Persistent prostate-specific antigen levels after radical prostatectomy as a prognostic marker and a guide for early treatment in the era of PSMA-based diagnostics

Aim. To assess the frequency, risk factors, and prognostic value of persistent prostate-specific antigen (PSA) levels 3 months after radical prostatectomy (RP), and to evaluate the role of positron emission tomography combined with computed tomography, with prostate-specific membrane antigen (PSMA-PET/CT) and early treatment strategies in patients with PSA persistence.

Materials and methods. A retrospective study of 837 patients with prostate cancer (PCa) who underwent RP between 2019 and 2024. PSA persistence was defined as a level ≥0.1 ng/mL at 3 months postoperatively. Clinicopathological features, biochemical and metastatic outcomes were analyzed. Predictive models using logistic regression and machine learning algorithms (MLP, Random Forest) were developed. ROC curve analysis (AUC) and Kaplan–Meier survival curves were used to assess predictive accuracy and metastasis-free survival.

Results. PSA persistence was observed in 285 patients (34.0 %). It was significantly associated with high-grade disease (ISUP ≥3 (ISUP – International Society of Urological Pathology); hazard ratio 2.10; p = 0.001) and advanced pathological stage pT3–T4 (p = 0.039), but not with positive surgical margins (p = 0.92). Predictive models showed moderate accuracy (AUC 0.59–0.60), with preoperative PSA being the most important feature (>40 % contribution in Random Forest). Three-year metastasis-free survival was 98.5 % in the persistence group vs 99.7 % in the non-persistence group (p >0.3). PSMA PET/CT identified residual disease in 68 % of persistent PSA cases and influenced treatment decisions.

Conclusion. Persistent PSA at 3 months post-RP is a common and clinically relevant marker, strongly associated with aggressive disease. Early detection using PSMA PET/CT and risk-adapted salvage treatment improve disease control and metastasis-free outcomes.