Wilms' tumour. Optimal treatment strategies.

Wilms' tumour (WT) is the most common renal tumour in children. Much progress has been made in the management of patients with this malignancy over the last 3 decades. The improved outcome has mainly resulted from the availability of cooperative national and international trials involving the National Wilms' Tumour Study Group (NWTS) and the International Society of Paediatric Oncology (SIOP). These groups have focused on optimising postoperative (NWTS) and preoperative (SIOP) therapy, respectively. The early studies by the NWTS (1 and 2) identified the following separate subgroups of patients (based on age and stage) that benefited either from the addition of irradiation to postoperative chemotherapy or from combination chemotherapy as opposed to single agents, and those patients who did not benefit from prolonged chemotherapy administration. Additionally, these studies identified histologic features associated with a poor outcome. The more recent studies by NWTS (3 and 4) concentrated on reducing treatment for low risk patients to avoid long term sequelae while intensifying therapy for patients with high risk features, such as those with unfavourable histology and/or metastatic disease. The early SIOP trials (1, 2 and 5) concluded that patients treated with preoperative therapy (chemotherapy alone or combined with irradiation) experienced fewer intraoperative tumour ruptures compared with patients who had immediate surgery. However, preoperative chemotherapy preserved tumour histology at surgical exploration better than preoperative irradiation. The more recent SIOP trials (6, 9 and 93-01) have compared the use of different preoperative treatment regimens as well as the intensity and duration of postoperative therapy based on prognostic features (stage and histology). These studies have also identified groups benefiting from the addition of irradiation and/or the use of a third chemotherapeutic agent. Bilateral WT occurs in a small percentage of patients and treatment strategies, although efficacious, are limited by the need to maximise residual renal parenchyma. Recurrent WT occurs in 10 to 15% of cases and although a proportion of patients are curable, the overall outcome is poor with 3-year survival being in the range of 30%. There are several ongoing studies utilising new drug combinations (carboplatin, cyclophosphamide and etoposide) attempting to improve the outcome for these patients. Overall, the majority of patients with WT will be cured and become long term survivors. Cooperative group studies continue to address the issue of minimising long term morbidity for low risk patients while maximising outcome for high risk patients.