Cellular kinetics of neuroblastoma and the role of surgery

Neuroblastoma is known for its peculiar cellular kinetics, which has provoked some controversy regarding surgical treatment. Highly sensitive exploration systems using reverse transcription polymerase chain reaction (RT-PCR) methods have been developed to detect neuroblastoma cells. In our series of 49 patients with advanced neuroblastoma, circulating tumor cells (CTC) were detected by this system in 55.6% of the stage 4 patients who were examined, suggesting that the primary lesion may release tumor cells into the peripheral blood. The Kaplan-Meier survival rate was significantly lower among the patients with CTC or chemotherapy-insensitive bone marrow micrometastasis, compared with those without detectable micrometastasis (33.8 vs. 87.5%, P < 0.05). In contrast, a stage 3 patient with MYCN amplification exhibited drastic local relapse without systemic dissemination of the disease. Two patients were positive for CTC without an identifiable primary site. These observations indicate that the local growth of the primary tumor and tumor cell dissemination may be regulated by different molecular mechanisms in neuroblastomas. MYCN amplification seemed to be more closely associated with localized tumor growth but was minimally correlated with CTC positivity. High-risk neuroblastoma may include two separate subgroups characterized by different cellular kinetics: a local risk cohort and a systemic risk cohort. Surgical strategies for neuroblastoma should be determined with taking this cellular kinetics into consideration.