Randomized Phase III Trial Comparing Immediate Versus Deferred Chemotherapy After Radical Cystectomy in Patients With pT3-pT4, and/or N+M0 Transitional Cell Carcinoma (TCC) of the Bladder

EORTC with collaboration from GETUG, NCRI, NCIC and AUO
Primary Investigator(s): 
Cora N. Sternberg, MD
Study Design: 
Patients at least 90 days out of cystectomy with pT3-T4 and/or node positive urothelial cancer of the bladder were randomized to either immediate chemotherapy or deferred chemotherapy (latter being given at clinical relapse of disease)
Adjuvant chemotherapy has been evaluated in small single center studies and the trials have never been powered adequately to demonstrate a benefit with adjuvant chemotherapy. This large, multi-center trial was designed through the EORTC to try to evaluate adjuvant chemotherapy more rigorously
Unfortunately, the trial was closed early due to difficulties with accrual. One can only speculate that the trend in OS may have become significant if more patients had been enrolled. A meta analysis of the literature suggests a benefit of adjuvant chemotherapy but is limited by severe between trial heterogeneity. An updated individual patient data meta-analysis and biomarker research are needed to further elucidate the potential for survival in subgroups of patients. Although immediate chemotherapy after radical cystectomy led to a significant improvement in PFS, overall survival was not improved. However, immediate chemotherapy might extend survival in patients without lymph-node involvement.
This is the largest randomized trial ever reported of adjuvant chemotherapy in patients with muscle invasive bladder cancer. Immediate adjuvant cisplatin based combination chemotherapy after radical cystectomy led to a statistically significant improvement in PFS. 5 yr PFS was 47.6% vs 31.8% on the deferred arm. The median PFS was 3.11 years vs 0.99 years on the deferred arm (HR =0.54 p = 0.54 (95% CI : 0.40 – 0.73) P < 0.0001). A non-significant reduction of 22.2% in the risk of death was also observed.