PSMA PET-guided management in high-risk biochemical recurrence after radical prostatectomy: Pros and cons from the experience of a tertiary referral center

Background High-risk biochemical recurrence (BCR) after radical prostatectomy identifies patients at increased risk of metastatic progression and prostate cancer-specific mortality. Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) is increasingly used to localize recurrence and guide treatment; however, its implications for oncologic endpoints and their interpretation in routine practice remain uncertain. Methods We retrospectively analyzed consecutive patients with high-risk BCR after radical prostatectomy who were discussed within a multidisciplinary tumor board at a tertiary referral center. All patients underwent PSMA PET/CT at recurrence, and imaging findings informed subsequent treatment allocation. Outcomes of interest were second BCR-free survival and progression-free survival (PFS). Survival outcomes were evaluated using Kaplan–Meier estimates, restricted mean survival time (RMST), and multivariable Cox proportional hazards regression. For external contextualization, Kaplan–Meier curves from pivotal randomized trials in this setting were reconstructed and used as benchmark references. Results Overall, 136 patients were included. At PSMA PET/CT, 35% had negative findings or isolated local recurrence, 18% had nodal-only disease (miN1M0), and 47% had metastatic disease (miNanyM1). Both second BCR-free survival and PFS differed significantly across PSMA PET categories. Compared with patients with PET-negative/local recurrence, those with miNanyM1 disease had significantly shorter RMST for second BCR-free survival −11.6 months; p < 0.01 and PFS −7.8 months; p < 0.01, whereas miN1M0 disease showed an intermediate-risk profile. In multivariable models, PSMA PET category was the strongest independent predictor of progression. Compared with reconstructed randomized-trial benchmarks, this real-world cohort showed earlier biochemical and radiographic progression. Among patients experiencing second BCR, median time to PET-detected progression was 4.3 months. Conclusion PSMA PET/CT provides clinically meaningful prognostic stratification in high-risk BCR after radical prostatectomy and supports individualized management. However, PSMA PET-guided surveillance may anticipate progression detection, leading to apparent shortening of intermediate endpoints through lead-time bias and stage migration.