Estimation and Prognostic Role of Prostate-specific Antigen (PSA) Doubling Time After Radical Prostatectomy

There are several methods for estimating prostate-specific antigen (PSA) doubling time (DT), and many men exhibit long periods of undetectable PSA below 0.1 ng/ml after radical prostatectomy (RP). We quantified between-method differences in estimated PSA-DT at PSA relapse after RP and evaluated how these differences affect discrimination of prostate cancer (PCa) death.

Men who underwent RP in 2007-2024 and subsequently developed a PSA relapse, defined as two consecutive values above 0.2 ng/ml, were included. We estimated PSA-DT from the date of the first undetectable PSA after RP until PSA relapse using four methods: (1) all detectable PSAs only, (2) two most recent detectable PSAs, (3) three most recent PSAs (with the third forced to 0.1 ng/ml if ≤0.1 ng/ml), and (4) all PSAs using a missing data approach. Discrimination of 10-yr PCa death was assessed using concordance index (C-index).

A total of 3826 men were included. Median PSA-DT ranged from 4.4 to 8.6 mo, with a wide range in PSA-DT across different estimation methods. All four methods discriminated PCa death to a similar level, with C-index ranging from 0.70 to 0.74, which was slightly lower than the C-index (0.77) for the absolute PSA level at relapse. This study was restricted to men with PSA relapse after RP and may not be generalizable to other patient categories.

PSA-DT after RP was sensitive to the choice of estimation method, and all methods had comparable prognostic value to the last measured PSA level.