Prostate-specific membrane antigen ligand positron emission tomography (PSMA-PET) disease extent and overall survival (OS) in patients (pts) with high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC): An international multicenter retrospective study.

person Boris A. Hadaschik University of Duisburg-Essen and German Cancer Consortium (DKTK)–University Hospital Essen, Essen, Germany info_outline Boris A. Hadaschik, Matthias Eiber, Manuel Weber, Aravind Ravi Kumar, Jeremie Calais, Johannes Czernin, Harun Ilhan, Fred Saad, Alexander Kretschmer, Sabine D. Brookman-May, Suneel Mundle, Eric Jay Small, Matthew Raymond Smith, Paola M. Perez Rivera, Thomas A. Hope, Ken Herrmann, Michael S Hofman, Wolfgang P. Fendler

Authors person Boris A. Hadaschik University of Duisburg-Essen and German Cancer Consortium (DKTK)–University Hospital Essen, Essen, Germany info_outline Boris A. Hadaschik, Matthias Eiber, Manuel Weber, Aravind Ravi Kumar, Jeremie Calais, Johannes Czernin, Harun Ilhan, Fred Saad, Alexander Kretschmer, Sabine D. Brookman-May, Suneel Mundle, Eric Jay Small, Matthew Raymond Smith, Paola M. Perez Rivera, Thomas A. Hope, Ken Herrmann, Michael S Hofman, Wolfgang P. Fendler Organizations University of Duisburg-Essen and German Cancer Consortium (DKTK)–University Hospital Essen, Essen, Germany, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany, Peter MacCallum Cancer Centre, Melbourne, Australia, UCLA Department of Nuclear Medicine, Los Angeles, CA, University of California Los Angeles, Los Angeles, CA, Ludwig-Maximilians-University, Munich, Germany, Department of Surgery, Université de Montréal, Montréal, QC, Canada, Ludwig-Maximilians-University, Munich, Germany and Janssen Research & Development, Spring House, PA, Janssen Research & Development, Raritan, NJ, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia Abstract Disclosures Research Funding Pharmaceutical/Biotech Company SPARTAN was funded by Janssen Research & Development Background: PSMA-PET was positive for distant metastases (39% distant nodes, 24% bone, 6% visceral organ) in >50% of nmCRPC pts who were nonmetastatic by conventional imaging (Fendler et al. CCR 2019). However, the prognostic impact of PSMA-PET disease extent and its association with oncologic outcomes is unknown. We assessed the prognostic utility of PSMA-PET disease extent in nmCRPC pts defined by conventional imaging for OS and new metastases-free survival (nMFS). Methods: 200 pts (6 centers) with nmCRPC by conventional imaging and prostate-specific antigen doubling time (PSADT) ≤10 mo and/or ISUP grade group ≥4 underwent PSMA-PET. Clinical course and treatment management after PSMA-PET imaging were recorded for 4-9 y. Pt characteristics and PSMA-PET disease extent were analyzed retrospectively. OS and PSMA-PET nMFS (time from primary PSMA-PET to appearance of new distant metastases by PSMA-PET or death) were analyzed for pt subgroups based on disease extent by univariate Cox regression. Results: Median OS was 74 mo, similar to the SPARTAN study of nmCRPC pts (74 mo; Smith et al. Eur Urol 2021). Polymetastatic disease (≥5 distant lesions by PSMA-PET) was associated with shorter OS (median 61 mo vs not reached [NR]) and shorter PSMA-PET nMFS (HR 1.8, 95% CI 1.1-2.9; median 38 vs 60 mo; p=0.021). Any metastatic disease by PSMA-PET and whole-body PSMA tumor volume were not prognostic for OS and PSMA-PET nMFS (all p>0.05). Initial pN1 status was associated with shorter OS (median 55 mo vs NR), but not with PSMA-PET nMFS (p>0.05). Baseline age, baseline Gleason grade ≥8, prior radiotherapy (RT), and PSA and PSADT at time of primary PSMA-PET were not associated with outcomes (all p>0.05). Management after PSMA-PET imaging was mostly local/targeted therapy in pts with no visible/locoregional disease (40/30%) and androgen receptor signaling inhibition therapy in pts with nodal/bone distant metastases (35/43%). Conclusions: Polymetastases (>5) by PSMA-PET and initial pN1 status were significantly associated with worse OS. PSMA-PET disease extent provides a potential novel additional risk stratification for pts with nmCRPC without distant metastasis based on conventional imaging. Further validation is needed to prove its independent prognostic value. Clinical trial information: NCT01946204. Subgroup (N=200) N (%) OS HR (95% CI) p Age <65 y 49 (25) 0.97 (0.52-1.81) 0.92 Gleason grade ≥8 151 (76) 1.41 (1.77-2.58) 0.27 pN1 45 (23) 2.01 (1.17-3.45) 0.012* Prior definitive RT 64 (32) 1.58 (0.93-2.70) 0.092 Prior salvage RT 40 (20) 0.64 (0.31-1.31) 0.22 PSA ≥5.5 mg/dL 97 (49) 1.29 (0.76-2.19) 0.34 PSADT ≤6 85 a (64) 0.87 (0.45-1.66) 0.66 Extrapelvic disease, any 109 (55) 1.41 (0.83-2.40) 0.21 Extrapelvic disease, ≥5 lesions 37 (19) 1.93 (1.08-3.46) 0.027* a n=132, *p<0.05.