Simple SummaryAfter radical prostatectomy (RP), about a third of patients present with BCR. The European Association of Urology (EAU) biochemical recurrence (BCR) risk grouping relies on data from historical cohorts that used conventional imaging techniques. Given the importance of differentiating the recurrence patterns and their impact on treatment decisions, the indication for PSMA PET/CT has been established in BCR prostate cancer. The main aim of this study was to study the positivity rate of68Ga-PSMA-11 PET/CT across BCR low and high-risk groups and to establish positivity predictors. We found a higher rate of positivity within the BCR high-risk group, whereas more local and oligometastatic recurrences were objectified in BCR low-risk group. This raises the discussion for including PSMA PET/CT within the risk stratification after carefully evaluating positivity predictive factors. Future studies are needed to confirm the above findings for better patient selection and management.Abstract(1) Background: The European Association of Urology (EAU) biochemical recurrence (BCR) risk grouping relies on data from historical cohorts that used conventional imaging techniques. In the era of PSMA PET/CT, we compared the patterns of positivity in the two risk groups and provided insight into positivity predictive factors. (2) Methods: Data from 1185 patients who underwent68Ga-PSMA-11PET/CT for BCR was analyzed, out of which 435 patients treated initially treated by radical prostatectomy were included in the final analysis. (3) Results: A significantly higher rate of positivity in the BCR high-risk group was observed (59% vs. 36%,p< 0.001). BCR low-risk group demonstrated more local (26% vs. 6%,p< 0.001) and oligometastatic (100% vs. 81%,p< 0.001) recurrences. The BCR risk group and PSA level at the time of PSMA PET/CT were independent predictive factors of positivity. (4) Conclusions: This study confirms that the EAU BCR risk groups have different rates of PSMA PET/CT positivity. Even with a lower rate in the BCR low-risk group, oligometastatic disease was 100% in those with distant metastases. Given the presence of discordant positivity and risk classification, integrating PSMA PET/CT positivity predictors into risk calculators for BCR might improve patient classification for subsequent treatment options. Future prospective studies are still needed to validate the above findings and assumptions.