| Abstract: |
Purpose: HOXB13 is an androgen receptor (AR) coregulator specifically expressed in cells of prostatic lineage. We sought to associate circulating tumor cell (CTC) HOXB13 expression with outcomes in men with mCRPC treated with abiraterone or enzalutamide. Experimental Design: We conducted a retrospective analysis of the multicenter prospective PROPHECY trial of mCRPC men (NCT02269982, n 1⁄4 118) treated with abiraterone/enzalutamide. CTC detection and HOXB13 complementary DNA (cDNA) expression was measured using a modified Adnatest, grouping patients into 3 categories: CTC 0 (undetectable); CTCþ HOXB13 CTC low (<4 copies); or CTCþ HOXB13 CTC high. The HOXB13 threshold was determined by maximally selected rank statistics for prognostic associations with overall survival (OS) and progression-free survival (PFS). Results: We included 102 men with sufficient CTC HOXB13 cDNA, identifying 25%, 31%, and 44% of patients who were CTC 0, CTCþ HOXB13 low, and CTCþ HOXB13 high, respectively. Median OS were 25.7, 27.8, and 12.1 months whereas the median PFS were 9.0, 7.7, and 3.8 months, respectively. In subgroup analysis among men with CellSearch CTCs ≥5 copies/mL and adjusting for prior abi/enza treatment and Halabi clinical risk score, the multivariate HR for HOXB13 CTC detection was 2.39 (95% CI, 1.06–5.40) for OS and 2.78 (95% CI, 1.38–5.59) for PFS, respectively. Low HOXB13 CTC detection was associated with lower CTC PSA, PSMA, AR-FL, and AR-V7 detection, and more liver/lung metastases (41% vs. 25%). Conclusions: Higher CTC HOXB13 expression is associated with AR-dependent biomarkers in CTCs and is adversely prognostic in the context of potent AR inhibition in men with mCRPC. © 2024 American Association for Cancer Research Inc.. All rights reserved. |
| Keywords: |
retrospective studies; genetics; clinical trial; prospective study; prospective studies; metabolism; homeodomain proteins; pathology; retrospective study; tumor marker; rna; neoplastic cells, circulating; multicenter study; androgen receptor; receptors, androgen; homeodomain protein; tumor embolism; nitriles; nitrile; complementary dna; dna, complementary; castration resistant prostate cancer; phenylthiohydantoin; benzamide derivative; benzamides; abiraterone; enzalutamide; humans; human; male; prostatic neoplasms, castration-resistant; androstane derivative; biomarkers, tumor; androstenes; hoxb13 protein, human
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