Preoperative Circulating Tumor DNA Predicts Upstaging and Recurrence in High-Risk Nonmuscle-Invasive Bladder Cancer...

Area of Science:

• Urology
• Oncology
• Molecular Diagnostics

Background:

• High-risk non-muscle invasive bladder cancer (NMIBC) poses a significant challenge due to potential progression.
• Radical cystectomy (RC) is a treatment option, but predicting outcomes remains crucial.
• Circulating tumor DNA (ctDNA) analysis is emerging as a non-invasive tool for cancer monitoring.

Purpose of the Study:

• To evaluate if pre-cystectomy ctDNA status predicts recurrence-free survival (RFS) in high-risk NMIBC patients.
• To determine the correlation between pre-cystectomy ctDNA and pathological upstaging after radical cystectomy (RC).
• To assess the utility of ctDNA in identifying patients with locally advanced disease or lymph node metastasis.

Main Methods:

• A bi-center prospective analysis of 56 high-risk NMIBC patients (N0M0) undergoing RC (2021-2023).
• Serial tumor-informed ctDNA analyses were performed pre- and post-RC, with molecular residual disease (MRD) assessed within 90 days.
• Recurrence-free survival (RFS) was analyzed using the Kaplan-Meier method, with comparisons based on pre-RC ctDNA detectability.

Main Results:

• Of 45 patients with pre-RC ctDNA data, 33.3% had detectable ctDNA.
• Detectable pre-RC ctDNA was significantly associated with pathological upstaging (≥pT2) and lymph node positivity (pN+) (OR=13.0, p<0.001).
• Detectable pre-RC ctDNA correlated with significantly worse RFS (log-rank, p<0.0001, HR=11) and detectable MRD ctDNA also predicted worse RFS (log-rank, p<0.0001, HR=14.1).

Conclusions:

• Pre-cystectomy detectable ctDNA is a strong predictor of worse recurrence-free survival in high-risk NMIBC patients.
• ctDNA status before radical cystectomy correlates with increased risk of pathological upstaging and lymph node metastasis.
• Tumor-informed ctDNA analysis holds promise as a prognostic biomarker in NMIBC management.