title: 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 ofEPCAM,MUC1andERBB2was 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 amongEPCAM(≥0.40 ng/μl),MUC1(≥0.10 ng/μl) andERBB2(≥0.20 ng/μl). 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 andp= 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.
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Fina
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Necchi
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Giannatempo
authors.affiliation: Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Colecchia
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Raggi
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Daidone
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan, Italy.
authors.forename: Vera
authors.initials: V
authors.lastname: Cappelletti
keywords: Urothelial carcinoma; circulating tumor cells; first-line chemotherapy; prognostic factors