Includes bibliographical references (leaves 78-96).BACKGROUND: In Africa Wilms' tumour frequently presents with advanced disease. This study reports our results over 25 years using the National Wilms' Tumor Study Group approach of primary surgery, in the form of nephrectomy, followed by chemotherapy. A small number of these tumours are bilateral and here surgery has evolved from simple nephrectomy into the use of nephron-sparing techniques. METHODS: A retrospective analysis was performed on all patients diagnosed with Wilms' tumour between January 1979 and December 2003. Treatment was according to National Wilms' Tumor Study Group protocols. For unilateral Wilms' tumour primary surgery, where possible, was followed by adjuvant chemotherapy with vincristine and dactinomycin. Doxorubicin was added for stage III and IV tumours. Other drugs were used for unfavourable histology, and radiotherapy was reserved for local stage III tumours and pulmonary metastases. Patients with bilateral Wilms' tumours underwent initial bilateral biopsy, neoadjuvant chemotherapy and tumourectomy. Where indicated, nephrectomy (partial or complete) involved using ice dam topical cooling and vascular control, and in one case bench surgery and extensive renal reconstruction with orthotopic autotransplantation. Revision tumourectomy was utilized on three occasions for recurrence in areas of nephroblastomatosis. Radiotherapy was reserved for pulmonary metastases and palliation. RESULTS: There were 188 children with unilateral Wilms' tumour and 20 with bilateral Wilms' tumour. Among those with unilateral Wilms' tumour fifty seven (30.3%) were stage I, 33 (17.6%) were stage II, 60 (31.9%) were stage III and 38 (20.2%) were stage IV. Twenty-four patients (12.8%) had unfavourable histology. Fifteen of the bilateral Wilms' tumours had a synchronous presentation, one with liver metastases at diagnosis, and five were metachronous. Nephroblastomatosis was identified in 18 of the 20 patients (90%) with bilateral Wilms' tumour. One hundred and forty five patients are alive and disease free, 23 to 318 months from diagnosis. The estimated 5-year overall survival for all unilateral Wilms' tumours was 78.3%; 82.8% for favourable histology and 47.3% for unfavourable histology. Among those with favourable histology, estimated 5-year overall survival was 94.6% for stage I, 96.2% for stage II, 78.4% for stage III and 54.2% for stage IV. There was no difference in overall survival between those favourable histology stage III tumours that were operable and those deemed inoperable. Intra-operative spillage was uncommon (8%), and did not increase local relapse rate. Survival of stage IV disease has not improved over the last decade. mong those with bilateral Wilms' tumours, 11 are alive free of disease one to fifteen years after completing treatment, all with well-preserved renal function. Nine have died (two of unrelated disease), including six of the seven with spread outside the kidney. All three with unfavourable histology are alive, as are four of the five with a metachronous presentation. Survival for bilateral Wilms' tumour has improved markedly in the last decade. CONCLUSIONS AND RECOMMENDATIONS" National Wilms' Tumor Study Group protocols employed in a South African setting with highly competent and experienced surgical care, produced results for non-metastatic favourable histology unilateral Wilms' tumour comparable to those of the National Wilms' Tumor Study Group. For bilateral Wilms' tumours appropriate chemotherapy together with conservative (nephron-sparing) and innovative surgery produced good results with preservation of adequate renal function in nearly all cases. We can seek to improve outcomes via better risk stratification with molecular markers, new adjuvant chemotherapy regimes for high risk tumours and novel surgical approaches to improve nephron-sparing in bilateral Wilms' tumour. Improving results in Stage IV patients may depend as much on earlier diagnosis, as on advances in therapeutics
