ctDNA-guided or ctDNA-stratified adjuvant immunotherapy compared with observation or placebo after radical surgery for muscle-invasive urothelial carcinoma: a GRADE-assessed systematic review and meta-analysis
In brief
ctDNA-guided adjuvant immunotherapy cuts recurrence risk by half after bladder cancer surgery
In a meta-analysis of three randomized trials, patients whose postoperative ctDNA was used to select adjuvant checkpoint inhibition experienced about a 54% lower risk of disease recurrence and a 44% lower risk of death, without a clear rise in serious side effects. The data are promising but still too limited to make ctDNA testing a universal standard, so assay validation and shared decision-making remain essential.
- Journal
- World journal of urology (Q1)
- Published
- 27 August 2026
- Study design
- Systematic review of cohort studies
- Evidence level
- Level 2, Moderate (CEBM 2a)
- Authors
- Wajahat Mirza, Khalid Hussain, Adeel Anwaar, Abdullah Shaikh, Muhammad Faizan Sajid, Wajiha Irfan, et al.
- PMID
- 42661024
- DOI
- 10.1007/s00345-026-06742-1
Why clinicians should know about it
- Picked for Urology (paper of the day, 30 August 2026): ctDNA‑guided adjuvant immunotherapy meta‑analysis for muscle‑invasive urothelial carcinoma
Abstract
BACKGROUND: Adjuvant immunotherapy after radical surgery for muscle-invasive urothelial carcinoma has produced heterogeneous trial-level results, partly because clinicopathological risk factors do not completely identify patients with molecular residual disease (MRD). Circulating tumor DNA may refine postoperative treatment selection by distinguishing patients who are most likely to benefit from immune checkpoint inhibition from those who may experience unnecessary toxicity. METHODS: This systematic review and meta-analysis was conducted according to the for Systematic Reviews and Preferred Reporting Items Meta-Analyses 2020 guidelines. PubMed/MEDLINE, Embase, and Scopus were searched from their inception until May 2026. Prospective comparative studies evaluating ctDNA-guided or ctDNA-stratified adjuvant immunotherapy versus observation or placebo after radical surgery for muscle-invasive urothelial carcinoma were included. Hazard ratios were pooled for time-to-event outcomes using generic inverse variance models, and risk ratios were pooled for dichotomous safety outcomes using Mantel-Haenszel random-effects models. The risk of bias was assessed using ROB2, and the certainty of evidence was evaluated using GRADE. RESULTS: Five reports representing three independent randomized trial datasets were included. The ctDNA-defined efficacy population included 310 patients receiving adjuvant immunotherapy and 208 receiving observation or placebo, whereas the pooled safety analysis included 632 and 529 patients, respectively. ctDNA-guided or ctDNA-stratified adjuvant immunotherapy significantly improved disease-free survival (HR 0.46, 95% CI 0.32-0.66; P < 0.0001; I²=38%) and overall survival (HR 0.56, 95% CI 0.44-0.72; P < 0.00001; I²=0%). Any-grade adverse events were not significantly increased (RR 1.05, 95% CI 0.98-1.12), nor were grade ≥ 3/3-4 adverse events (RR 1.44, 95% CI 0.98-2.11) or serious adverse events (RR 1.25, 95% CI 0.87-1.80). CONCLUSIONS: ctDNA-guided or ctDNA-stratified adjuvant immunotherapy after radical surgery was associated with improved disease-free and overall survival without a statistically significant pooled increase in major toxicities. ctDNA is a promising tool for residual molecular disease that may inform postoperative immunotherapy selection; however, current evidence remains insufficient to establish ctDNA-guided selection as a definitive standard of care. Implementation should remain linked to validated assay platforms, patient fitness assessment, and individualized shared decision-making. CLINICAL TRIAL REGISTRATION: Not applicable. This study was not a clinical trial.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.