Introduction: Cell-free DNA (cfDNA) has recently emerged as a real-time biomarker for diagnosis, monitoring and predicting therapy response of tumoral disease. Our aim was to evaluate cfDNA as a prognostic biomarker for monitoring muscle-invasive bladder cancer (MIBC) patients after radical cystectomy (RC) at different follow-up time points. Methods: Blood samples from 37 MIBC patients who underwent RC and extended lymphadenectomy in our center were collected at cystectomy and one, four, 12 and 24 months later. cfDNA from plasma samples was quantified and fragmentation patterns were analyzed. Four mutations previously identified in BC tissue from these patients were studied in cfDNA samples by droplet digital PCR to identify presence of circulating tumor DNA (ctDNA) during patients’ follow-up. Results: During a median follow-up of 36 months, 17 (46%) patients progressed and 14 (38%) died due to the BC. The median time to progression and cancer-specific survival (CSS) were 10 and 16 months, respectively. cfDNA level was significantly higher in progressive than non-progressive MIBC patients 12 months after RC (p= 0.045). Of note, cfDNA level and ctDNA status four months after RC were identified as independent prognostic biomarkers of tumor progression (HR 5.290; p= 0.033) and CSS (HR 4.199; p= 0.038), respectively. By contrast, no correlation was found between cfDNA fragmentation and tumor progression nor CSS. ctDNA status detected tumor progression with a median anticipation period of 6 months compared with imaging techniques (p= 0.024). Furthermore, ctDNA clearance four months after RC was significantly associated with patients’ clinical outcomes (p=0.033). Conclusions: cfDNA levels and ctDNA status four months after RC are prognostic biomarkers of tumor progression and CSS in MIBC patients. In addition, cfDNA monitoring is useful to predict patient outcomes after RC. The implementation of cfDNA analysis in the clinical setting could have an impact on disease management since patients could benefit from early treatment. SOURCE OF Funding: This work was supported by the Instituto de Salud Carlos III (ISCIII), project reference number PI17/01343.
