Patients with muscle-invasive bladder cancer have varied outcomes after cystectomy. Circulating tumor DNA (ctDNA)–based detection of molecular residual disease may identify patients high risk for recurrence after cystectomy who can benefit from adjuvant immunotherapy, thus sparing patients lower risk from unnecessary treatment burden.
In a phase 3, double-blind, randomized trial, we used serial ctDNA testing to monitor (for up to 1 year) patients with muscle-invasive bladder cancer and no radiographic evidence of disease after surgery. Eligible patients who tested ctDNA-positive during surveillance were randomly assigned in a 2:1 ratio to receive intravenous atezolizumab or placebo every 4 weeks for up to 1 year. The primary end point was investigator-assessed disease-free survival. Overall survival was a secondary end point that was assessed in a hierarchical fashion to control for alpha. Patients who persistently tested ctDNA-negative did not receive atezolizumab or placebo. Research Summary ctDNA-Guided Adjuvant Atezolizumab in Muscle-Invasive Bladder Cancer
A total of 761 patients were enrolled; 250 eligible patients who tested ctDNA-positive underwent randomization (167 to the atezolizumab group and 83 to the placebo group). The median disease-free survival was 9.9 months with atezolizumab, as compared with 4.8 months with placebo (hazard ratio for first event of disease recurrence or death, 0.64; 95% confidence interval [CI], 0.47 to 0.87; P=0.005). The median overall survival was 32.8 months with atezolizumab, as compared with 21.1 months with placebo (hazard ratio for death, 0.59; 95% CI, 0.39 to 0.90; P=0.01). A total of 28% of the patients who received atezolizumab and 22% of those who received placebo had adverse events of grade 3 or 4 (related to atezolizumab or placebo in 7% vs. 4%); 3% and 2% of the patients, respectively, had fatal adverse events (related to atezolizumab or placebo in 2% vs. none). Among 357 patients with persistent ctDNA-negative status, disease-free survival was 95% the end of the 1-year monitoring period and 88% 2 years.
Among patients with muscle-invasive bladder cancer, ctDNA-guided adjuvant therapy with atezolizumab led to significantly longer disease-free survival and overall survival than placebo. (Funded by F. Hoffmann–La Roche; IMvigor011 ClinicalTrials.gov number, NCT04660344.)
Trimodality therapy is an effective potential alternative to radical cystectomy for recurrent high-grade T1 urothelial cancer of the bladder.
Perioperative durvalumab showed an improvement of 2-year OS of 82.2 vs 75.2%, 2-year PFS was improved 67.8 vs 59.8%. There was interestingly no difference in the rates of grade 3-4 toxicity in the SOC vs periop-IO group. This is likely going to become the SOC in resectable bladder cancer.
Many had neoadjuvant therapy, still no difference between standard or extended lymphadenectomy for muscle-invasive bladder cancer. So, it seems more is not better.
The poor OS of 1.5 years in node-positive patients is striking in this retrospective review of 287 patients treated with definitive intent. The OS was not different between those treated with TURBT + chemoradiation vs. chemotherapy + radical cystectomy, suggesting that surgery may not be superior to multi-modal therapy and QOL may be superior in a non-operative approach.
Retrospective review showing equivocal outcomes in cT2-T4N0 patients treated with radical cystectomy vs TURBT + chemoradiation. There were similar rates of neoadjuvant chemotherapy being given in both groups. Based on prospective data, the SOC remains cisplatin-based neoadjuvant chemo followed by radical cystectomy; however, trimodality therapy may not have worse outcomes, and it would be great to see a prospective head-to-head study.