760P Platinum-based adjuvant chemotherapy in upper tract urothelial carcinomas (UTUCs): A change of paradigm? A meta-analysis of aggregate data

Abstract

Upper tract urothelial carcinomas (UTUCs) are a rare subset of urothelial carcinomas arising from urothelial cells of the ureter up to the renal calyceal system. Radical nephroureterectomy (RNU) is the gold standard treatment for UTUC patients, but this surgery leads to high risk of relapse and death from cancer. The present meta-analysis aims to evaluate the role of platinum-based adjuvant chemotherapy (AC) for patients with locally advanced UTUCs (staged as either pT2–T4 N0–N3 M0 or pTany N1–3) after RNU. Eligible studies were identified using Pubmed/Medline, Cochrane library, Embase and meeting abstracts. Searches were last updated on March 30, 2020. Eligible studies reported survival and/or disease-free survival (DFS) outcomes expressed as hazard ratio (HR) and 95% confidence intervals (CIs) for patients treated with platinum-based AC compared to observation alone. Primary outcomes of interest were overall survival (OS), cancer-specific survival (CSS) and DFS. A total of 16 studies were eligible for analysis: 15 retrospective studies and 1 phase 3 randomized control trial (RCT). In total, data from 6275 patients were reported with median number of patients included in each cohort of 65 (range: 11–2491 patients) and a median follow-up of 37,5 months (range 17,8-53,9 months). In patients receiving platinum-based AC, rates of weighted median 5-years OS, CSS and PFS were 72,3%, 75% and 63,3%, respectively, and appeared to be superior compared to control. Platinum-based AC resulted in a 51% risk reduction disease relapse (pooled HR 0.49; 95% CI: 0.36–0.66), while the benefit in OS (pooled HR 0.80; 95% CI: 0.51–1.26) and CSS (pooled HR 0.87; 95% CI: 0.65–1.17) was not statistically significant compared to observation after RNU. Conversely, platinum-based AC showed a modest OS benefit with a pooled HR 0.75 (95% CI: 0.57–0.99) in a posthoc analysis combing multivariable HRs with estimated HRs from Kaplan-Meier curves. With available evidence from published data, we suggest that platinum-based AC is associated with improved DFS and a modest OS benefit after RNU in patients with locally advanced UTUCs. Further prospective randomized studies are needed to confirm our findings.