Impact of Number of Lymph Nodes Sampled and Density of Positive Nodes on Outcomes Among Over 2000 Patients With Stage I to III Favorable Histology Wilms Tumor Enrolled on AREN03B2

OBJECTIVE: To determine whether the number of lymph nodes (LNs) sampled, LN positivity, and LN density impact event-free survival (EFS) or overall survival (OS) in patients with favorable histology Wilms tumor (FHWT). BACKGROUND: LN sampling is a core component of the surgical staging used to assign appropriate therapy in FHWT. LN sampling has also been independently associated with decreased recurrence and improved survival in FHWT. METHODS: Patients with stage I to III FHWT enrolled on the Children's Oncology Group AREN03B2 study with upfront nephrectomy, confirmed LN sampling, and available follow-up and treatment data were included. Cox proportional hazards models with restricted cubic splines were used to visualize the effects of each continuous LN variable on the outcome. RESULTS: A total of 2310 patients met the inclusion criteria. Among stage I to III LN-negative patients, the number of LNs sampled was associated with OS (P=0.001) but did not impact EFS or vary by stage. In stage III LN-positive patients, neither the number of positive LNs nor LN density was associated with EFS or OS. EFS was significantly worse in stage III patients with LN-positive disease (LN-negative 4 y EFS: 93.7%, LN-positive 4 y EFS: 87.2%; P=0.0079), but OS did not differ significantly (LN-negative 4 y OS: 97.0%, LN-positive 4 y OS: 96.8%; P=0.61). CONCLUSION: While this analysis confirmed the negative prognostic impact of LN positivity on EFS and the association of OS and the number of LN sampled, these findings strongly underscore the need for standardized approaches to nodal sampling in FHWT. Such standardization is ongoing in current COG renal tumor trials.