GATA6 Alteration as a Potential Prognostic Biomarker in Castration-Resistant Prostate Cancer Treated With Docetaxel After Androgen Receptor Pathway Inhibitor Failure

Purpose: This study aimed to evaluate the prognostic significance of GATA6 alterations in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving docetaxel after androgen receptor pathway inhibitor (ARPI) failure.Materials and Methods: In this retrospective exploratory cohort study, patients with mCRPC who received docetaxel after prior ARPI therapy were included. Clinical and genomic data were reviewed, and Cox proportional hazards models were used to evaluate the prognostic impact of genomic alterations present in ≥5% of the cohort.Results: A total of 90 patients were analyzed (median age, 70.5 years; median follow-up, 17.7 months). GATA6 alteration was identified in 5 patients (5.6% of the cohort). In the gene-only analysis, GATA6 alteration was associated with shorter radiographic progression-free survival (rPFS) in both univariate (hazard ratio [HR], 7.44; 95% confidence interval [CI], 2.72–20.33; p<0.001) and multivariate models (HR, 5.15; 95% CI, 1.70–15.62; p=0.004). After adjustment for relevant clinical variables, GATA6 alteration remained significantly associated with shorter rPFS (HR, 7.38; 95% CI, 2.61–20.91; p<0.001). Kaplan-Meier analysis also showed shorter rPFS in patients with GATA6 alterations (log-rank p=0.005). GATA6 alteration was also associated with shorter prostate-specific antigen progression-free survival (PSA-PFS) in Cox analysis (HR, 7.37; p<0.001), and Kaplan- Meier analysis showed shorter PSA-PFS (log-rank p=0.037). For overall survival, GATA6 alteration showed a nonsignificant trend (HR, 2.15; p=0.106).Conclusion: GATA6 alteration was associated with shorter rPFS and PSA-PFS in this cohort and may be aprognostic biomarker of poor outcomes in patients receiving docetaxel after ARPI therapy. Further studiesare needed to validate these findings.