Purpose Wilms tumor is a common renal cancer of childhood with long-term survival rates exceeding 80% in high-resource countries, yet survival remains below 50% in the low-resource settings of Africa. We assessed outcomes of a resource-adapted treatment protocol at a Malawian hospital to identify actionable factors affecting survival. Methods: We assessed clinical outcomes with a single-center retrospective cohort study of children diagnosed between 2016 and 2021 in Lilongwe, Malawi. Findings: We identified 136 patients with Wilms tumor, most commonly with stage III (25.7%) or IV disease (25.7%). Two-year overall survival (OS) was: Stage I, 78%; Stage II, 27%; Stage III, 62%; Stage IV, 23%, Stage V, 0%. Event-free survival (EFS) was: Stage I, 60%; Stage II, 0%; Stage III, 51%; Stage IV, 13%; Stage V, 0%. After death, treatment abandonment was the most common event comprising EFS, occurring in 26.5% of patients. Among 43% of patients who completed therapy, 2-year OS was 80% and EFS was 69%. Relapse was documented in 9.6% of patients. Radiotherapy was indicated for 40.4% patients, among whom only three received it due to regional unavailability. Factors associated with OS were severe acute malnutrition (Hazard ratio, HR, 1.9), increasing tumor stage (HR, 1.5), and inferior vena cava involvement (HR, 2.7). On multivariable analysis, only tumor stage remained associated with outcome. Interpretation Implementing a curative resource-adapted treatment protocol in an extremely resourced-constrained environment was feasible in Malawi and resulted in relatively favorable outcomes in low-stage disease, particularly among those who completed therapy. However, factors such as late-stage disease, frequent abandonment, and absent radiotherapy represent ongoing implementation barriers that should be the focus of continued research funding and intervention in Africa.

Introduction: Wilms tumor therapy in low-and middle-income countries (LMICs) relies on treatment protocols adapted to resource limitations, but these protocols have rarely been evaluated in real-world settings. Such evaluations are necessary to identify high-impact research priorities for clinical and implementation trials in LMICs. The purpose of this study was to identify highest priority targets for future clinical and implementation trials in sub-Saharan Africa by assessing outcomes of a resource-adapted treatment protocol in Malawi. Methods: We conducted a retrospective cohort study of children treated for Wilms tumor with an adapted SIOP-backbone protocol in Lilongwe, Malawi between 2016 and 2021. Survival analysis assessed variables associated with poor outcome with high potential for future research and intervention. Results: We identified 136 patients, most commonly with stage III (n = 35; 25.7%) orIV disease (n = 35; 25.7%). Two-year event-free survival (EFS) was 54% for stage I/II, 51% for stage III, and 13% for stage IV. A single patient with stage V disease survived to 1 year. Treatment abandonment occurred in 36 (26.5%) patients. Radiotherapy was indicated for 55 (40.4%), among whom three received it. Of these 55 patients, 2-year EFS was 31%. Of 14 patients with persistent metastatic pulmonary disease at the time of nephrectomy, none survived to 2 years. Notable variables independently associated with survival were severe acute malnutrition (hazard ratio [HR]: 1.9), increasing tumor stage (HR: 1.5), and vena cava involvement (HR: 3.1). Conclusion:High-impact targets for clinical and implementation trials in low-resource settings include treatment abandonment, late presentation, and approaches optimized for healthcare systems with persistently unavailable radiotherapy.