Can PSA Kinetics Improve the Yield of PSMA PET/CT in Biochemical Recurrence after Prostatectomy?

Introduction & Objectives Biochemical recurrence (BCR) after radical prostatectomy (RP) occurs in approximately 20–40%. PSMA PET/CT is the preferred imaging modality for detecting recurrence; however, detection rates decline sharply when PSA is < 1 ng/mL, leading to more negative scans, added costs and radiation exposure. PSA kinetics, which reflect tumour aggressiveness, have been correlated with PET positivity in mixed cohorts, but their role in post-prostatectomy BCR exclusively remains unclear. Our study aimed to evaluate the association between PSA kinetics and PSMA PET/CT positivity in post-RP BCR and to define clinically relevant kinetic cut-offs to improve imaging yield. Materials & Methods A retrospective analysis of post-RP patients (2013–2024) who developed BCR and underwent 68Ga-PSMA PET/CT was performed. Patients with prior therapy, PSA persistence, inadequate follow-up, or non-PSMA imaging were excluded. Institutional Ethics Committee approval was obtained prior to data collection. Baseline, pathological, and PSA kinetic parameters were compared between PET-positive and PET-negative cohorts. Logistic regression was used to assess correlation between PSA kinetics and PET positivity, and ROC analysis identified optimal cut-offs. Results A total of 973 men underwent RP during the study period. After applying the inclusion and exclusion criteria, 64 patients were included in final analysis. The median age was 67 years. 19 patients (29.7%) had positive scans, while 45 (70.3%) had negative scans. Baseline and pathological characteristics were comparable between the two groups. Median PSA at the time of imaging was 0.58 ng/mL. PSA kinetics differed significantly between groups. PET-positive patients had higher PSA velocity (1.50 ± 2.20 vs 0.39 ± 0.42 ng/mL/year, p = 0.02) and shorter doubling time (4.40 ± 4.03 vs 8.68 ± 7.91 months, p = 0.009). On univariate analysis, PSA velocity (PSAV) (OR 3.31, 95% CI 1.14–9.58, p = 0.027), PSA doubling time (PSADT) (OR 0.86, 95% CI 0.75–1.00, p = 0.050), and PSA at imaging (OR 10.68, 95% CI 1.23–93.11, p = 0.032) were significant predictors of PET positivity. On ROC analysis, PSA-DT and PSAV showed good discriminatory power (AUC 0.71 and 0.69, respectively) with optimal cut-offs of 3.8 months and 0.5 ng/mL/year respectively. Conclusion Patients with PSA-DT < 4 months or PSAV > 0.5 ng/mL/year are more likely to have positive scans. Integration of PSA kinetics into imaging decisions can improve the yield. However, prospective studies with large sample size are needed for validation.