Impact of PSMA PET/CT Staging on Long-Term Outcomes in Patients with Clinically Localized Prostate Cancer: Results of a Large Single-Center Cohort

Prostate-specific membrane antigen (PSMA) PET/CT has become the gold standard for staging and restaging prostate cancer, with superior diagnostic accuracy over conventional imaging and established prognostic value. However, there are limited data on whether PSMA PET/CT–improved staging accuracy is associated with improved long-term patient outcomes. This study analyzes the association between PSMA PET/CT at primary staging and overall survival (OS), biochemical recurrence (BCR), and cancer-specific survival (CSS) in a large university hospital cohort at a center where PSMA PET/CT has been clinically available for over 13 y. Methods: This retrospective single-center study included all 11,146 patients with prostate cancer diagnosed between 2013 and 2023. The final analysis cohort consisted of 6999 patients, of whom 505 (7.2%) underwent PSMA PET/CT for primary staging. We classified patients into 3 groups using D’Amico risk classification. Survival analyses were performed using Kaplan–Meier methods and adjusted Cox regression models. To control for selection bias, propensity score matching and overlap weighting were applied. Landmark analysis addressed selection and immortal time biases, and Fine–Gray models accounted for competing risk of death in a BCR analysis. Results: PSMA PET/CT was associated with a longer time to BCR (hazard ratio [HR] = 0.51; 95% CI, 0.38–0.68; P < 0.001), longer CSS (HR = 0.37; 95% CI, 0.22–0.61; P < 0.001), and longer OS (HR = 0.54; 95% CI, 0.40–0.70; P < 0.001). PSMA PET imaging was associated with particularly better outcomes in high-risk patients, especially those treated with radiotherapy. In the radiotherapy group, the HRs were 0.42 for OS, 0.42 for BCR, and 0.25 for CSS (all P < 0.001), whereas no statistically significant association was observed in patients undergoing radical prostatectomy. As the formal interaction test between PSMA PET/CT and treatment modality was not statistically significant, this differential finding should be considered exploratory. Across all 9 sensitivity analyses, HRs were consistently below 1, indicating a uniform direction of benefit. Conclusion: The association observed in this large real-world cohort supports the clinical value of PSMA PET/CT for primary staging. Findings were particularly favorable among high-risk patients undergoing radiotherapy, although this subgroup difference should be interpreted as exploratory given the nonsignificant interaction test. These results support a potential role for PSMA PET/CT in improving patient selection and detecting oligometastatic disease, enabling higher precision in treatment planning.