Preoperatief ctDNA voorspelt upstaging en recidief bij hoogrisico niet-spierinvasieve blaaskanker

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.