Tumor-Agnostic Circulating Tumor DNA Testing for Monitoring Muscle-Invasive Bladder Cancer

Abstract

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.

Circulating Tumour DNA and Its Prognostic Role in Management of Muscle Invasive Bladder Cancer: A Narrative Review of the Literature

“…They demonstrated that ctDNA-positive status before cystectomy and 4 and 12 months afterwards was associated with a higher risk of disease progression (HR 6.774, HR 3.673 and HR 30.865, respectively; p < 0.05). Finally, similarly to their previous study, they demonstrated that ctDNA clearance 4 months post-cystectomy was associated with longer progression-free survival, compared to the patients with persistently detectable ctDNA (p = 0.045) [38].…”

Circulating Tumor DNA in Genitourinary Cancers: Detection, Prognostics, and Therapeutic Implications

“…Continuous ctDNA measurements demonstrated an RFS hazard ratio of 78 ( p < 0.001) [ 122 ]. Carrasco et al report that ctDNA-detected mutations in TERT and ATM were predictive of tumor progression before radical cystectomy, at four months post-radical cystectomy, and 12 months post-radical cystectomy (HR 6.774, HR 3.673, and HR 30.865, respectively; p < 0.05) [ 134 ]. Patients with metastatic relapse post-radical cystectomy had significantly higher detectable ctDNA compared to disease-free patients ( p < 0.001), which was detectable at a median of 137 days, compared to clinical diagnosis with cystectomy at 275 days [ 135 ].…”