Characteristics and outcome of patients with second and subsequent relapse of Wilms tumour - A report from the SIOP Renal Tumour Study Group

Background: Second or subsequent relapses of Wilms tumour (WT) are rarely reported. We assessed the characteristics, treatments, and outcome of such patients through a retrospective international cohort study of patients treated according to recent SIOP-RTSG protocols. Methods: Patients with a second or subsequent relapse enrolled in SIOP WT 2001 and the UK-IMPORT study, and registered in the SIOP-RTSG database between 2001 and 2021 were included. Risk groups were defined per the SIOP-RTSG-2016 UMBRELLA protocol (AA-BB (second relapse after initial standard risk (AA) relapse), BB-CC (initial high risk (BB) relapse), and CC-CC (initial very high risk (CC) relapse). Five-year event-free survival (EFS) and overall survival (OS) rates were estimated using Kaplan-Meier and competing risk methods; survival between relapse risk groups was compared with log-rank testing. Findings: Among 572 patients with first relapse, 114 (20%) patients experienced a subsequent relapse. The estimated 5-year EFS and OS after second relapse were 17.7% (95% Confidence Interval (CI): 11.1–28.0%) and 22.4% (95% CI: 15.3–32.9%). In group AA-BB (n = 39) 5-year EFS and OS were 39.0% (95% CI: 25.0–60.7%) and 41.0% (95% CI: 26.8–62.8%). In group BB-CC (n = 32), 5-year EFS was 14.8% (95% CI: 6.05–36.3%) and 5-year OS was 21.9% (95% CI: 10.9–44.0%). All CC-CC patients (n = 35) either died within 3 years of the second relapse or lacked adequate follow-up. Group AA-BB had predominantly been treated with ICE/CyCE regimens, and group BB-CC patients mainly with VIT/TOTEM regimens. Conclusion: A second relapse WT remains curable in a proportion of AA-BB patients. In contrast, survival rates for BB-CC patients are minimal and dismal for CC-CC patients, who should be allocated to a relevant early-phase trial if feasible.