Adjuvant cisplatin-based combination chemotherapy for lymph node (LN)-positive urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC): a retrospective international study of more than 1500 patients

OBJECTIVE: To compare outcomes of patients with lymph node-positive urothelial carcinoma of the bladder (UCB) treated with or without adjuvant cisplatin-based combination chemotherapy (AC) after radical cystectomy (RC).

PATIENTS AND METHODS: We retrospectively analyzed 1,523 patients with lymph node-positive UCB, who underwent RC with bilateral pelvic lymph node dissection. All patients had no evidence of disease after RC. AC was administered within 3 months. Competing-risks models were applied to compare UCB-related mortality.

RESULTS: Of the 1523 patients, 874 (57.4%) received AC. The cumulative 1-, 2- and 5-year UCB-related mortality rates for all patients were 16%, 36% and 56%, respectively. Administration of AC was associated with an 18% relative reduction in the risk of UCB-related death (SHR 0.82, p=0.005). The absolute reduction in mortality was 3.5% at 5 years. The positive effect of AC was detectable in patients ≤70 years, in women, in pT3-4 disease, and in those with a higher lymph node density and lymphovascular invasion. This study is limited by its retrospective and non-randomized design, selection bias, the absence of central pathologic review and lack in standardization of lymph node dissection and cisplatin-based protocols.

CONCLUSION: AC seems to reduce UCB-related mortality in patients with lymph node-positive UBC after RC. Younger patients, women and those with high-risk features such as pT3-4 disease, a higher lymph node density and lymphovascular invasion appear to benefit most. Appropriately powered prospective randomized trials are necessary to confirm these findings.