Abstract 3690: Monitoring prostate specific membrane antigen or androgen receptor expression on circulating stromal cells in advanced prostate cancer patients and their correlation with patient response
Authors: Dimpal M. Kasabwala, Raymond C. Bergan, R. Katherine Alpaugh, Daniel C. Danila, Tuan L. Chuang, Brenda Y. Hurtado, Daniel L. Adams
Journal: Cancer Research (2024)

Abstract Background: Metastatic Prostate cancer (mPCa) mortality rates are high despite numerous treatment options against various mechanisms of action, including targeted therapies, i.e. prostate specific membrane antigen (PSMA)-targeted therapy (Pluvicto) or anti-androgen receptor (AR) (Enzulamide, Biculamide). Further, tumor biomarkers (i.e. PSMA and AR) can change over time and with resistance mechanisms that develop after treatments. This suggests that primary biopsies may not represent later PCa tumors necessitating a way to identify patients that may respond to later line therapies. Blood based biopsies can be used to monitor PCa treatment, which can include circulating tumor cells (CTCs) and the newly discovered cancer associated macrophage like cells (CAMLs), a cancer specific circulating phagocytic stromal cells. Interestingly, while PSMA &amp; AR have been identified in CTCs, they have not been evaluated in CAMLs, nor have PSMA &amp; AR expressions in CTCs &amp; CAMLs been evaluated in anti-AR therapy settings. We measured CAMLs &amp; CTCs in mPCa to evaluate their PSMA &amp; AR expression, including in patients treated with anti-AR therapy. Methods: We evaluated CAMLs &amp; CTCs in a multi-institutional prospective pilot study using n=30 mPCa patients with progressive disease, prior to starting a new line of therapy (T0). Whole peripheral blood (7.5mL) was filtered for CAMLs &amp; CTCs and stained for PSMA (n=15) &amp; AR (n=15). In addition, 15 patients were treated with anti-AR therapy as standard of care and responses by PET/CT were compared against AR expression. When possible, follow up samples (T1) were also procured. Results: CTCs were identified in 16% (n=5/30) of patients and CAMLs were identified in 96% (n=29/30), with 53% of patients having hyperengorged CAMLs ≥50 μm (n=16/30). CTCs in patients were not statistically significant for worse outcomes PFS HR= 0.1748, p=0.546 nor OS (HR= 1.303, p=0.865), nor were CAMLs prognostic for PFS or OS. However, patients with ≥50 μm CAMLs did have significantly worse PFS (HR= 5.9, CI95% 2.2-16.3, p=0.001) and worse OS (HR= 3.1, CI95% 1.3-7.1, p=0.016). Further, PSMA CAML/CTC expression was high in 60% (n=9/15) of patients and AR CAML/CTC expression was high in 53% (n=8/15). Of the n=15 patients who received anti-AR therapy after T0, high AR expressing CAMLs/CTCs (n=8/15) had a ~250% better mPFS of 10.3 months (mons) (progressing at 2.2-32.6 mons) vs low AR CAMLs/CTCs mPFS of 4 mons (progressing at 0.2-7.2 mons). Additional mOS analysis from T1 samples and 2-year survival is ongoing. Conclusion: We utilized liquid biopsies to monitor the expression of two common cell surface receptors (PSMA &amp; AR) in CAMLs and CTCs in mPCa. Further, in a small subset of patients treated with AR therapy, high AR CTC/CAML expression appeared to correlate with better response rates, though larger prospective studies are needed. Citation Format: Dimpal M. Kasabwala, Raymond C. Bergan, R. Katherine Alpaugh, Daniel C. Danila, Tuan L. Chuang, Brenda Y. Hurtado, Daniel L. Adams. Monitoring prostate specific membrane antigen or androgen receptor expression on circulating stromal cells in advanced prostate cancer patients and their correlation with patient response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3690.