Istanbul PSMA PET/CT criteria (IPPC): an imaging-based approach to patient selection for active surveillance

Abstract

Purpose To develop and validate the Istanbul [Ga-68]Ga-PSMA PET/CT Criteria (IPPC), a standardized imaging framework designed to identify clinically significant prostate cancer (csPCa) and improve selection of candidates for active surveillance (AS). Methods [Ga-68]Ga-PSMA PET/CT scans and histopathology from 163 men with biopsy-proven International Society of Urological Pathology (ISUP) Grade Group (GG) 1-2 prostate cancer who underwent radical prostatectomy were retrospectively reviewed by a multidisciplinary panel of nuclear medicine physicians, radiologists, and urologists. Imaging characteristics-including uptake pattern, morphology, localization, and SUVmax-were iteratively analyzed to define three categories: IPPC-1 (indolent), IPPC-2 (indeterminate), and IPPC-3 (csPCa-suspected). Delayed pelvic acquisitions were used as the primary dataset to enhance lesion definition and interpretability. Reproducibility was evaluated in 56 GG1 patients using Cohen's and Fleiss' kappa statistics. Correlations between PSA, SUVmax, and IPPC categories were assessed, and ROC curve analysis was performed to determine the optimal SUVmax threshold for csPCa detection. Results Pathological upgrading occurred in 40% of all cases (74% GG1, 20% GG2). Among 56 GG1 patients, upgrading was 76%. SUVmax and PSA were significantly higher in IPPC-3 than in IPPC-2 (SUVmax 16.3 vs. 6.5, p < 0.001; PSA 7.8 vs. 5.3 ng/mL, p < 0.05). ROC analysis yielded an AUC = 0.76 with an optimal SUVmax cut-off of 8.21 (sensitivity 55%, specificity 90%). All lesions with SUVmax >= 12.0 corresponded to csPCa. Interobserver agreement was substantial (kappa approximate to 0.70-0.74) and intraobserver concordance strong (kappa approximate to 0.80-0.90), confirming high reproducibility. Conclusion IPPC provides a reproducible, biologically grounded method that integrates SUVmax, morphology, and anatomical localization to non-invasively refine AS eligibility. By identifying patients at genuine risk for csPCa while minimizing unnecessary biopsies, IPPC may improve confidence and adherence in AS management. Prospective multicentre validation within the ongoing I-SELECT trial (NCT07168616) will determine its broader clinical applicability.