Prognostic significance of histopathological response to preoperative chemotherapy in unilateral Wilms' tumor: An analysis of 899 patients treated on the SIOP WT 2001 protocol in the UK-CCLG and GPOH studies.

Gordan M Vujanić,Christian Vokuhl,Rhoikos Furtwängler,Kathy Pritchard‐Jones,Reem Al‐Saadi,Ellen D'Hooghe,Norbert Graf,Tanzina Chowdhury

doi:10.1002/ijc.33707

Abstract

In the SIOP Wilms' tumor (WT) studies, preoperative chemotherapy is used as primary treatment, and tumors are classified thereafter by pathologists. Completely necrotic WTs (CN-WTs) are classified as low-risk tumors. The aim of the study was to evaluate whether a subset of regressive type WTs (RT-WTs) (67%-99% chemotherapy-induced changes [CIC]) showing an exceptionally good response to preoperative chemotherapy had comparably excellent survivals as CN-WTs, and to establish a cut-off point of CIC that could define this subset. The study included 2117 patients with unilateral, nonanaplastic WTs from the UK-CCLG and GPOH-WT studies (2001-2020) treated according to the SIOP-WT-2001 protocol. There were 126 patients with CN-WTs and 773 with RT-WTs, stages I-IV. RT-WTs were subdivided into subtotally necrotic WTs (>95% CIC) (STN-WT96-99) (124 patients) and the remaining of RT-WT (RR-WT67-95) (649 patients). The 5-year event-free survival (EFS) and overall survival (OS) for CN-WTs were 95.3% (±2.1% SE) and 97.3% (±1.5% SE), and for RT-WTs 85.7% (±1.14% SE, P < .01) and 95.2% (±0.01% SE, P=.59), respectively. CN-WT and STN-WT96-99 groups showed significantly better EFS than RR-WT67-95 (P=.003 and P=.02, respectively), which remained significantly superior when adjusted for age, local stage and metastasis at diagnosis, in multivariate analysis, whereas OS were superimposable (97.3 ± 1.5% SE for CN-WT; 97.8 ± 1.5% SE for STN-WT96-99; 94.7 ± 1.0% SE for RR-WT67-95). Patients with STN-WT96-99 share the same excellent EFS and OS as patients with CN-WTs, and although this was achieved by more treatment for patients with STN-WT96-99 than for patients with CN-WT, reduction in postoperative treatment of these patients may be justified.

Highlights

The outcomes for patients with Wilms' tumors (WTs) have significantly improved over the last decades, with >90% overall survival for those with localized, and 80% for those with metastatic nonanaplastic WT.[1,2,3] It is increasingly important to refine the risk groups and find prognostic factors which identify WT subgroups requiring more aggressive treatment, as well as those who need less treatment to reduce the long-term sequelae and improve patients' quality of life
The 5-year event-free survival (EFS) estimates were significantly superior for the completely necrotic Wilms' tumor (CN-WT) (P = .002) and subtotally necrotic (STN)-WT96-99 (P = .02) groups when compared to the rest of regressive type (RR)-WT67-95 group (Table 2, Figure 2A)
Responsiveness of WTs to neoadjuvant chemotherapy is considered for risk and treatment stratification in the Society of Paediatric Oncology (SIOP) studies, with completely necrotic (CN)-WT classified as low-risk and regressive type WT (RT-WT) as intermediate-risk tumors

Summary

Introduction

The outcomes for patients with Wilms' tumors (WTs) have significantly improved over the last decades, with >90% overall survival for those with localized, and 80% for those with metastatic nonanaplastic WT.[1,2,3] It is increasingly important to refine the risk groups and find prognostic factors which identify WT subgroups requiring more aggressive treatment, as well as those who need less treatment to reduce the long-term sequelae and improve patients' quality of life. In the Children's Oncology Group (COG) trials and studies, a selected group of patients with stage I WTs which are regarded as very lowrisk WTs are treated with surgery only.[4,5]. In the International Society of Paediatric Oncology (SIOP) Nephroblastoma Trials and Studies, preoperative chemotherapy has been used in the treatment of WTs and responsiveness to preoperative chemotherapy has been considered for tumor risk and treatment stratification. The SIOP 9 study has demonstrated that completely necrotic WTs (CN-WTs) had a significantly better prognosis than other subtypes[6] and they have been moved to the low-risk group in the subsequent SIOP classifications.[7,8] The regressive type WT (RT-WT), defined as WTs showing 67%-99% of chemotherapy-induced changes (CIC), has been placed in the intermediate-risk group.[8]

Objectives

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Conclusion