Clinical Significance of Early Changes in Circulating Tumor Cells from Patients Receiving First-Line Cisplatin-Based Chemotherapy for Metastatic Urothelial Carcinoma.

ABSTRACT: Background: The therapeutic paradigm of metastatic urothelial carcinoma (UC) is rapidly shifting and new biomarkers are needed to enhance patient selection. Objective: Early identification of dynamic predictors of outcome may be a key to optimize the sequence of effective therapies in metastatic UC patients. Methods: Blood samples from patients receiving first-line MVAC chemotherapy were collected at baseline (T₀) and after 2 cycles (T₂). Samples were processed by immunomagnetic beads (AdnaTest ProstateCancerSelect kit) and the expression of EPCAM, MUC1 and ERBB2 was studied using multiplex-PCR. Circulating tumor cell (CTC) positivity and cutoffs, obtained by receiver operator characteristic (ROC) curve analysis in healthy donors, were: ?1 positive marker among EPCAM (?0.40?ng/?l), MUC1 (?0.10?ng/?l) and ERBB2 (?0.20?ng/?l). CTC variation (T₀/T₂) was split in favorable (+/-, -/-, -/+) and unfavorable groups (+/+). Cox regression analyses evaluated associations with clinical factors. Results: In this pilot study to assess a new CTC detection method, among 31 evaluable patients, 17 (54.8%) were CTC-positive at T₀. No association was found between CTC and objective response to MVAC. CTC dynamic changes better predicted 3-year progression-free (PFS) and overall survival (OS) compared to CTC status assessed at single time points. Unfavorable trend was univariably detrimental on 3-year PFS (10% vs. 49.2%, p?=?0.006) and OS (20% vs. 63.5%, p?=?0.017). Significance was maintained after controlling for liver metastases (p?=?0.031 and p?=?0.025 for PFS and OS) and MSKCC score (p?=?0.014 and 0.025). Conclusions: Newly described early CTC changes during chemotherapy might be useful to improve our prognostic ability. Pending validation, these results could fulfill the promise to help accelerating therapeutic sequences.

SUBMITTER: Fina E 

PROVIDER: S-EPMC5181661 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature