Utility of PSMA PET/CT After an Initial Negative Scan: Results from a Prospective Multicenter PSMA PET Registry

There is a paucity of data on the utility of a second prostate-specific membrane antigen (PSMA) PET/CT scan after an initial negative scan in patients with recurrent prostate cancer. The purpose of this study was to assess the utility of a second PSMA PET/CT scan in these patients. Methods: This cohort comprised patients in the PSMA PET Registry for Recurrent Prostate Cancer in Ontario, Canada, who were recruited in 1 of 6 predefined clinical cohorts between October 2018 and September 2022 who had more than 1 PSMA PET/CT scan and whose initial scan was negative. The scan positivity rate, serum prostate-specific antigen (PSA), PSA doubling time, and management change were compared with baseline data. Results: In total, 210 of the 4140 patients in the registry fulfilled the inclusion criteria for the current analysis. The positivity rate of the second PET scan was lower than the baseline PET scan (56.2% [118/210] vs. 68.4% [2832/4140], P = 0.0002). Detection rates were higher in patients with elevated serum PSA (66.9% [107/160] for PSA of 0.5 ng/mL) and a PSA doubling time of less than 12 mo (64.7% [75/116]). Although differences in disease distribution (locoregional vs. distant) were not significant, visceral metastases were more common on the second PET scan (8.5% [10/118] vs. 2.2% [62/2832], P = 0.00002). Management change after a second PET scan was less frequent but remained high (46.4% [83/179]), with more frequent change to salvage therapy for extrapelvic metastases (11% [23/210] vs. 7.3% [302/4140], P = 0.0492). Conclusion: More than half of patients with biochemical failure after primary therapy for prostate cancer who have an initial negative PSMA PET/CT scan may have disease identified on a second PSMA PET/CT scan. The impact of a second PSMA PET/CT scan remains high, with management change necessary for nearly 50% of patients. A second PSMA PET/CT scan after an initially negative scan is more likely to be informative among patients with a PSA greater than 0.5 ng/mL or a PSA doubling time of less than 12 mo.