Combined analysis of circulating tumor cells and PSMA imaging metrics to predict efficacy of 177 Lu-PSMA-617 in metastatic prostate cancer.

• DOI: 10.1200/jco.2025.43.5_suppl.215
• Publication Date: 2025-02-18T14:42:46Z
• Authors: Yoshiyuki Miyazawa; Arda Könik; Zoe Guan; Ibrahim Chamseddine; Keisuke Otani; Yukako S Otani; Rea Pittie; Ella Chung; Daniel J Rodden; Linda Nieman; Katherine Huang Xu; Mythreayi Shan; Richard J. Lee; Xin Gao; Pedram Heidari; Dejan Juric; Miles A Miller; Thomas SC Ng; David T Miyamoto
• Keywords: Circulating tumor cell; Glutamate carboxypeptidase II

215 Background: Radioligand therapy targeting prostate-specific membrane antigen (PSMA), such as 177 Lu-PSMA-617, has demonstrated clinical efficacy in PSMA-PET-positive metastatic castration-resistant prostate cancer (mCRPC). However, not all PSMA-positive mCRPC patients benefit from this therapy, highlighting the need for novel biomarkers to predict treatment response. We aimed evaluate whether molecular analysis of circulating tumor cells (CTCs) could provide predictive Lu-PSMA-617 therapy. Methods: In single-institution biomarker study, male with scheduled begin were enrolled. Informed consent was obtained (DF-HCC 13-416). CTCs isolated blood samples collected prior initiation using a microfluidic device (CTC-iChip). Half each patient immunostained antibodies against cytokeratin, EpCAM, and PSMA counterstained CD45 exclude leukocytes. The stained imaged Vectra Polaris multispectral microscope. fluorescence intensity CTC categorized into four levels (3+, 2+, 1+, 0). remaining analyzed droplet digital polymerase chain reaction (ddPCR) profile expression genes, androgen receptor splice variant AR-V7 , neuroendocrine genes. analyses pre-treatment PSMA-PET imaging metrics compared outcomes. Radiographic progression-free survival (rPFS) evaluated Kaplan-Meier log-rank tests. Results: Blood 24 enrolled analyzed, median follow-up 7.5 months. Median age 71.5 years (range 53-83). count 5.9 cells/7.5mL blood. Patients high (>5.85 cells/7.5 mL) presence PSMA-negative had worse rPFS others, although difference statistically significant (median 86 vs. 393 days, p = 0.0840). who -positive before significantly shorter -negative 67 0.0031). Additionally, DLL3 than 109 days 402 0.0348). Using machine learning, model developed incorporating following factors: mean SUV, CHGA ARV7 STEAP2 AGR2 E2F1 . This accuracy outcomes (Low-risk group: 447 High-risk 0.0002). Conclusions: combination PET may be useful predicting therapeutic ¹⁷⁷Lu-PSMA-617 treatment, warrants validation additional cohorts.