Effectiveness of Nationwide Screening Program for Neuroblastoma in Japan
- Akinori Hisashige
- . for the NBS Evaluation Group
Background: Neuroblastoma (NB) is one of the most malignant neoplasms in childhood. In Japan, while a nationwide screening program at six months of age was introduced in 1985, its efficacy has not been systematically evaluated before or after its introduction. The screening test was changed from a qualitative method to a quantitative method (i.e., high performance liquid chromatography, HPLC) with higher test precision around 1990. However, the Japanese government stopped the program in 2003, after reports which did not show a reduction in mortality from NB. To evaluate the effectiveness of the program, a systematic large-scale epidemiological study was conducted.
Methods: A retrospective cohort study was carried out to evaluate the effectiveness of the NB screening with HPLC test at 6 months of age in Japan, in comparing mortality and incidence of NB after 6 months of age between screened children and concurrent non-screened children in the same area. The study cohort was defined retrospectively as those children who were born after the introduction of HPLC test, from its earliest introduction of January 1984 to December 31, 1997, in twenty-five prefectures of Japan, which cover approximately half of the newborn population of Japan.
Results: The study cohort consisted of 4.31 million. We identified 66 NB deaths in the study cohort for the analysis after 6 months. Kaplan-Meier estimate of cumulative mortality of NB per million children at 6 years was 15.33 for the screened group and 32.63 for the non-screened group, respectively. The difference of hazard between the two groups was statistically significant. The age specific mortality rate ratio of NB (95% confidence interval (CI)) was statistically lower at 1 - 3 years [0.415 (0.212 - 0.810)]. The rate ratio of NB incidence (95% CI) at the early stage (i.e., 1, 2 and 4S) between them was statistically higher at 6 months - 1 year [9.56 (4.76 - 19.23)]. That of NB incidence at the advanced stage (i.e., 3 and 4) was statistically lower at 1 - 4 years [0.40 (0.26 - 0.62)].
Conclusion: The present study showed the reduction of mortality from NB, as well as the increase of the identification of early stage of NB and the decrease of advanced stage of NB. These findings strongly suggest the effectiveness of the NB screening with HPLC test in Japan. Although there could be several biases inherent to the study design, their possibilities are considered to be relatively low from observational information and theoretical consideration.
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