“In intensively treated patients with stage IV neuroblastoma age 18 months or older at diagnosis, surgery of the primary tumor site has no impact on local control rate and outcome,” according to findings from the German prospective clinical trial NB97. “The results of the study,” the researchers concluded in an article in the Journal of Clinical Oncology, “do not justify aggressive surgery in patients undergoing high-intensity multimodal treatment for metastatic neuroblastoma. Thus, the concept of accepting incomplete resection to avoid serious complications proved successful, as evidenced by analyses of the data from the NB97 trial.”
Study Details
NB97 was a randomized trial comparing autologous stem-cell transplantation and oral maintenance therapy. Data on extent and complications of resection were collected prospectively. The researchers distinguished between two types of operations: “first operation was the tumor operation performed before induction chemotherapy, and best operation was the most extensive removal of primary tumor tissue done at any time during first-line therapy.”
The data from 278 patients who had stage IV neuroblastoma and were 18 months or older showed that whether patients had complete resection, incomplete resection, biopsy, or no surgery before chemotherapy, the “extent of first operation had no impact on event-free survival (P = .207), local progression–free survival (P = .195), and overall survival (P = .351),” the researchers reported. “After induction chemotherapy, 54.7% of patients underwent complete resection of the primary tumor, 30.6% underwent incomplete resection, and 13.3% had only biopsy or no surgery of the primary tumor,” they continued.
The most extensive removal of primary tumor tissue was done during the first operation in 61 patients (21.9%) and later in 212 patients (76.3%). “The extent of best operation also had no impact on [event-free survival] (P = .877), [local progression–free survival] (P = .299), and [overall survival] (P = .778),” the investigators stated. “Moreover, multivariate analyses showed that surgery did not affect [event-free, local progression–free, and overall] survival.”
Adverse Events
Complications during surgery occurred among 64 patients (23%). “At first operation, 16 patients developed relevant intraoperative bleeding (5.8%), nine patients had intestinal obstruction after resection of abdominal neuroblastoma (3.2%), and nine patients experienced postoperative local or systemic infections (3.2%),” the researchers reported. Although the trial protocol discouraged nephrectomy, it was performed in eight patients during first operation (2.9%) and in 18 patients (6.5%) during best operation. “During best operation, relevant bleeding occurred in 26 patients (9.4%), postoperative intestinal obstruction occurred in 14 patients (5.0%), and postoperative local or systemic infections occurred in 17 patients (6.1%). Nephrectomy was performed in 18 patients (6.5%),” the investigators wrote.
“Combining the results of this study with those from the literature clearly shows that aggressive surgery has a limited impact, if any, on the outcome of high-risk neuroblastoma,” the researchers concluded. “However, future trials are required to determine whether even less surgery might be adequate in high-intensity multimodal treatment of metastatic neuroblastoma and if biologic factors are correlated with the resectability of the primary tumor.” ■
Simon T, et al: J Clin Oncol. January 2, 2013 (early release online).
