Abstract
Objective: We examined whether epidermal growth factor receptor (EGFR) expression in circulating tumor cells (CTCs) can be used to predict survival in a population of bone-metastatic castration-resistant prostate cancer (mCRPC) patients treated with docetaxel chemotherapy. Methods: All patients with mCRPC who had experienced treatment failure with androgen-deprivation therapy and had received docetaxel chemotherapy were eligible. CTCs and EGFR expression in CTCs were enumerated with the CellSearch System in whole blood. This system is a semi-automated system that detects and enriches epithelial cells from whole blood using an EpCAM antibody-based immunomagnetic capture. In addition, the EGFR-positive CTCs were assessed using CellSearch® Tumor Phenotyping Reagent EGFR. Results: The median CTC count at baseline before starting trial treatment was eight CTCs per 7.5 mL of blood (range 0–184). There were 37 patients (61.7%) who had ≥5 CTCs, with median overall survival of 11.5 months compared with 20.0 months for 23 patients (38.3%) with <5 CTCs (p < 0.001). A total of 15 patients (40.5%, 15/37) with five or more CTCs were subjected to automated immunofluorescence staining and cell sorting for EGFR protein. Patients with EGFR-positive CTCs had a shorter overall survival (OS) (5.5 months) than patients with EGFR-negative CTCs (20.0 months). CTCs, EGFR-positive CTCs, and alkaline phosphatase (ALP) were independent predictors of overall survival time (p = 0.002, p < 0.001, and p = 0.017, respectively). Conclusion: CTCs may be an independent predictor of OS in CRPC treated with docetaxel chemotherapy. The EGFR expression detected in CTCs was important for assessing the response to chemotherapy and predicting disease outcome.
Highlights
Castration-resistant prostate cancer (CRPC) is a complex process involving many different signal transduction pathways
Multivariate analysis demonstrated that higher circulating tumor cells (CTCs) counts were associated with: alkaline phosphatase (ALP) > upper normal limit (UNL) (p = 0.002), hemoglobin level of 30 ng/mL (p = 0.042) extent of disease (EOD) > 3 (p = 0.003), and a Gleason score >9 (p = 0.021)
We examined the usefulness of CTCs for predicting survival in 60 CRPC patients treated with docetaxel chemotherapy
Summary
Castration-resistant prostate cancer (CRPC) is a complex process involving many different signal transduction pathways. The epidermal growth factor receptor (EGFR) has been reported to provide an important mechanism for the progression of CRPC [1,2]. Hyperactivity of EGFR is related to androgen independence of prostate cancer cells. Levels of EGFR immunoreactivity were increased in hormone-independent human prostate cancer cell lines [3,4]. Several groups have reported that the number and characteristics of circulating tumor cells (CTCs) in cancer patients are parallel to tumor progression and response to treatment [7,8,9]. CTCs are generally thought to separate from tumors of patients with advanced cancer prior to detection in circulation
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