Results of the Third AIEOP Cooperative Protocol on Wilms Tumor (TW2003) and Related Considerations

Purpose TW2003, the third Italian prospective study on Wilms tumor, aimed to improve survival in patients with stage III-IV tumors, de-escalate therapy for stage I-II nonanaplastic tumors, refine the risk stratification of therapy, and develop a national infrastructure for biobanking and central pathology review. Materials and Methods TW2003 recruited children 18 years old or younger with primary intrarenal tumors. Local physicians chose nephrectomy with or without preoperative chemotherapy as the initial treatment based on the risk of unsafe and/or incomplete immediate surgery. The main drivers for adjuvant therapy were tumor stage and diffuse anaplasia. A new risk stratification schema was investigated, incorporating patient age, reason for stage III designation and completeness of lung nodule response in stage IV disease. Results We report on 453 patients with unilateral Wilms tumor. Preoperative chemotherapy was administered to 42% of patients. The 5-year event-free survival and overall survival rates were 89.1% (95% CI 83.6–94.9) and 97.0% (93.7–100) for stage I; 85.1% (79.6–91.1) and 94.0% (90.1–98.1) for stage II (160); 82.7% (75.3–90.8) and 90.9% (85.0–97.1) for stage III (101); and 72.1% (61.9–84.0) and 82.5% (73.1–93.1) for stage IV (69), respectively. On multivariable analysis only anaplasia was significant for event-free survival (HR 2.68, 95% CI 1.48–4.86, p=0.001; bias corrected c-index 0.580) and overall survival (HR 5.29, 95% CI 2.52–11.12, p <0.001; bias corrected c-index 0.697). Conclusions The survival rates achieved and the proposed risk stratification schema provide a basis for future comparisons of Wilms tumor treatment burden and patient outcome.