68Ga-PSMA-11 in Staging of Unfavorable Intermediate- and High-Risk Prostate Cancer Reduces Indication for Noncurative Prostatectomy: A Prospective, Multicenter, IAEA Study.

Accurate staging of unfavorable intermediate- or high-risk prostate cancer (PCa) is essential for treatment decisions. Conventional imaging often fails to detect lymph node, bone, and visceral metastases, and for this purpose 68Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT is clinically used. This prospective, multicenter, International Atomic Energy Agency-supported trial evaluated the accuracy of 68Ga-PSMA-11 PET/CT for initial staging compared with MRI and histopathology and the impact of 68Ga-PSMA-11 PET/CT on determining surgical eligibility. Methods: In a prospective, international study supported by the International Atomic Energy Agency, 775 patients with high-risk or unfavorable intermediate-risk PCa from 12 centers across 11 countries-including low-, middle-, and high-income settings, scheduled for radical prostatectomy based on conventional imaging (including bone scanning and pelvic MRI) underwent 68Ga-PSMA-11 PET/CT before treatment. PET and MRI findings were compared with radical prostatectomy histopathology, and the impact of PET on radical prostatectomy was assessed. Results: 68Ga-PSMA-11 PET/CT detected metastatic disease (M1) in 20.4% of cases, altering management and preventing prostatectomy in 24.0%. The accuracy for seminal vesicle invasion was 90.1% for 68Ga-PSMA-11 PET/CT versus 57.3% for MRI, and for lymph node metastases it was 91.1% for 68Ga-PSMA-11 PET/CT versus 69.7% for MRI. In 13.1% of patients (78/593), there were discordant results between 68Ga-PSMA-11 PET/CT and histopathology. 68Ga-PSMA-11 PET/CT had false-negative lymph node findings in 8.6% of cases, with the most clinically significant being 4.5% of patients incorrectly staged as N0. False-positive lymph node findings at 68Ga-PSMA-11 PET/CT occurred in 4.5% of patients. Conclusion: 68Ga-PSMA-11 PET/CT significantly improves staging accuracy, reducing the indication for prostatectomy and impacting treatment decisions. These findings, from a broad international cohort including low-, middle-, and high-income countries, support the global adoption of 68Ga-PSMA-11 PET/CT into standard staging protocols for high-risk PCa.