Our objective was to develop version 1.0 of a novel framework for response evaluation criteria in prostate-specific membrane antigen (PSMA) PET/CT (RECIP) and a composite response classification that combines responses by prostate-specific antigen (PSA) measurements and by RECIP 1. 0 (PSA + RECIP). Methods: This was an international multicenter, retrospective study. One hundred twenty-four men with metastatic castration-specific prostate cancer (mCRPC) who underwent 177Lu-PSMA therapy and received PSMA PET/CT at baseline and at an interim time point of 12 wk were included. Pairs of baseline interim PET/CT scans were interpreted by consensus among 3 masked 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 included classifications of complete response (RECIP-CR: absence of any PSMA-ligand uptake on interim PET/CT), partial response (RECIP-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), and stable disease (RECIP-SD: any condition but RECIP-PR or RECIP-PD). Changes in PSA levels at 12 wk by Prostate Cancer Working Group Criteria 3 were recorded. PSA + RECIP results were defined as response (PSA decline ≥ 50% or RECIP-PR/CR) or progression (PSA increase ≥ 25% or RECIP-PD). The study's primary outcome measure was the prognostic value of RECIP 1.0 for overall survival (OS). The secondary outcome measure was the prognostic accuracy (C-index) of PSA + RECIP versus PSA responses. Results: Patients with RECIP-PD (n = 39; 8.3 mo) had a shorter OS than patients with stable disease (RECIP-SD) (n = 47; 13.1 mo; P < 0.001) or RECIP-PR (n = 38; 21.7 mo; P < 0.001). In identifying responders and progressors, PSA + RECIP had C-indices superior to those of PSA only: 0.65 versus 0.62 (P = 0.028) and 0.66 versus 0.63 (P = 0.044), respectively. Conclusion: PSMA PET/CT by RECIP 1.0 is prognostic for OS and can be used as a response biomarker to monitor early efficacy of 177Lu-PSMA in men with mCRPC. PSA + RECIP may be used as a novel composite endpoint in mCRPC clinical trial design.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2022 Apr 14 [Epub]
Andrei Gafita, Isabel Rauscher, Manuel Weber, Boris Hadaschik, Hui Wang, Wesley R Armstrong, Robert Tauber, Tristan R Grogan, Johannes Czernin, Matthew B Rettig, Ken Herrmann, Jeremie Calais, Wolfgang A Weber, Matthias R Benz, Wolfgang P Fendler, Matthias Eiber
Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, California; ., Department of Nuclear Medicine, Technical University Munich, Klinikum rechts der Isar, Munich, Germany., Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium-University Hospital Essen, Essen, Germany., Department of Urology, University of Duisburg-Essen and German Cancer Consortium-University Hospital Essen, Essen, Germany., Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, California., Department of Urology, Technical University Munich, Klinikum rechts der Isar, Munich, Germany., Department of Medicine Statistics Core, David Geffen School of Medicine, UCLA, Los Angeles, California; and., Department of Urology, David Geffen School of Medicine, UCLA, Los Angeles, California.