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

The therapeutic paradigm of metastatic urothelial carcinoma (UC) is rapidly shifting and new biomarkers are needed to enhance patient selection. Early identification of dynamic predictors of outcome may be a key to optimize the sequence of effective therapies in metastatic UC patients. Blood samples from patients receiving first-line MVAC chemotherapy were collected at baseline (T) and after 2 cycles (T). Samples were processed by immunomagnetic beads (AdnaTest ProstateCancerSelect kit) and the expression of , and 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 (≥0.40 ng/μl), (≥0.10 ng/μl) and (≥0.20 ng/μl). CTC variation (T/T) was split in favorable (+/-, -/-, -/+) and unfavorable groups (+/+). Cox regression analyses evaluated associations with clinical factors. In this pilot study to assess a new CTC detection method, among 31 evaluable patients, 17 (54.8%) were CTC-positive at T. 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%,  = 0.006) and OS (20% vs. 63.5%,  = 0.017). Significance was maintained after controlling for liver metastases ( = 0.031 and  = 0.025 for PFS and OS) and MSKCC score ( = 0.014 and 0.025). 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.