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Circulating tumor DNA (ctDNA) has recently emerged as a real-time prognostic and predictive biomarker for monitoring cancer patients. Here, we aimed to ascertain whether tumor-agnostic ctDNA testing would be a feasible strategy to monitor disease progression and therapeutic response in muscle-invasive bladder cancer (MIBC) patients after radical cystectomy (RC). Forty-two MIBC patients who underwent RC were prospectively included. Blood samples from these patients were collected at different follow-up time points. Two specific mutations ( TERT c.1-124C>T and ATM c.1236-2A>T) were analyzed in the patients' plasma samples by droplet digital PCR to determine their ctDNA status. During a median follow-up of 21 months, 24% of patients progressed in a median of six months. ctDNA status was identified as a prognostic biomarker of tumor progression before RC and 4 and 12 months later (HR 6.774, HR 3.673, and HR 30.865, respectively; p < 0.05). Lastly, dynamic changes in ctDNA status between baseline and four months later were significantly associated with patient outcomes ( p = 0.045). In conclusion, longitudinal ctDNA analysis using a tumor-agnostic approach is a potential tool for monitoring MIBC patients after RC. The implementation of this testing in a clinical setting could improve disease management and patients' outcomes.

Cell-free DNA (cfDNA) has recently emerged as a real-time biomarker for diagnosis, monitoring and prediction of therapy response in tumoral disease. Here, we evaluated cfDNA as a prognostic biomarker for monitoring muscle-invasive bladder cancer (MIBC) patients at different follow-up time points. Blood samples from 37 MIBC patients who underwent radical cystectomy (RC) were collected at cystectomy and 1, 4, 12 and 24 months later. Plasma cfDNA amount and fragmentation patterns were determined. Four mutations were analyzed in cfDNA to detect circulating tumor DNA (ctDNA) during patient follow-up. During a median follow-up of 36 months, 46% of patients progressed; median time to progression was 10 months. cfDNA levels and ctDNA status four months after RC were identified as independent prognostic biomarkers of tumor progression (HR 5.290; p = 0.033) and cancer-specific survival (HR 4.199; p = 0.038), respectively. Furthermore, ctDNA clearance four months after RC was significantly associated with patients' clinical outcomes. In conclusion, cfDNA levels and ctDNA status four months after RC have prognostic implications in MIBC patients. In addition, cfDNA monitoring is useful to predict patient outcomes after RC. cfDNA analysis in the clinical setting could greatly improve MIBC patient management.

Currently, there are no reliable prognostic factors to determine which upper tract urothelial carcinoma (UTUC) patients will progress after radical nephroureterectomy (RNU). We aim to evaluate whether liquid-biopsy-based biomarkers (circulating tumor cells (CTCs), cell-free DNA (cfDNA), and circulating tumor DNA (ctDNA)) were able to predict clinical outcomes in localized UTUC patients undergoing RNU. Twenty patients were prospectively enrolled between 2021 and 2023. Two blood samples were collected before RNU and three months later. CTCs and cfDNA were isolated and evaluated using the IsoFlux system and Quant-iT PicoGreen dsDNA kit, respectively. Droplet digital PCR was performed to determine ctDNA status. Cox regression analysis was performed on CTCs, cfDNA, and ctDNA at two different follow-up time points to examine their influence on tumor progression and cancer-specific survival (CSS). During a median follow-up of 18 months, seven (35%) patients progressed and three (15%) died. Multivariate analysis demonstrated that cfDNA levels three months after RNU are a significant predictor of tumor progression (HR = 1.085; p = 0.006) and CSS (HR = 1.168; p = 0.029). No associations were found between CTC enumeration and ctDNA status with any of the clinical outcomes evaluated. The evaluation of cfDNA levels in clinical practice could improve the disease management of UTUC patients. [ABSTRACT FROM AUTHOR]