Although tumor volume and new lesions (NLs) have been investigated previously as measures of response, the clinical impact of changes in tumor uptake on prostate-specific membrane antigen (PSMA) PET remains largely unknown. Methods: This multicenter retrospective study investigated the clinical impact of changes in tumor uptake and volume on PSMA PET during [177Lu]Lu-PSMA in metastatic castration-resistant prostate cancer (mCRPC). The primary outcomes were the associations of changes in SUVmax (ΔSUVmax) and SUVmean (ΔSUVmean), changes in total tumor volume (ΔTTV), and occurrence of NLs with prostate-specific antigen (PSA) progression-free survival (PSA-PFS) and overall survival (OS). The study included patients with mCRPC who received [177Lu]Lu-PSMA between 2014 and 2019. PSMA PET/CT was performed at baseline and after 2 cycles of therapy. Whole-body analyses (SUVmax, SUVmean, TTV, and NLs) were performed and calculated using qPSMA software. Results: In total, 124 patients with mCRPC (median age, 73 y; interquartile range, 67-76 y) were included in the study. Whole-body ΔTTV and the occurrence of NLs were significantly associated with shorter PSA-PFS (hazard ratio [HR], 5.7; 95% CI, 3.59-9.06; and HR, 1.6; 95% CI, 1.4-1.8; P < 0.0001) and with OS (HR, 2.3; 95% CI, 1.61-3.43; and HR, 1.3; 95% CI, 1.1-1.4; P < 0.001). Patient-based analysis showed that ΔSUVmax and ΔSUVmean were not associated with outcome (HR, 1.00; 95% CI, 0.99-1.00; P = 0.30; and HR, 0.90; 95% CI, 0.99-1.00; P = 0.11). Region-based analysis found that only ΔSUVmax in visceral lesions was significantly associated with PSA-PFS (P = 0.007) but not with OS. Conclusion: Only ΔTTV and the occurrence of NLs provided significant prognostic value and should be considered when evaluating treatment response to [177Lu]Lu-PSMA therapy.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2025 Oct 30 [Epub ahead of print]
Loïc Djaileb, Andrea Farolfi, Isabel Rauscher, Mahan Haghighatian, Alexis Mercier, Wolfgang P Fendler, Boris Hadaschik, Ken Herrmann, Lilja B Solnes, Matthew Rettig, Manuel Weber, Johannes Czernin, Jeremie Calais, Matthias R Benz, Matthias Eiber, Andrei Gafita
Nuclear Medicine Department, LRB, Université Grenoble Alpes, INSERM, CHU Grenoble Alpes, Grenoble, France; ., Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Department of Nuclear Medicine, Technical University Munich, Klinikum rechts der Isar, Munich, Germany., Division of Nuclear Medicine and Molecular Imaging, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland., Nuclear Medicine Department, LRB, Université Grenoble Alpes, INSERM, CHU Grenoble Alpes, Grenoble, France., Department of Nuclear Medicine, University Hospital Essen, German Cancer Consortium, West German Cancer Center, Essen, Germany., Department of Urology, University of Duisburg-Essen, and German Cancer Consortium-University Hospital Essen, Essen, Germany., Department of Urology, David Geffen School of Medicine, UCLA, and VA Greater Los Angeles, Los Angeles, California; and., Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, California.