Clinical application of circulating tumor cells in patients with metastatic castration-resistant prostate cancer

Resumo

Background. Prostate cancer (PCa) is the most common diagnosed male malignancy in the Western world. One third of patients will develop metastatic castration resistant prostate cancer (mCRPC). To monitor systemic disease, the study of circulating tumor cells (CTCs) can be a supplement or an alternative to the serum PSA and imaging methods. In the present study we assessed the value of CTC count and molecular characterization to manage mCRPC patients. Methods. Blood samples from 29 mCRPC patients treated with first line taxanes were analyzed at four different time points. Samples were first processed by the Cellsearch platform. Besides we did a CTC isolation and a gene expresson analysis by RT-qPCR at baseline in 29 mCPRC. In addition a whole gene expression analysis was carried out on blood samples extracted from 9 patients and from 6 healthy donors. Results. CTC count worked as a prognostic factor: median OS was 16 months for those patients with ≥5 CTCs at baseline versus not reached for those < 5 CTCs. In addition to the CTC count we identified a molecular CTCs-signature that could be useful for the initial diagnosis, prognosis and therapy monitoring. Thus, high levels of AR, CYP19 and GDF15 were associated with poor PFS rates while AR, GDF15 and BIRC5 were also found as consistent predictors of OS in the univariate analysis. Finally after the global gene expression approach we found a general stress-survival phenotype in the CTC population of mCRPC patients partially based on cell proliferation, apoptosis, adhesion and migration. Conclusions. In our cohort CTC count using CellSearch technology has prognostic value. In parallel, we have also demonstrated the feasibility of an alternative method of CTC isolation and gene expression analysis, identifying a panel of genes with prognostic relationship and deserves to be explored for the treatment monitoring.