Novel framework for treatment response evaluation using PSMA-PET/CT in patients with metastatic castration-resistant prostate cancer (RECIP 1.0): an international multicenter study

Purpose: To develop a novel framework for Response Evaluation Criteria In PSMA-PET/CT (RECIP) 1.0 and a composite response classification which combines responses by PSA measurements and by RECIP 1.0 (PSA+RECIP). Methods: This was an international, multicenter, retrospective study. 124 men with mCRPC who underwent ¹⁷⁷Lu-PSMA therapy and received PSMA-PET/CT at baseline (bPET) and at interim at 12 weeks (iPET) were included. Pairs of bPET and iPET were interpreted by consensus among three blinded readers for appearance of new lesions. Tumor lesions were segmented and total PSMA-positive tumor volume (PSMA-VOL) was obtained. Appearance of new lesions and changes in PSMA-VOL were combined to develop RECIP 1.0, which was defined as: complete response (RECIP-CR: absence of any PSMA-ligand uptake on iPET), partial response (PSMA-PR: decline ≥30% in PSMA-VOL and no appearance of new lesions), progressive disease (RECIP-PD: increase ≥20% in PSMA-VOL and appearance of new lesions), stable disease (RECIP-SD: any condition but RECIP-PR or RECIP-PD). Changes in PSA levels at 12 weeks by PCWG3 were recorded. Responses by PSA+RECIP were defined as: response (PSA decline ≥50% or RECIP-PR/CR) and progression (PSA increase ≥25% or RECIP-PD). Study9s primary outcome measure was the prognostic value of RECIP 1.0 for overall survival (OS). Secondary outcome measure was the prognostic accuracy (C-index) of PSA+RECIP vs PSA responses. Results: Patients with progressive disease (RECIP-PD; n = 39; 8.3 mo) had shorter OS compared to patients with stable disease (RECIP-SD; n = 47; 13.1 mo; p<0.001) and to those with partial response (RECIP-PR; n = 38; 21.7 mo; p<0.001). PSA+RECIP had superior C-indices in identifying responders and progressors compared to PSA only: 0.65 vs 0.62 (P = 0.028) and 0.66 vs 0.63 (P = 0.044), respectively. Conclusion: PSMA-PET/CT by RECIP 1.0 is prognostic for OS and can be used as an early response biomarker to monitor efficacy of ¹⁷⁷Lu-PSMA in men with mCRPC. PSA+RECIP may be used as a novel composite endpoint in mCRPC clinical trial design.