Prognostic value of PSMA PET/CT-Based local staging in predicting biochemical recurrence after radical prostatectomy

Purpose: PSMA PET/CT outperforms conventional imaging for detecting pelvic nodal and distant metastasis, but its role regarding local staging and risk stratification remains unclear. This study aims to evaluate the association between PSMA PET/CT characteristics and biochemical recurrence-free survival (BRFS) after robot-assisted radical prostatectomy (RARP) in patients with prostate cancer. Methods: In this international multicentre retrospective study, we analyzed 476 patients with localized or locally advanced miN0 prostate cancer, staged with PSMA PET/CT and MRI before RARP (2016–2023). Predictors of BRFS were identified using univariate and multivariate Cox regression with backward elimination based on Akaike information criterion (AIC). Kaplan-Meier analysis assessed the association of clinical stage by MRI, PSMA PET, and their combination with BRFS. Results: In total 476 patients were included with a median follow-up of 18.0 months (IQR 6.9–29.3). Of the 127 BCRs, 101 (79.5%) occurred within two years post-surgery. The final multivariate model included initial PSA (10–20 vs. <10: HR 1.92 [95% CI 1.21–3.05]; >20 vs. <10: HR 2.26 [95% CI 1.30–3.93]), biopsy ISUP grade group (2–3 vs. 1: HR 2.28 [95% CI 0.70–7.41]; 4–5 vs. 1: HR 3.62 [95% CI 1.12–11.65]), MRI T-stage (T3a vs. ≤T2: HR 1.19 [95% CI 0.75–1.90]; ≥T3b vs. ≤T2: HR 2.09 [95% CI 1.21–3.62]), and PSMA PET T-stage (T3a vs. ≤T2: HR 1.05 [95% CI 0.59–1.85]; ≥T3b vs. ≤T2: HR 2.75 [95% CI 1.63–4.63]). From the full model, clinical T-stage, MRI-derived index diameter, SUVmax, PSMAtotal and PSMAvol were eliminated. The 2-year BRFS was 19% (95% CI 6.7–51%) in patients with T3b disease on both MRI and PSMA PET compared to 58% (95% CI 40–84%) in those with T3b detected only on MRI (p = 0.03). Conclusion: Clinical tumor stage assessed by PSMA PET was independently associated with BRFS in multivariate analysis, adjusting for clinical parameters and MRI-derived staging. This suggests that incorporating PSMA PET-based local staging may improve risk stratification and guide treatment decisions.