Influence of Surgical Excision on the Survival of Patients With Stage 4 High-Risk Neuroblastoma: A Report From the HR-NBL1/SIOPEN Study

PURPOSE To evaluate the impact of surgeon-assessed extent of primary tumor resection on local progression and survival in patients in the International Society of Pediatric Oncology Europe Neuroblastoma Group High-Risk Neuroblastoma 1 trial. PATIENTS AND METHODS Patients recruited between 2002 and 2015 with stage 4 disease > 1 year or stage 4/4S withMYCNamplification < 1 year who had completed induction without progression, achieved response criteria for high-dose therapy (HDT), and had no resection before induction were included. Data were collected on the extent of primary tumor excision, severe operative complications, and outcome. RESULTS A total of 1,531 patients were included (median observation time, 6.1 years). Surgeon-assessed extent of resection included complete macroscopic excision (CME) in 1,172 patients (77%) and incomplete macroscopic resection (IME) in 359 (23%). Surgical mortality was 7 (0.46%) of 1,531. Severe operative complications occurred in 142 patients (9.7%), and nephrectomy was performed in 124 (8.8%). Five-year event-free survival (EFS) +/- SE (0.40 +/- 0.01) and overall survival (OS; 0.45 +/- 0.02) were significantly higher with CME compared with IME (5-year EFS, 0.33 +/- 0.03; 5-year OS, 0.37 +/- 0.03;P< .001 andP= .004). The cumulative incidence of local progression (CILP) was significantly lower after CME (0.17 +/- 0.01) compared with IME (0.30 +/- 0.02;P< .001). With immunotherapy, outcomes were still superior with CME versus IME (5-year EFS, 0.47 +/- 0.02v0.39 +/- 0.04;P= .038); CILP was 0.14 +/- 0.01 after CME and 0.27 +/- 0.03 after IME (P< .002). A hazard ratio of 1.3 for EFS associated with IME compared with CME was observed before and after the introduction of immunotherapy (P= .030 andP= .038). CONCLUSION In patients with stage 4 high-risk neuroblastoma who have responded to induction therapy, CME of the primary tumor is associated with improved survival and local control after HDT, local radiotherapy (21 Gy), and immunotherapy.