Preoperative ctDNA Predicts Upstaging and Recurrence in High-Risk Non-Muscle Invasive Bladder Cancer Undergoing Radical Cystectomy
Menée sur 56 patients atteints d'un cancer non invasif de la vessie présentant un risque élevé de récidive et traité par cystectomie radicale entre 2021 et 2023 (durée médiane de suivi : 14 mois ; âge médian : 67 ans), cette étude met en évidence une association entre la détection de l'ADN tumoral circulant avant l'opération et la survie sans récidive ainsi que le risque de classification de la maladie à un stade plus élevé
Objectives : To assess if pre-cystectomy ctDNA status predicts recurrence-free survival (RFS) and correlates with disease upstaging in high-risk non-muscle invasive bladder cancer (NMIBC) patients undergoing radical cystectomy (RC).
Methods : A bi-center analysis of patients with high-risk NMIBC (N0M0) who underwent RC between 2021-2023 and had prospective serial tumor-informed ctDNA analyses performed before and after RC. The molecular residual disease (MRD) window was defined as the initial 90 days after RC. The primary endpoint -RFS was analyzed with the Kaplan-Meier method.
Results : Fifty-six NMIBC patients with a median follow-up time of 14 months (IQR 6-18) and a median age of 67 years (IQR 62-72) were included; among them, 45 patients had pre-RC ctDNA status available, 15 (33.3%) had detectable and 30 (66.7%) had undetectable ctDNA. Twelve patients had BCG unresponsive disease (26.8%). The most common pre-RC pathology was T1HG (60%) and T1HG+CIS (28.9%). Detectable pre-RC ctDNA were more commonly upstaged (
≥
pT2) 66.7% vs. 13.3% and 33.3% vs. 0% had pN+ (odds ratio=13.0 [3.13-66.1], p<0.001). Among patients with undetectable ctDNA, 20% had pT0 and none had
≥
pT3 or pN+ disease. On survival analysis, detectable pre-RC ctDNA had worse RFS than undetectable ctDNA (log-rank, p<0.0001, hazard ratio [HR]=11 [2.27-53.8]), with worse 6-month RFS of 64.3% [43.5-95] vs. 100% and 12-month RFS of 38.6% [17.1-87.2] vs. 95.7% [87.7-100], respectively. Detectable MRD ctDNA was associated with worse RFS than undetectable ctDNA (log-rank, p<0.0001, HR=14.1 [3.12-63.7], p=0.001).
Conclusions : Detectable ctDNA status for high-risk NMIBC pre-RC was associated with worse RFS, increased risk of pathological upstaging, and locally advanced disease with lymph node metastasis.
Journal of Urology , résumé, 2026