To improve [177Lu]Lu-Prostate-specific membrane antigen therapy (LuPSMA) selection, this study investigates the prognostic value of PSMA and 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG)-PET in metastatic castration-resistant prostate cancer (mCRPC) patients considered for LuPSMA therapy.
We conducted a retrospective analysis in 152 mCRPC patients referred for LuPSMA therapy who underwent PSMA and [18F]FDG-PET/CT. Of these, 104 patients (68.4%) underwent LuPSMA therapy, while 48 (31.6%) received other standard of care (SOC). PET/CT analyses included visual assessment and semiquantitative measurements. Clinical and laboratory parameters were recorded. Overall survival (OS) and PSA response (decline > 50%) were primary and secondary endpoints, respectively.
Baseline [18F]FDG-derived total tumor volume was the only independent predictor of overall survival both in patients subsequently treated with LuPSMA (HR 1.28 [95%CI 1.02-1.61]; p = 0.03) or in those under other SOC (HR 1.61 [95%CI 1.02-2.56]; p = 0.04), respectively. In other SOC patients, additional independent predictors of OS were total lesion PSMA uptake (PSMA-TL; HR 1.14 [95%CI 1.03-1.26]; p = 0.01), [18F]FDG mean SUV (HR 20.88 [95%CI 1.2-364.74]; p = 0.04), and [18F]FDG total lesion glycolysis (HR 1.61 [95%CI 1.02-2.56]; p = 0.04). In LuPSMA patients, PSMA-PET SUVmean was a significant independent predictor of PSA decline ≥ 50% (OR 2.97 [95%CI 1.27-8.16]; p = 0.02).
PSMA-PET and [18F]FDG-PET provide imaging biomarkers of outcome in candidates for LuPSMA. FDG-PET total tumor volume was an independent predictor of overall survival in candidates for LuPSMA therapy, irrespective of subsequent treatment decision. PSMA-PET SUVmean was associated with biochemical response to LuPSMA. Dual tracer imaging should further be assessed in prospective trials for mCRPC treatment guidance.
European journal of nuclear medicine and molecular imaging. 2025 Mar 21 [Epub ahead of print]
Tugce Telli, Leonor Lopes, Madeleine Karpinski, Kim M Pabst, Viktor Grünwald, Kuangyu Shi, Boris Hadaschik, Claudia Kesch, Lale Umutlu, Ken Herrmann, Robert Seifert, Wolfgang P Fendler
Department of Nuclear Medicine, University Hospital Essen, Essen, Germany. ., Department of Nuclear Medicine, University Hospital Bern, Bern, Switzerland., Department of Nuclear Medicine, University Hospital Essen, Essen, Germany., German Cancer Consortium (DKTK), Partner Site, Partnership Between DKFZ and University Hospital Essenaq , Essen, Germany.