Timing of Prostate-specific Antigen Nadir After Radical Prostatectomy and Risk of Biochemical Recurrence

Abstract

Objectives: To evaluate the association between PSA nadir level and time to nadir (TTN) with biochemical recurrence (BCR) risk after radical prostatectomy (RP) in the SEARCH database. Methods: Retrospective analysis of 1,939 men from the SEARCH database treated with RP between 1998–2015 with available ultrasensitive PSA nadir within 1–6 months after RP. Uni- and multivariable analyses of PSA nadir and TTN with time from nadir to BCR were done with Cox models (adjusted for demographics, tumor features and preoperative PSA). Results: Among men with an undetectable PSA nadir, the TTN was unrelated to BCR (1–2.9 vs. 3–6 months: HR 0.86, p=0.46). Regardless of TTN, men with detectable nadir had increased risk of BCR (TTN 3–6 months: HR 1.81, p=0.024; TTN 1–2.99 months: HR 3.75, p<0.001 vs. undetectable nadir and TTN 3–6 months). Among men with a detectable PSA at 1–3 months, 53% had a lower follow-up PSA 3–6 months after RP which was undetectable in 32% and lower but still detectable in 21%. Conclusions: In the post-RP setting, men with both a detectable nadir and a shorter TTN had an increased risk of BCR. Intriguingly, about half of the men with a detectable PSA in the first 3 months after RP had a lower follow-up PSA between 3 and 6 months after RP. If confirmed in future studies, this has important implications for patients considering adjuvant therapy based upon post-operative PSA values in the first 3 months after RP.

Ultrasensitive prostate‐specific antigen level as a predictor of biochemical progression after robot‐assisted radical prostatectomy: Towards risk adapted follow‐up

“…Based on our results, a USPSA of 0.02 ng/mL is associated with a 2.7 times higher BCR risk compared to a value of 0.01 ng/mL while USPSA values of 0.06 were associated with 12 times higher risk of BCR. Similarly to our observations, Stephanie et al recently showed that patients with USPSA nadir levels of >0.01 ng/mL had increased risk of BCR (OR = 3.75, P < 0.001) . Vesely et al in a single‐institution study of 319 men found that USPSA nadir >0.1 ng/mL and time to nadir <3 months are independent predictors of BCR.…”

<p>Prognostic significance of a novel indicator (PSA_postd3/PSA_pre) for PSA recurrence in patients after radical prostatectomy</p>

“…Postoperative PSA after RP is a frequent factor included in various clinical outcome (including PSA recurrence) prediction tools in PCa patients 23. Previous research usually focused on the relationship between the absolute value of postoperative PSA and PSA recurrence 5–7,23–26. For example, Vesely held that PSA on day 30 postop was significantly associated with PSA recurrence, but such an association was not observed with PSA on day 14 postop 23.…”

Surrogate endpoints in early prostate cancer research

“…The nPSA level has been suggested to have a significant impact on outcome in both the surgical ( 27 , 28 ) and radiation therapy ( 29 , 30 ) groups in multiple studies. Nadir levels are used as continuous covariates in models, or dichotomized as detectable or undetectable based on a variety of levels.…”

“…Time to nPSA is often suggested to be a valid surrogate of outcome ( 33 - 35 ), but is frequently compounded by bias ( 36 ) (discussed later). By conducting a landmark analysis to minimize such bias, Skove et al ( 28 ) found that a time to nadir inside 3 months was associated with subsequent bF less often than an nPSA between 3 and 6 months in a retrospective post-prostatectomy dataset.…”