Presentation Authors: Gian Maria Busetto*, Francesco Del Giudice, Cristina Raimondi, Paola Gazzaniga, Ettore De Berardinis, Roma, Italy
Introduction: Non-muscle invasive bladder cancer current scoring models cannot precisely predict the individual disease course and do not reflect the optimal treatment. Furthermore, in the era of precision medicine, it is unconceivable that risk stratification might disregard molecular features of cancer, and the imprecision of these risk tools based on combined pathological and clinical features highlight the requirement of molecular biomarkers able to personalize treatments. Circulating tumor cells (CTCs) are regarded as surrogates for early metastatic spread of disease. In addition, the molecular characterization of CTCs may represent a tool to investigate the basic mechanism of cancer biology since CTCs have the potential to give information regarding the intratumour heterogeneity and evolution.
Methods: We conducted a prospective observational study in 102 patients with a pathologically confirmed high-risk T1G3 transitional cell tumor, treated at our Institution between 2010 and 2013 according to standard international guidelines (TURB followed by re-TURB and maintenance BCG). CTCs were isolated before the first TURB through CellSearch system. We had previously demonstrated that the presence of CTC is significantly associated with shorter TFR and TTP in a median follow up of 24 months. Updated outcome analysis and mature CSS and OS results are reported here in a median follow up of 63 months.
Results: CTCs were found in 20/102 (20%) patients. Median CTCs number was 1 (range: 1-50). Patients that were still alive at the end of the study were followed for at least 61 months. The final analysis substantiated results obtained at 24 months of median follow-up showing a statistically significant p value for time to first recurrence, second recurrence and time to progression. The presence of at least 1 CTC was here found to be clearly associated also with shorter metastasis free survival, cancer-specific survival and overall survival . Multivariable analysis confirmed that CTCs, as compared to the standard predictive variables (multifocality, CIS, lymph vascular invasion) have the strongest negative prognostic impact for all the outcomes analyzed.
Conclusions: These results suggest that some patients with T1G3 NMIBC might have a clinically undetected systemic disease connoting CTCs as an useful tool to improve the currently used risk stratification algorithms. In conclusion, a closer follow-up, an early radical surgery or even a systemic treatment might be recommended in CTC positive NMIBC patients.