Time from first detectable PSA following radical prostatectomy to biochemical recurrence: A competing risk analysis

Abstract

Introduction: In this study, we estimated the time from first detectable prostate-specific antigen (PSA) following radical prostatecfollowing radical prostatectomy (RP) to commonly used definitions of biochemical recurrence (BCR). We also identified the predictors of time to BCR. Methods: We identified subjects who underwent a RP and had an undetectable PSA after surgery followed by at least 1 detectable PSA between 2000 and 2011. The primary outcome was time to BCR (PSA ≥0.2 and successive PSA ≥0.2) and prediction of the rate of PSA rise. Outcomes were calculated using a competing risk analysis, with univariable and multivariable Fine and Grey models. We employed a mixed effect model to test clinical predictors that are associated with the rate of PSA rise. Results: The cohort included 376 patients. The median follow-up from surgery was 60.5 months (interquartile range [IQR] 40.8-91.5) and from detectable PSA was 18 months (IQR 11-32). Only 45.74% (n = 172) had PSA values ≥0.2 ng/mL, while 15.16% (n = 57) reached the PSA level of ≥0.4 ng/mL and rising. On multivariable analysis, the values of the first detectable PSA and pathologic Gleason grade 8 or higher were consistently independent predictors of time to BCR. In the mixed effect model rate, the PSA rise was associated with time from surgery to first detectable PSA, Gleason score, and prostate volume. The main limitation of this study is the large proportion of patients that received treatment without reaching BCR. It is plausible that shorter estimated median times would occur at a centre that does not use salvage therapy at such an early state. Conclusion:The time from first detectable PSA to BCR may be lengthy. Our analyses of the predictors of the rate of PSA rise can help determine a personalized approach for patients with a detectable PSA after surgery. IntroductionRadical prostatectomy (RP) is the surgical treatment of choice for clinically localized prostate cancer. Prostatespecific antigen (PSA) monitoring is the primary tool for detecting relapse of cancer after RP. About 27% to 53% of men undergoing RP will have a detectable serum PSA within 10 years of surgery.1-5 Although biochemical recurrence (BCR) is an ominous finding and is associated with an increased risk of progression to metastatic disease, 6 it precedes clinical recurrence by many years.7-9 Furthermore, many patients with BCR will never progress.Currently, level 1 evidence suggests that adjuvant radiation should be administered to patients with high-risk prostate cancer following RP.10-13 However, adjuvant radiation has not been compared to early salvage radiation. [14][15][16] Therefore, most urologists would rather use early salvage therapy, most commonly offered after reaching BCR rather than after the first detectable PSA. 17 To the best of our knowledge, the time frame from the first detectable PSA to BCR has not been explored.In this study we used the 4 most accepted definitions for BCR: (1) PSA ≥0.2 ng/mL; (2) an initial PSA of ≥0.2 ng/mL and successive PSA ≥0.2 ng/mL; ...