Luminal and basal subtyping of circulating tumor cells and influence on outcomes in patients with metastatic castration-resistant prostate cancer

e17034 Background: Luminal and basal subtyping using PAM50 classifier and the prostate cancer classification system (PCS) have been shown to predict outcomes and treatment response in prostate cancer (PCa). However, these genomic classifiers rely on the acquisition of tumor samples, which are usually not available in patients with metastatic castration resistant PCa (mCRPC). Circulating tumor cells (CTC) are tumors cells shed into bloodstream and can serve as surrogates of tumor. In this study, we aimed to subtype circulating tumor cells with PAM50 and PCS classifiers and evaluate their prognostic performance in mCRPC patients. Methods: A CTC RNA assay was developed by combining NanoVelcro microfluidic system for enriching CTCs and Nanostring nCounter system for PAM50 and PCS profiling of CTCs. The PAM50 and PCS genes were refined through a bioinformatic pipeline to ensure the specific profiling of CTCs. The classification and prognostic performance of the refined CTC-PAM50 and CTC-PCS gene panels were validated in GenomeDx GRID database. For the clinical study, 50 blood samples from mCRPC patients before the initiation of androgen receptor signaling inhibitors (ARSI) (n = 34) or taxanes (n = 16) were analyzed with the CTC RNA assay. Kaplan-Meier analysis and log-rank test were used to evaluate the association between CTC-PAM50/PCS subtypes and survival. Results: The refined CTC-PAM50 (36 genes) and CTC-PCS (40 genes) classifiers retained their original classification and prognostic performance in the GenomeDx GRID cohort. In the clinical study, the CTC RNA assay classified the 50 mCRPC patients into luminal A (n = 14), luminal B (n = 22), and basal (n = 14) by CTC-PAM50 classifier; and PCS1 (n = 5), PCS2 (n = 24), and PCS3 (n = 21) by CTC-PCS classifier. Overall, patients assigned as PCS1 subtype had shorter overall survival than other subtypes (hazard ratio [HR] = 4.8). In addition, basal or PCS1 subtype showed worse biochemical progression free survival than other subtypes (ARSI group: Basal: HR = 2.5; PCS1: HR = 6.9. Taxanes group: Basal: HR = 5.0; PCS1: HR = 7.2). Conclusions: Luminal and basal subtyping of CTCs is prognostic and provides a noninvasive method for molecular profiling mCRPC patients.