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Biologic Variables in the Outcome of Stages I and II Neuroblastoma Treated With Surgery as Primary Therapy: A Children’s Cancer Group Study

From the Departments of Surgery, Preventive Medicine, Pediatrics, and Pathology, University of Southern California School of Medicine and Children’s Hospital, Los Angeles; Department of Pediatrics, University of California School of Medicine, San Francisco; and Children’s Cancer Group Operations Center, Arcadia, CA; Department of Surgery, Children’s Hospital, Denver, CO; and Department of Pediatrics, Vanderbilt University, Nashville, TN.

Address reprint requests to Katherine K. Matthay, MD, Children’s Cancer Group, PO Box 60012, Arcadia, CA 91066-6012; email katekm{at}itsa.ucsf.edu

PURPOSE: To determine prospectively whether surgery alone is sufficient therapy for Evans stages I and II neuroblastoma and to define biologic and clinical features having prognostic potential for this group.

PATIENTS AND METHODS: Between June 1989 and August 1995, 374 eligible children (age range, 0 to 18 years) with newly diagnosed stage I (n = 141) and stage II (n = 233) neuroblastoma were registered onto Children’s Cancer Group trial 3881. Surgical resection was the only primary therapy except in cases with spinal cord compression, where radiation therapy was allowed. Event-free survival (EFS) and overall survival (OS) were analyzed by life-table methods according to clinical and biologic features.

RESULTS: EFS and OS (mean ± SE) for all stage I patients were 93% ± 3.0% and 99% ± 1.0%, respectively, compared with 81% ± 4.0% and 98% ± 2.0%, respectively, for stage II patients. The significantly higher recurrence rate among stage II patients was managed successfully in 38 of 43 children with either surgery or multimodality treatment. There was one death among stage I patients and six among stage II. For stage II patients tumor MYCN gene amplication, unfavorable histopathology, an age greater than 2 years, and positive lymph nodes predicted a lower OS (P < .05).

CONCLUSION: Children with stages I and II neuroblastoma have 98% survival with surgery alone as primary therapy. Supplemental treatment was necessary in only 10% of stage I patients and 20% of stage II patients. In children with localized neuroblastoma, a subset of patients that are at higher risk for death can be defined as those with stage II disease who have tumor MYCN amplification or who are 2 years of age with either unfavorable histopathology or positive lymph nodes.

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