Introduction

A short PSA doubling time (PSADT), calculated using PSA values ≥0.2 ng/ml, after biochemical recurrence (BCR) post radical prostatectomy (RP) portends a poor prognosis. We tested if ePSADT, calculated from the first detectable PSA after RP and including all values up to and including the first BCR value, predicts castration-resistant PC (CRPC), metastases, all-cause mortality (ACM) and PC-specific mortality (PCSM).

Methods

Cox proportional hazards were used to test the association between ePSADT and CRPC, metastases, ACM, and PCSM in 674 men in the SEARCH database who underwent RP between 1988-2015 and later recurred. Men had to have at least 2 PSA values separated by at least 3 months to calculate ePSADT. Men who started salvage therapy within this time were censored and did not have ePSADT calculated. Thus, all PSA values used were prior to subsequent therapy. ePSADT was examined as a log-transformed continuous and categorical variable.

Results

During a median 69-month follow-up (IQR 35-117) after BCR, 43 developed CRPC, 59 metastases, 236 all-cause deaths, and 30 PC-specific deaths. After adjusting for multiple clinicopathological variables, log-transformed ePSADT was not associated with any outcome. However, when ePSADT was categorized as ≥15, 9-14.9, 3-8.9, and <3 months, those with ePSADT <3 months were at increased risk of CRPC (HR 6.20, p=0.004), metastases (HR 5.26, p=0.002), PCSM (HR 5.06, p=0.017), and ACM (HR 1.63, p=0.070) vs. ePSADT ≥15 months, though the association with ACM was not significant. Similarly, ePSADT 3-9 months increased risk of CRPC (HR 3.56, p=0.015), metastases (HR 1.92, p=0.13), PCSM (HR 3.17, p=0.044), and ACM (HR 1.67, p=0.006) vs. ePSADT ≥15 months, though the association with metastases was not significant. See figure for CRPC risk by ePSADT.

Conclusions

Shorter ePSADT, particularly ePSADT <9 months, calculated using PSA values before and up to BCR, is associated with increased risk of CRPC, metastases, PCSM, and ACM among men with BCR after RP. ePSADT allows for risk-stratification at the time of BCR and before PSADT is calculable allowing these men to receive early aggressive secondary treatment and/or be enrolled on clinical trials.

Funding

none