Epidermal Growth Factor Receptor Status in Circulating Tumor Cells as a Predictive Biomarker of Sensitivity in Castration-Resistant Prostate Cancer Patients Treated with Docetaxel Chemotherapy

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.

Circulating Tumor Cells as a Marker for Progression‐free Survival in Metastatic Castration‐naïve Prostate Cancer

“…Together, this suggests that the detection limit due to CTC load is not the only reason for the association between EGFR‐positivity and poor prognosis in the present study. In support of our findings, a recent study reports that EGFR expressing CTCs are associated with poor response to docetaxel in CRPC patients . Further, the association of EGFR expression with a poor prognosis is in accord with previous findings indicating that pEGFR is an independent prognostic marker for cancer‐specific survival in PC .…”

The role of biomarkers in the management of bone-homing malignancies

“…Further CTC features, besides their number, have been investigated for prognostic purposes. Indeed, Okegawa et al have recently described that the expression of epidermal growth factor receptor, in CTC isolated from castration-resistant PC patients treated with docetaxel, correlates with shorter overall survival (5.5 vs 20.0 months), as compared to its absence (p < .001) [87] .…”

ROR1 is highly expressed in circulating tumor cells and promotes invasion of pancreatic cancer

“…Circulating tumor cells (CTCs) are tumor cells that induce metastasis, which is responsible for the majority of cases of cancer-associated mortality (7). CTCs have been widely recognized as tumor-or metastasis-derived cells, which move into the circulatory system from the primary tumor site during surgical resection and lead to disease recurrence in patients with cancer (8)(9)(10)(11). CTCs have already been widely used as a biomarker for the assessment of cancer prognosis and response to therapy (12).…”