Prognostic value of tumor volume assessment on PSMA PET after 177 Lu-PSMA radioligand therapy evaluated by PSMA PET/CT consensus statement and RECIP 1.0.

Introduction: Quantitative evaluation of prostate-specific membrane antigen (PSMA)- targeting positron emission tomography/computer tomography (PSMA PET/CT) remains challenging but is urgently needed for the use of standardized PET-based response criteria, such as the PSMA PET/CT consensus statement or RECIP 1.0. A recent study evaluated the prognostic value of whole-body tumor volume using a semiautomatical method relying on a 50% threshold of maximum lesion standardized uptake value (PSMA TV50 ). In the present study, we analyzed the suitability of this approach comparing 18 F-PSMA-1007 to 68 Ga-PSMA-11 PET/CT scans and the potential of PSMA TV50 for the prediction of overall survival (OS) in patients before 177 Lu-PSMA-radioligand therapy (PSMA RLT). Moreover, PSMA TV50 was integrated into the PSMA PET/CT consensus statement as well as RECIP 1.0 and the prognostic value of these response classification systems was compared. Methods: This retrospective study included 70 patients with metastatic castration-resistant prostate cancer undergoing PSMA RLT. 33 patients were monitored by 68 Ga-PSMA-11 PET/CT and 37 patients by 18 F-PSMA-1007 PET/CT. PET/CT scans before (baseline) and at the end of PSMA RLT after 2-4 cycles (follow-up) were separately analyzed by two readers. PSMA TV50 at baseline and its change to follow-up (ΔPSMA TV50 ; expressed as a ratio) were correlated with OS using Cox proportional hazard regression. The results of both subgroups were compared. The integration of ΔPSMA TV50 in existing response classification systems was evaluated. To assess and compare the discriminatory strength of these classification systems, Gönen & Heller concordance probability estimates (CPE) were calculated. Results: PSMA TV50 -determination was technically feasible in all examinations. A higher PSMA TV50 at baseline and a higher ΔPSMA TV50 were strongly associated with a shorter OS for both 68 Ga-PSMA-11 (PSMA TV50 : HR 1.29 [1.05 - 1.55], p=0.009; ΔPSMA TV50 : HR 1.83 [1.08 - 3.09], p=0.024) and 18 F-PSMA-1007 (PSMA TV50 : HR 1.84 [1.13 - 2.99], p=0.014; ΔPSMA TV50 : HR 1.23 [1.04 - 1.51], p=0.03). Response assessment provided high discriminatory power for OS for the PSMA PET/CT consensus statement (CPE 0.73) as well as RECIP 1.0 (CPE 0.74). Conclusion: PSMA TV50 and ΔPSMA TV50 proved to be predictive of OS not only for 68 Ga-PSMA-11 but also for 18 F-PSMA-1007 PET/CT scans. Subsequent integration of ΔPSMA TV50 into the PSMA PET/CT consensus statement and RECIP 1.0 provided equally high prognostic value for both classification systems.