CTCs could be a potential biomarker for treatment resistance with docetaxel

Measurement of circulating tumour cells (CTCs) could be used as a biomarker to predict the treatment to docetaxel in men with advanced prostate cancer.

This was the finding of a study by a team from Barts Cancer Institute, London, UK. Docetaxel is recommended as a treatment option for men with hormone-resistant metastatic prostate cancer (mHSPC) as it improves overall survival (OS) and time to disease progression.¹ The drug is also effective in metastatic castration-resistant prostate cancer (mCRPC).² 

However, not all patients respond to chemotherapy with docetaxel and some become treatment-resistant. The team from Barts wondered if it was possible to somehow identify those patients who would become treatment resistant. They turned their attention to CTCs, which are a subset of cells in the blood which serve as a metastatic seed for cancer as it spreads. The researchers collected blood samples from patients with both mHSPC and mCRPC and used the Parsortix system to separate the CTCs from the blood sample.³ 

Findings

A total of 56 men with advanced prostate cancer were included and at total of 205 samples were obtained from 44 mHSPC and 12 mCRPC patients. The presence of CTCs were detected in 61% of samples and 75% of patients with progressive disease (PD) had a positive score prior to docetaxel chemotherapy. 

Analysis of pre-chemotherapy CTCs revealed a significant inverse correlation of CTC parameters with OS and progression-free survival (PFS). A CTC positive score and, in particular, the presence of several subtypes of CTC (e.g., cytokeratin, CK) had the most significant correlation with overall survival. For instance, in mCRPC patients, the correlation of CTC score with OS was -0.85 (p = 0.0095), as was a high total CTC number and OS (-0.69, p = 0.031). In addition, the number of CK+CTCs were significantly correlated with OS in both mHSPC and mCRPC (-0.46, p = 0.0013). 

Using Kaplan-Meier analysis of CTCs before chemotherapy showed that both a positive CTC score and the presence of greater than 1 CK + CTC, significantly predicted poor OS in both prostate types (p = 0.011) and OS (p = 0.0018) and progression-free survival (p = 0.024) in mCRPC alone. In contrast, with greater than 5 CTC was the best predictor of poor OS (p = 0.019) in mHSPC. 

In conclusion, the researchers wrote that ‘These findings provide a promising potential solution to predicting and monitoring DOC resistance using a non-invasive and easily repeatable system.’

References

1. NICE Evidence summary (ESUOM50). Hormone-sensitive metastatic prostate cancer: docetaxel 2016. www.nice.org.uk/advice/esuom50/chapter/Key-points-from-the-evidence#summary (accessed November 2021).
2. Schallier D et al. Docetaxel in the treatment of metastatic castration-resistant prostate cancer (mCRPC): an observational study in a single institution. Anticancer Res 2012;32(2):633–41.
3. Davies C. Circulating tumour cell analysis to evaluate docetaxel treatment response and resistance markers in prostate cancer. NCRI abstract. https://abstracts.ncri.org.uk/abstract/circulating-tumour-cell-analysis-to-evaluate-docetaxel-treatment-response-and-resistance-markers-in-prostate-cancer/