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.

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 2,117 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 EFS and 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 < 0.01) and 95.2% (±0.01%SE, P = 0.59), respectively. CN-WT and STN-WT96-99 groups showed significantly better EFS than RR-WT67-95 (P = 0.003 and P = 0.02, 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. This article is protected by copyright. All rights reserved.