PSMA-positive circulating tumor cell detection and outcomes with abiraterone or enzalutamide treatment in men with metastatic castrate resistant prostate cancer.
We conducted a retrospective analysis of the prospective multicenter PROPHECY trial of men with mCRPC (n=118) treated with abiraterone (abi) or enzalutamide (enza).
CTCs were enriched (CTC/mL) and characterized for PSMA protein expression/heterogeneity at baseline and progression. We utilized proportional hazards modeling of the association between PSMA+ CTC enumeration with overall survival(OS) and progression free survival(PFS).
Overall, 97 men with mCRPC had evaluable blood samples for baseline CTC PSMA detection; 78 men (80%) had detectable CTCs. Of these, 55%(43/78) men had any PSMA CTC detection, 21%(16/78) had ≥2 PSMA+ CTCs/mL, and 19%(8/43) were 100% PSMA positive. At progression on abi/enza, 88%(50/57) of men had detectable CTCs, 68%(34/50) had any PSMA CTCs, and 12%(4/34) had 100% PSMA+ CTCs. Among paired cases (n=57), PSMA+ CTC detection increased slightly after abi/enza progression. Using an optimal cut-off of ≥2 PSMA+ CTCs/mL, median OS was 26, 21, and 11 mo for men without CTCs, PSMA- CTCs, and PSMA+ CTCs. Adjusting for prior abi/enza therapy, Halabi clinical risk-score, and CTC enumeration, the hazard ratios for OS and PFS for PSMA+ CTC+ were 3.0 (95% CI=1.1-7.8) and 2.3 (95%CI=0.9-5.8).
We observed PSMA CTC heterogeneity between and within patients with mCRPC over time during abi/enza progression. CTC PSMA enumeration was adversely prognostic independent of clinical factors and disease burden. Further validation is warranted in the context of PSMA-targeted therapies.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2023 Mar 10 [Epub ahead of print]
Santosh Gupta, Susan Halabi, Qian Yang, Akash Roy, Alisa Tubbs, Yamini Gore, Daniel J George, David M Nanus, Emmanuel S Antonarakis, Daniel C Danila, Russell Z Szmulewitz, Richard Wenstrup, Andrew J Armstrong
Epic Sciences, San Diego, CA, United States., Duke Medical Center, Durham, NC, United States., Duke Univ Medical Center, Durham, NC, United States., Duke University, Duke Cancer Institute, Durham, NC, United States., Weill Cornell Medicine, New York, NY, United States., University of Minnesota, Minneapolis, United States., Memorial Sloan Kettering Cancer Center, New York, NY, United States., University of Chicago, Chicago, IL, United States., Duke Cancer Institute, Durham, NC, United States.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/36897758
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