Incidence and oncologic outcomes of patients with prostate‐specific antigen persistence after radical prostatectomy

BACKGROUND: Patients with postradical prostatectomy (RP) prostate-specific antigen (PSA) persistence (PPP) have been grouped with patients experiencing biochemical recurrence (BCR) in guidelines and clinical trials, potentially masking their distinct, unfavorable outcomes. The objective of this study was to determine whether patients with PPP constitute a unique, high-risk population. METHODS: The authors conducted a retrospective study of patients with prostate cancer undergoing RP (between January l, 2013 and June 30, 2024) using the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry. Post-RP status was defined as no evidence of disease (NED; never developed detectable PSA), PPP (first PSA remained detectable), and BCR (initially undetectable PSA with PSA ≥0.2 ng/mL later). The following differences were quantified: (1) pre-RP characteristics, (2) pathologic characteristics at RP, (3) subsequent treatment patterns, and (4) differences in mortality outcomes based on postoperative PSA status. RESULTS: Of 15,390 patients with who had a follow-up of 4.0 years (interquartile range, 2.4-4.6 years), 11,019 still had NED, 1919 had PPP, and 2452 developed BCR. Patients who had PPP demonstrated a higher risk pre-RP and post-RP characteristics compared with those who had NED or BCR on unadjusted and adjusted comparisons, with differences that were both statistically significant and clinically meaningful. Patients who had PP had significantly higher PSA values before secondary treatment compared with those who had BCR (median PSA, 0.73 vs. 0.28 ng/mL, respectively; p < .001). The 5-year all-cause mortality rate was 2.5% (95% confidence interval, 2.1%-2.9%) for patients with initially undetectable PSA (NED and BCR combined) and 5.7% (95% confidence interval, 4.3%-5.7%) for patients with PPP (p < .001). CONCLUSIONS: One in eight patients who undergo prostatectomy experience PPP. These patients constitute a unique, high-risk population distinct from patients who have NED and BCR. Clinical trials addressing optimal treatment and intensity for these at-risk patients are critically warranted.