The association of quantitative PSMA PET parameters with pathologic ISUP grade: an international multicenter analysis

Abstract Purpose To assess if PSMA PET quantitative parameters are associated with pathologic ISUP grade group (GG) and upgrading/downgrading. Methods PCa patients undergoing radical prostatectomy with or without pelvic lymph node dissection staged with preoperative PSMA PET at seven referral centres worldwide were evaluated. PSMA PET parameters which included SUV max , PSMA volume , and total PSMA accumulation (PSMA total ) were collected. Multivariable logistic regression evaluated the association between PSMA PET quantified parameters and surgical ISUP GG. Decision-tree analysis was performed to identify discriminative thresholds for all three parameters related to the five ISUP GGs The ROC-derived AUC was used to determine whether the inclusion of PSMA quantified parameters improved the ability of multivariable models to predict ISUP GG ≥ 4. Results A total of 605 patients were included. Overall, 2%, 37%, 37%, 10% and 13% patients had pathologic ISUP GG1, 2, 3, 4, and 5, respectively. At multivariable analyses, all three parameters SUV max , PSMA volume and PSMA total were associated with GG ≥ 4 at surgical pathology after accounting for PSA and clinical T stage based on DRE, hospital and radioligand (all p < 0.05). Addition of all three parameters significantly improved the discrimination of clinical models in predicting GG ≥ 4 from 68% (95%CI 63 – 74) to 74% (95%CI 69 – 79) for SUV max , 72% (95%CI 67 – 76) for PSMA volume , 74% (70 – 79) for PSMA total and 75% (95%CI 71 – 80) when all parameters were included (all p < 0.05). Decision-tree analysis resulted in thresholds that discriminate between GG (SUV max 0–6.5, 6.5–15, 15–28, > 28, PSMA vol 0–2, 2–9, 9–20 and > 20 and PSMA total 0–12, 12–98 and > 98). PSMA volume was significantly associated with GG upgrading (OR 1.03 95%CI 1.01 – 1.05). In patients with biopsy GG1-3, PSMA volume ≥ 2 was significantly associated with higher odds for upgrading to ISUP GG ≥ 4, compared to PSMA volume < 2 (OR 6.36, 95%CI 1.47 – 27.6). Conclusion Quantitative PSMA PET parameters are associated with surgical ISUP GG and upgrading. We propose clinically relevant thresholds of these parameters which can improve in PCa risk stratification in daily clinical practice.