The prognostic role of 68 Ga-PSMA11 PET-based response in prostate cancer patients undergoing taxane-based chemotherapy.

To assess the prognostic utility of conventional biochemical and imaging response criteria and 68 Ga- prostate-specific membrane antigen (PSMA) 11 PET adapted or specific systems regarding overall survival (OS) in men with metastatic hormone-sensitive (mHSPC) and castration-resistant PC (mCRPC) treated with taxane-based chemotherapy. Methods: A total of 103 patients (pts) ( n = 57 mHSPC, n = 46 mCRPC) underwent taxane-based chemotherapy. All patients had a minimum of two PSMA PET scans (at baseline and up to 3 months post-treatment). PSMA PET response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST 1.1), adapted Prostate Cancer Working Group Criteria 3 (aPCWG3, using PSMA PET instead of bone scan), adapted Positron Emission Tomography Response Criteria in Solid Tumors (aPERCIST) and PSMA PET Progression (PPP) criteria. Response by each criterion was stratified by either progressive disease (PD) versus non-PD. For aPERCIST, stratification by PD, stable disease (SD) and partial/complete remission (PR/CR) was performed. Biochemical response was determined by PSA decline ≥50%. Subgroup analyses were performed by castration-status. Univariable cox proportional hazard regression analyses including Harrell's concordance indices were calculated to investigate the association of PD by response criteria and OS. Kaplan-Meier tests including log-rank statistics were calculated for survival analyses. Results: 26 (25%) of pts had non-measurable disease by RECIST 1.1. PD by any response criterion was associated with an at least 2.5-fold increased risk of death and was highest for PD versus CR/PR by aPERCIST (HR 11.4) on univariable regression. Stratified by castration status, a similar pattern was observed. PD by any criterion as associated with significantly shortened OS across overall and subgroup analyses. PR/CR by aPERCIST identified pts with lower risk of death and longer OS as compared to patients with PD or SD. Conclusion: 68 Ga-PSMA11 PET-based response criteria (PPP, aPERCIST, aPCWG3) have high prognostic utility in men with metastatic PC undergoing taxane-based chemotherapy. PPP is simple to use, identified most patients with PD and showed best prognostic utility regarding OS. PR/CR by aPERCIST identifies a subgroup of responders (PR/CR) showing better outcomes than patients with PD or SD. Future studies are warranted to amend the current paradigm relying on mere differentiation of PD versus non-PD in metastatic PC and to identify true treatment responders by imaging criteria.