Status:
Completed
Clinicaltrials.gov identifier:
Sponsor:
EORTC with collaboration from GETUG, NCRI, NCIC and AUO
Primary Investigator(s):
Cora N. Sternberg, MD
Accrual:
284
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)
Rationale:
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
Comments:
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.
Results:
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.
