A Halt to Neuroblastoma Screening in Japan

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     To the Editor: Neuroblastoma is the most common form of malignant solid tumor during childhood. Japan is the only country in which mass screening for neuroblastoma has been adopted as a national policy, and the program has been conducted since 1984. In 2001, urine samples from 1,170,662 infants six months of age (90.4 percent of eligible infants of that age in Japan) were tested for homovanillic acid and vanilmandelic acid (metabolites of catecholamines produced by neuroblastoma) by high-performance liquid chromatography, and 180 cases of neuroblastoma were detected.

    The April 4, 2002, issue of the Journal included reports of screening studies in Germany1 and Canada.2 The German study used high-performance liquid chromatography to screen infants one year of age, and the Canadian study used thin-layer chromatography, a less sensitive method, to screen infants three weeks and six months of age. Neither trial found that the screenings were associated with a reduction in the rate of death due to neuroblastoma,1,2 and both resulted in substantial overdiagnosis of cases of neuroblastoma that would not otherwise have become clinically evident.1,3 The findings of the two trials disagreed with those of descriptive and observational studies in Japan that had suggested a reduction in the rate of death due to neuroblastoma in association with the screening of six-month-old infants by high-performance liquid chromatography.4

    Because of these discrepancies, on May 28, 2003, the Japanese Ministry of Health, Labor, and Welfare organized a special committee to reconsider the rationale for the current policy, with one of us serving as the chairman and the other as a member of the committee. After four meetings, the committee published a report on August 14, 2003.5 Concluding that there was sufficient evidence that the current method of screening led to overdiagnosis of neuroblastoma and that there was insufficient evidence that the program reduced the rate of death from the disease, the committee recommended against the continuation of screening in the report. Consequently, the Ministry of Health, Labor, and Welfare decided to halt the program by the end of fiscal year 2003 (March 2004). The Japanese experience with neuroblastoma screening underscores the importance of rigorous evaluation of potential benefit and harm before a screening program is adopted as public policy.

    Yoshitaka Tsubono, M.D.

    Tohoku University Graduate School of Medicine

    Miyagi 980-8575, Japan

    ytsubono@metamedica.com

    Shigeru Hisamichi, M.D.

    Miyagi Cancer Center

    Miyagi 981-1293, Japan

    References

    Schilling FH, Spix C, Berthold F, et al. Neuroblastoma screening at one year of age. N Engl J Med 2002;346:1047-1053.

    Woods WG, Gao RN, Shuster JJ, et al. Screening for infants and mortality due to neuroblastoma. N Engl J Med 2002;346:1041-1046.

    Woods WG, Tuchman M, Robinson LL, et al. A population-based study of the usefulness of screening for neuroblastoma. Lancet 1996;348:1682-1687.

    Nishi M, Miyake H, Takeda T, Hanai J, Kikuchi Y, Takasugi N. Mass screening for neuroblastoma and mortality in birth cohorts. Int J Cancer 1997;71:552-555.

    Report of the special committee on mass screening for neuroblastoma. (In Japanese.) (Accessed April 16, 2004, at http://www.mhlw.go.jp/shingi/2003/08/s0814-2.html.)

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