ArticlesEffectiveness of screening for neuroblastoma at 6 months of age: a retrospective population-based cohort study
Introduction
Neuroblastoma is one of the most common extracranial solid tumours in childhood. It has been shown to affect one in 7000 children in a non-screening period and to account for about 15% of cancer mortality in children.1, 2 Its prognosis depends on the age and stage of disease at diagnosis. Localised tumours that are diagnosed before 1 year of age have a favourable prognosis, whereas cure of disseminated tumours in children older than 1 year remains difficult despite recent advances in treatment. Since most neuroblastomas produce catecholamines, their metabolites—vanillylmandelic acid and homovanillic acid—can be measured in urine samples to allow early detection of preclinical tumours in infancy.3, 4 Therefore, mass-screening tests for neuroblastoma at 6 months of age were initiated in Kyoto in 1973, and launched nationwide across Japan in 1984–85.5 Mass screening was also introduced in other countries.6, 7, 8, 9, 10 Japan's programme initially used a qualitative test for vanillylmandelic acid in urine, but in 1990 this test was replaced by quantitative measurements with high-performance liquid chromatography (HPLC).4, 11, 12
However, the Japanese mass-screening programme tended to overdiagnose localised tumours with favourable prognoses, including occult tumours that spontaneously regressed or matured without ever becoming clinically overt.13, 14, 15, 16 In 2003, after two reports that screening of infants did not reduce mortality due to neuroblastoma,17, 18 the Japanese government decided to halt screening, on the condition that rates of incidence and mortality should be assessed. We aimed to assess the effectiveness of the Japanese 6-month screening programme, by investigating the incidence of neuroblastoma diagnosed in children younger than 6 years of age, and the associated mortality rates.
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Study participants
We analysed all livebirths between 1980 and 1998 in Japan, excluding those in 1984–85 when compliance with neuroblastoma screening was still low (table 1). We divided these children into three cohorts: children born between 1980 and 1983, when few infants were screened (n=6 130 423); children born between 1986 and 1989, during nationwide qualitative screening (n=5 290 412); and children born between 1990 and 1998, after introduction of the quantitative HPLC screening method (n=10 868 860). The
Results
In the three cohorts, with 22 289 695 children, 3181 children with cases of neuroblastoma that were diagnosed at younger than 72 months of age were registered (table 2). Of these cases, 266 were diagnosed at younger than 6 months and 2915 were diagnosed between 6 and 72 months of age. Compliance rates for quantitative screening were higher than were those for qualitative screening (table 1). 430 neuroblastomas were detected and registered by positive results from qualitative screening, and 1537
Discussion
According to two well-known reports17, 18 screening did not reduce mortality from neuroblastoma, and was associated with a high incidence of early-stage disease. Previous reports from Japan had noted that the incidence of early-stage neuroblastoma was higher in screened infants, but that mortality was lower.13, 23 We analysed a nationwide Japanese cohort, with more than 13 million screened infants, and showed that mortality was lower in those who were screened than in those born before the
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