Outcome of patients with a first relapse after intermediate- or high-risk Wilms tumor, treated according to SIOP WT 2001/UK-IMPORT study; A report from the SIOP renal tumor study group

Background: Patients with a Wilms tumor (WT) who relapse following initial therapy with more than only vincristine and actinomycin-D are considered high-risk (group BB) or very high-risk (group CC) relapse by the International Society of Pediatric Oncology – Renal Tumor Study Group (SIOP-RTSG). We aimed to retrospectively analyze the characteristics and outcome of BB and CC patients. Methods: We included all patients with first relapsed WT that would currently be considered BB (n = 148) and CC (n = 72) relapse and registered in the SIOP 2001/UK-IMPORT study. We collected information on relapse treatment and calculated 5-year event-free (EFS) and overall survival (OS) rates per relapse risk group and treatment. Multivariable Cox regression analysis was performed to identify patient and tumor characteristics that were significantly associated with survival. Findings: The 5-year estimated EFS and OS rates of BB patients were 62·7% (95% CI: 54·9–71·6%) and 67·6% (95% CI: 59·8–76·4%), respectively. Five-year survival rates for the subset of BB patients treated with VAD and RT (n = 42/94) were 58·7% (95% CI: 45·0–76·6%) for EFS and 66·5% (95% CI: 53·1–83·2%) for OS. Five-year estimated EFS and rates for CC patients were 17·4% (95% CI: 10·4–29·0%) and 18·6% (95% CI: 11·3–30·5%), respectively. In multivariable Cox regression analysis, patients seemed to benefit from high dose chemotherapy and autologous stem cell rescue (HDCT) and surgery at first relapse. Interpretation: Second-line treatment was able to rescue two-thirds of BB relapse patients. In contrast, survival rates in CC patients at first relapse remain poor with conventional drugs, even with camptothecin-containing regimens. A subset of BB and CC patients may benefit from HDCT and surgery at relapse. However, to validate these findings, they must be reevaluated in future trials to eliminate bias from the analyses that is inherent to retrospective studies.