Circulating Tumor Cells and Clinical Outcomes in Men with Metastatic Castration-sensitive Prostate Cancer Treated with Enzalutamide and Docetaxel: An Analysis of the ENZADA Trial

恩扎卢胺联合多西他赛治疗转移性去势敏感性前列腺癌患者的循环肿瘤细胞与临床结局:ENZADA试验分析

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Abstract

We evaluated the prognostic value of circulating tumor cell (CTC) counts and androgen receptor splice variant 7 (AR-V7) status at baseline and after docetaxel in the previously published ENZADA trial. We analyzed data for 35 participants with both baseline and postdocetaxel CTC counts. CTC count status at two thresholds (≥2 vs <2 cells/μl; ≥3 vs <3 cells/μl) was not prognostic for a 26-wk or 52-wk prostate-specific antigen (PSA) complete response (CR), overall survival (OS), or time to castration resistance (TTCR). CTC count status (>0 vs 0 cells/μl) after docetaxel was not associated with 26-wk PSA CR, OS, or TTCR. However, there was a trend towards a higher 52-wk PSA CR rate among those with detectable CTCs after docetaxel (92% vs 52%; p = 0.03). A binary variable indicating the change in CTC level (increased or remained stable/decreased) from baseline after docetaxel was also not associated with OS, TTCR, or landmark 26-wk or 52-wk PSA CR rates. However, in the group with 52-wk PSA CR data, a rise in postdocetaxel CTC level was associated with shorter TTCR (hazard ratio [HR] 9.8, 95% confidence interval [CI] 1.1-88.1) and a trend towards shorter OS (HR 7.3, 95% CI 0.76-70.6). AR-V7 was only detected in one patient at each time point. The CTC count was not prognostic for patients with metastatic hormone-sensitive prostate cancer treated with chemohormonal therapy in this small cohort, although a rise in CTC count after docetaxel may identify patients at high risk of progression among those with a PSA CR. PATIENT SUMMARY: For men with metastatic prostate cancer treated with hormone therapies and chemotherapy, we looked at whether the level of tumor cells circulating in the blood (CTCs) was associated with the PSA (prostate-specific antigen) response and survival time. The CTC level was checked before treatment and after six doses of chemotherapy. We found no association with prostate cancer outcomes. However, in the group of patients whose PSA became undetectable after treatment, a CTC increase after chemotherapy identified men with a higher risk of cancer progression and death.

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