Is extensive surgery required for treatment of advanced neuroblastoma?
BACKGROUND: Prognosis of advanced neuroblastoma is still disappointing although recently slightly improving because of more intensive chemotherapy supported with stem cell transfusion. Before 1985, all patients at University of Tsukuba over the age of 1 year who had stage III and IV neuroblastoma died regardless of extensive resection of the primary tumor. METHODS: Since the treatment protocol of the Study Group of Japan for Advanced Neuroblastoma was introduced in 1985, the authors treated 14 consecutive patients over the age of 1 year who had advanced neuroblastoma with six to eight cycles of the intensive induction chemotherapy regimens followed by resection of the primary and local lymph node metastasis combined with intraoperative irradiation. The resection of the primary tumor and the lymph node metastasis was much less extensive preserving adventitia with perivascular nerves to avoid postoperative vascular occlusion, intestinal dysmotility, and massive lymphorrhea, which interfere with postoperative intensive chemotherapy. If the dissection of lymph nodes from major vessels was difficult, the authors intentionally left the tumor-containing lymph nodes. RESULTS: There were macroscopic residual tumors in 8 of 14 patients. Electron beam irradiation, 10 to 15 Gy, was given to the tumor bed intraoperatively. Overall survival of these 14 patients was 63% (eight patients) at 5 years with six patients surviving without recurrence for more than 5 years. Five patients died of tumors, two of whom died before surgery. Local tumor control failed in only two patients. In one patient, the tumor recurred twice 47 months and 61 months after therapy. After undergoing a second resection at 69 months, this child has survived tumor free for 12 months after the second recurrence. The other patient who had tumor recurrence had an N-myc-amplified tumor that recurred 4 months postoperatively in the hepatoduodenal ligament locally with massive bone metastasis. The 5-year local relapse-free probability for patients with stage III and IV tumors who had an operation was 79% by the Kaplan-Meier method. CONCLUSION: Systematic extensive surgery for advanced or metastatic neuroblastoma is no longer required if supplemented with intensive pre- and postoperative chemotherapy with intraoperative radiotherapy.