Top Line: Is molecular residual disease ready to guide management following cystectomy?
The Study: Liquid biopsy–based ctDNA testing has emerged as a powerful prognostic tool in muscle-invasive bladder cancer, with ctDNA positivity after cystectomy identifying patients at high risk for recurrence. The phase 3 IMvigor011 trial used post-cystectomy serial ctDNA surveillance to risk-stratify adjuvant treatment. Of 761 enrolled patients, 250 who became ctDNA-positive (despite no radiographic disease) were randomized 2:1 to atezolizumab versus placebo for up to 1 year; persistently ctDNA-negative patients were observed. Among ctDNA-positive patients, the addition of early atezolizumab doubled median disease-free survival from 5 to 10 months (HR 0.64) and significantly improved overall survival from 2 to 33 months (HR 0.59). Toxicity was consistent with prior atezo experience. Meanwhile, patients who remained ctDNA-negative did remarkably well without any adjuvant therapy with 95% alive without disease at 1 year and 88% at 2 years.
TBL: These data support ctDNA-guided adjuvant immunotherapy, shifting treatment decisions from pathologic risk alone to biologically-informed. | Powles, N Engl J Med 2025
The Study: Liquid biopsy–based ctDNA testing has emerged as a powerful prognostic tool in muscle-invasive bladder cancer, with ctDNA positivity after cystectomy identifying patients at high risk for recurrence. The phase 3 IMvigor011 trial used post-cystectomy serial ctDNA surveillance to risk-stratify adjuvant treatment. Of 761 enrolled patients, 250 who became ctDNA-positive (despite no radiographic disease) were randomized 2:1 to atezolizumab versus placebo for up to 1 year; persistently ctDNA-negative patients were observed. Among ctDNA-positive patients, the addition of early atezolizumab doubled median disease-free survival from 5 to 10 months (HR 0.64) and significantly improved overall survival from 2 to 33 months (HR 0.59). Toxicity was consistent with prior atezo experience. Meanwhile, patients who remained ctDNA-negative did remarkably well without any adjuvant therapy with 95% alive without disease at 1 year and 88% at 2 years.
TBL: These data support ctDNA-guided adjuvant immunotherapy, shifting treatment decisions from pathologic risk alone to biologically-informed. | Powles, N Engl J Med 2025