Correlation of baseline circulating tumor cells (CTC) and associated genomic profile with survival outcomes in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) in a real-world cohort.

Abstract

5077 Background: We recently published, in the context of SWOG1216 trial in pts with mCSPC, that higher baseline CTC level were associated with inferior survival outcomes (Goldkorn. Agarwal, CCR, 2021). Here in, we validate these findings in a real world population of mCSPC and interrogate tumor genomic profile with respect to the CTC level. Methods: Eligibility criteria: new mCSPC receiving ADT without or with intensification (docetaxel or novel hormonal therapy) and enumeration of baseline CTCs by FDA cleared Cell Search CTC assay. Gene alterations were determined by comprehensive genomic profiling (CGP) of tumor tissue (Foundation Medicine). CTC counts were categorized as 0, 1-4 and ≥5/7.5 ml. Relationships between CTC counts and number (no.) of genes altered and individual gene alterations were assessed via Kruskal-Wallis and chi-squared tests, respectively. Relationships between progression-free survival (PFS), overall survival (OS) and individual mutations were assessed via log-rank tests. Relationships between CTC counts, PFS and OS were assessed by Cox proportional hazards models, both unadjusted and adjusted for multiple variables (Table). Results: Overall 103 pts were eligible. Median age: 67 yrs, Gleason score: 9, PSA at ADT initiation: 41 ng/mL. 67 (65%) pts had de-novo metastatic disease and 44 (43%) pts underwent ADT intensification therapy. Pts with greater CTC counts tended to have greater no. of altered genes (p=0.017), greater no. of total alterations (p=0.017) and higher rate of TP53 mutations (p=0.036). In univariate analyses (UVA) and multivariable analyses (MVA), both CTC counts and no. of genes altered were strongly associated with both PFS and OS (Table). CGP of tumors with respect to CTC counts will be presented in meeting. Conclusions: Herein, we validate our previous findings from SWOG1216 trial of association of higher CTC level with inferior survival outcomes in a real world mCSPC cohort. The CTC enriched population is associated with a distinct tumor genomic landscape, which may guide further drug development in this pt population at the highest risk of progression and/or death.[Table: see text]