An exploratory analysis of the IMvigor011 surveillance cohort suggests that patients with high-risk muscle-invasive bladder cancer (MIBC) who maintain a circulating tumor DNA-negative (ctDNA-) status after radical cystectomy demonstrate favorable clinical outcomes, potentially sparing them from adjuvant treatment.
The study, presented at the 2024 Society of Urologic Oncology (SUO) annual meeting, examined disease-free survival (DFS) and overall survival (OS) in patients with high-risk MIBC who had persistent ctDNA-negative biomarker status post-cystectomy. The IMvigor011 trial is a global, double-blind, randomized Phase III study evaluating atezolizumab versus placebo in patients with high-risk MIBC who are ctDNA positive post-cystectomy.
The surveillance cohort analysis focused on patients who maintained ctDNA-negative status for 12 months post-cystectomy. Out of 286 patients identified with ctDNA-negative status, 171 met the inclusion criteria for the surveillance analysis, and 144 completed ctDNA surveillance and continued with radiographic evaluation.
The median age of the overall ctDNA-negative sub-cohort was 69 years, with the majority being male (78.9%) and White (56.1%). ECOG performance status was 0 in 67.3% of cases. Within the surveillance cohort, 8.8% experienced disease recurrence, with 11 patients having distant recurrence and 4 having local recurrence.
The 12- and 18-month DFS rates were 92% and 88%, respectively, in the ctDNA-negative surveillance cohort. In an exploratory analysis of DFS outcomes according to PD-L1 subgroups (IC0/1 vs. IC2/3), the median DFS was not reached in either subgroup, and DFS outcomes were similar regardless of PD-L1 status.
The overall survival (OS) analysis is still immature, but the 12- and 18-month OS rates were 100% and 98%, respectively, with a median follow-up of 16.3 months and only a few OS events registered.
According to Dr. Joaquim Bellmunt, Associate Professor at Harvard Medical School and Director of Bladder Cancer Center at Genitourinary Oncology Program of Dana-Farber Cancer Institute, serial ctDNA testing may have greater clinical utility than landmark ctDNA testing as a risk stratification tool for patients with high-risk MIBC. He also noted that within the ctDNA-negative sub-cohort, ctDNA status aids in selecting patients for surveillance with a favorable clinical prognosis regardless of PD-L1 status, increasing confidence that patients with persistent ctDNA-negative status post-cystectomy may be spared adjuvant treatment.
