Abstract 4520: Assessing treatment strategies in high-risk metastatic nephroblastoma: A trinetx-based comparison of chemotherapy with surgery vs. primary nephrectomy

Abstract Introduction: Wilms Tumor, or nephroblastoma, is the most prevalent kidney cancer in pediatric populations. With a survival probability nearing 90%, the disease carries a 15% risk of recurrence. Wilms Tumor has a developmental origin, frequently involving mutations in genes such as WT1, WTX, CTNNB1, and TP53, which correlate with a poorer prognosis. The tumor can present unilaterally or bilaterally, often due to excess metanephric tissue cultures. Despite favorable survival rates, the potential for recurrence and malignancy calls for continuous evaluation of treatment strategies. Methods: A retrospective analysis was conducted on patients aged 0-18 diagnosed with Wilms Tumor and treated either by chemotherapy followed by surgery (Cohort 1) or surgery alone (Cohort 2). Cohort 1 included 289 patients who underwent chemotherapy prior to nephrectomy, while Cohort 2 consisted of 84 patients who received only a partial or full nephrectomy. Outcomes were compared over a 10-year follow-up period, focusing on secondary malignancies and survival rates. Results: Over the 10-year follow-up, Cohort 2 (surgery-only) demonstrated a significantly higher survival probability compared to Cohort 1 (chemotherapy plus surgery). The risk of a secondary malignancy was 97.23% in Cohort 1, compared to 73.8% in Cohort 2, indicating a 12.4% increase in malignancy risk with the addition of chemotherapy (p < 0.0001). This data suggests that chemotherapy prior to surgery may not be the safest option in terms of long-term outcomes for nephroblastoma patients. Conclusion: Current nephroblastoma treatment involves chemotherapy followed by surgical resection. Our study suggests that surgery alone may provide better outcomes, reducing the risk of secondary malignancies by 12.4% and significantly improving long-term survival. While surgical excision alone may not be feasible in all cases, it warrants consideration as an individualized treatment option. Further research should investigate nephrectomy-only treatment as a potentially safer and more effective alternative for pediatric Wilms Tumor patients. Citation Format: Zayan Musa, Javier Prieto, Fatemeh Adabifirouzjaei. Assessing treatment strategies in high-risk metastatic nephroblastoma: A trinetx-based comparison of chemotherapy with surgery vs. primary nephrectomy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4520.