Prognostic Value of Tumor Volume Assessment on PSMA PET After 177Lu-PSMA Radioligand Therapy Evaluated by PSMA PET/CT Consensus Statement and RECIP 1.0

Abstract

Quantitative evaluation of prostate-specific membrane antigen (PSMA)-targeting 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 Response Evaluation Criteria in PSMA PET/CT (RECIP 1.0). A recent study evaluated the prognostic value of whole-body tumor volume using a semiautomatic method relying on a 50% threshold of lesion SUV_max (PSMA_TV50). In the present study, we analyzed the suitability of this approach comparing ¹⁸F-PSMA-1007 with ⁶⁸Ga-PSMA-11 PET/CT scans and the potential of PSMA_TV50 for the prediction of overall survival (OS) in patients before ¹⁷⁷Lu-PSMA radioligand therapy (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. Thirty-three patients were monitored by ⁶⁸Ga-PSMA-11 PET/CT, and 37 patients by ¹⁸F-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 2 readers. PSMA_TV50 at baseline and its change at the time of follow-up (ΔPSMA_TV50, expressed as a ratio) were correlated with OS using Cox proportional-hazards 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 and Heller concordance probability estimates 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 ⁶⁸Ga-PSMA-11 (PSMA_TV50: hazard ratio [HR] of 1.29 [95% CI, 1.05-1.55], P = 0.009; ΔPSMA_TV50: HR of 1.83 [95% CI, 1.08-3.09], P = 0.024) and ¹⁸F-PSMA-1007 (PSMA_TV50: HR of 1.84 [95% CI, 1.13-2.99], P = 0.014; ΔPSMA_TV50: HR of 1.23 [95% CI, 1.04-1.51], P = 0.03). Response assessment provided high discriminatory power for OS for the PSMA PET/CT consensus statement (concordance probability estimate, 0.73) as well as RECIP 1.0 (concordance probability estimate, 0.74). Conclusion: PSMA_TV50 and ΔPSMA_TV50 proved to be predictive of OS not only for ⁶⁸Ga-PSMA-11 but also for ¹⁸F-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.

Keywords: PSMA PET/CT; PSMATV50; RECIP 1.0; radioligand therapy; response assessment.