with NONMEM software, a multi-exponential and a CL_PSA model for comparison.ResultsThe best multi-exponential model was PSA(t) = 4.96e^? 0.269t + 3.10e^? 0.16t + 0.746e^+ 0.0002t with a stable median residual PSA at 0.64 ng/mL. The best model parametrized with clearance was CL_PSA = 0.0229 ^? (AGE/69)^3.78. Akaike information criteria and standard errors favored the CL_PSA model. Median peripheral zone and transitional zone productions were 0.034 ng/mL/cm³ and 0.136 ng/mL/g. A threshold at 2 ng/mL on day 90 allowed for a diagnostic of biochemical relapse diagnostic.ConclusionsThe population CL_PSA model was superior to the multi-exponential approach for investigating individual post-adenomectomy PSA decreases.