Prognostic value of circulating tumor DNA in muscle-invasive bladder cancer treated with radical cystectomy: A systematic review and meta-analysis.

e16611 Background: Muscle-invasive bladder cancer (MIBC) is an aggressive disease that carries a high risk of disease recurrence. While traditional prognostic factors have been well established, circulating tumor DNA (ctDNA) has emerged as a biomarker for minimal residual disease (MRTD) in many malignancies, including MIBC.Various trials have evaluated the role of ctDNA in determining post-cystectomy adjuvant therapy, but pooled evaluation of survival outcomes based on ctDNA status remains unknown. Our meta-analysis compare disease-free survival (DFS) and overall survival (OS) based on ctDNA status in MIBC patients. Methods: A systematic literature search was conducted in PubMed, the Cochrane Library, and clinicaltrials.gov through January 2026, and we identified 216 studies evaluating ctDNA in MIBC. Studies reporting DFS and OS according to Signatera-based ctDNA for MRTD after radical cystectomy were evaluated. Hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted and pooled using a random-effects model. Statistical heterogeneity was assessed using I² statistic. The primary endpoints of our analysis were DFS and OS. Results: After screening, 7 studies met our selection criteria. Our pooled analysis had 1434 patients with a median age of 65 (60-69) years and a median follow-up of 53.6 (34-68) months. Patients with a ctDNA positive (ctDNA+ve) had a higher risk of mortality compared to ctDNA-negative (ctDNA-ve) (HR 4.51, 95% CI 2.44–8.33), with substantial heterogeneity (I² = 79.3%). Similarly, ctDNA+ve patients had an increased risk of disease recurrence (HR 8.87,95% CI 4.19–18.78; I² = 87.2%). In ctDNA+ve patients, adjuvant immunotherapy (AI) provided better OS compared to placebo (HR 0.56, 95% CI 0.44-0.72). However, in the ctDNA-ve patients, AI provided limited DFS benefit (HR 0.84, 0.50-1.41). Conclusions: Our meta-analysis demonstrates that patients with ctDNA+ve had inferior DFS and OS compared to those with ctDNA-ve status, irrespective of treatment across diverse study settings. There was no survival benefit with AI in patients with ctDNA-ve status. Post-surgery ctDNA status is a strong prognostic marker and should be incorporated into risk stratification and adjuvant therapy decision-making. Pooled hazards ratios for OS and DFS based on ctDNA. Study HR OS ctDNA+ve HR DFS ctDNA +ve HR DFS within ctDNA-ve HR OS within ctDNA+ve CheckMate 274 2.3 (1.3-4.0) 3.3 (2.1-5.6) 0.99 (0.51-1.93) 0.41 (0.20-0.84) IMVigor010 8.0 (4.9-12.9) 6.3 (4.5-8.9) 1.14 (0.81-1.62) 0.59 (0.42-0.83) NIAGRA 2.4 (1.7-3.3) 11.1 (5.7-20) 0.49 (0.28-0.84) - Nordentoft. 4.0 (1.8-8.8) - - - Lindskrog (NAC) 19.5 (6.9-54.6) 37.7 (8.5-167.1) - - Lindskrog (No NAC) 17.8 (3.9-81.2) 17.8 (3.9-81.2) - - TOMBOLA 2.3 (1.2-4.5) 2.3 (1.2-4.5) - - IMVigor011 - - 0.59 (0.39-0.90) Pooled Results 4.33 (2.58-7.28) 7.11 (3.35-15.07) 0.84 (0.50-1.41) 0.56 (0.44-0.72)