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Abstract PurposeProstate-specific membrane antigen (PSMA) -based images, which visually quantify PSMA expression, are used to determine prostate cancer (PCa) micrometastases. This study evaluated whether a circulating tumor cell (CTCs-based transcript platform, including PSMA mRNA, could help identify potential prognostic markers in PCa. Experimental design We prospectively enrolled 21 healthy individuals and 247 patients with PCa (localized PCa LPCa: 94; metastatic hormone-sensitive PCa mHSPC: 44; and metastatic castration-resistant PCa mCRPC: 109). The mRNA expression of six transcripts (PSMA, prostate-specific antigen PSA, AR, AR-V7, EpCAM, and KRT 19) from CTCs was measured, and their relationship with biochemical recurrence (BCR) in LPCa and mCRPC progression-free survival (PFS) rate in mHSPC was assessed. PSA-PFS and radiological-PFS were also calculated to identify potential biomarkers for predicting androgen receptor signaling inhibitor (ARSI) and taxane-based chemotherapy resistance in mCRPC. Results CTC detection rates were 75. 5%, 95. 3%, and 98% for LPCa, mHSPC, and mCRPC, respectively. In LPCa, PSMA (hazard ratio HR: 3. 35; P=0. 028) and PSA mRNA (HR: 1. 42; P=0. 047) expression was associated with BCR. mHSPC patients with high PSMA (HR: 4. 26; P=0. 020) and PSA mRNA (HR: 3. 52; P=0. 042) expression showed significantly worse mCRPC-PFS rates than those with low expression. Increased PSA and PSMA mRNA expression was significantly associated with shorter PSA-PFS and radiological PFS in mCPRC, indicating an association with drug resistance. Conclusion PSMA and PSA mRNA expression is associated with BCR in LPCa. In advanced PCa, PSMA and PSA mRNA can also predict rapid progression from mHSPC to mCRPC and ARSI or taxane-based chemotherapy resistance. Citation Format: Hyungseok Cho, Seok-Soo Byun, Nak-Hoon Son, Jae Il Chung, Won Ik Seo, Chan Ho Lee, Todd M Morgan, Ki-Ho Han, Jae-Seung Chung. Impact of circulating tumor cell-expressed prostate-specific membrane antigen and prostate-specific antigen transcripts in various stages of prostate cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (7Suppl): Abstract nr LB110.
Cho et al. (2024) studied this question.