title: Effectiveness of screening for neuroblastoma at 6 months of age: a retrospective population-based cohort study.
abstract: BACKGROUND
  In Japan, a nationwide programme between 1984 and 2003 screened all infants for urinary catecholamine metabolites as a marker for neuroblastoma. Before 1989, this was done by qualitative spot tests for vanillylmandelic acid in urine, and subsequently by quantitative assay with high-performance liquid chromatography (HPLC). However, the Japanese government stopped the mass-screening programme in 2003, after reports that it did not reduce mortality due to neuroblastoma. We aimed to assess the effectiveness of the programme, by comparing the rates of incidence and mortality from neuroblastomas diagnosed before 6 years of age in three cohorts.
  
  
  METHODS
  We did a retrospective population-based cohort study on all children born between 1980 and 1998, except for a 2-year period from 1984. We divided these 22,289,695 children into three cohorts: children born before screening in 1980-83 (n=6,130,423); those born during qualitative screening in 1986-89 (n=5,290,412); and those born during quantitative screening 1990-98 (n=10,868,860). We used databases from hospitals, screening centres, and national cancer registries. Cases of neuroblastoma were followed up for a mean of 78.7 months.
  
  
  RESULTS
  21.56 cases of neuroblastoma per 100,000 births over 72 months were identified in the qualitatively screened group (relative risk [RR] 1.87, 95% CI 1.66-2.10), and 29.80 cases per 100,000 births over 72 months in the quantitatively screened group (RR 2.58, 2.33-2.86). The cumulative incidence of neuroblastoma in the prescreening cohort (11.56 cases per 100,000 births over 72 months) was lower than that in other cohorts (p<0.0001 for all comparisons), but more neuroblastomas were diagnosed after 24 months of age in this cohort (p=0.0002 for qualitative screening vs prescreening, p<0.0001 for quantitative screening vs prescreening). Cumulative mortality was lower in the qualitative screening (3.90 cases per 100,000 livebirths over 72 months) and quantitative screening cohorts (2.83 cases) than in the prescreening cohort (5.38 cases). Compared with the prescreening cohort, the relative risk of mortality was 0.73 (95% CI 0.58-0.90) for qualitative screening, and 0.53 (0.42-0.63) for quantitative screening. Mortality rates for both the qualitative and quantitative screening groups were lower than were those for the prescreening cohort (p=0.0041 for prescreening vs qualitative screening, p<0.0001 for prescreening vs quantitative screening).
  
  
  CONCLUSIONS
  More infantile neuroblastomas were recorded in children who were screened for neuroblastoma at 6 months of age than in those who were not. The mortality rate from neuroblastoma in children who were screened at 6 months was lower than that in the prescreening cohort, especially in children screened by quantitative HPLC. Any new screening programme should aim to decrease mortality, but also to minimise overdiagnosis of tumours with favourable prognoses (eg, by screening children at 18 months).
authors.affiliation: Department of Paediatric Surgery, Hiroshima University Hospital, Hiroshima, Japan. eiso@hiroshima-u.ac.jp
authors.forename: Eiso
authors.initials: E
authors.lastname: Hiyama
authors.forename: Tomoko
authors.initials: T
authors.lastname: Iehara
authors.forename: Tohru
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukuzawa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Sasaki
authors.forename: Masahiko
authors.initials: M
authors.lastname: Sugiyama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kondo
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yoneda
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yamaoka
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Tajiri
authors.forename: Kohei
authors.initials: K
authors.lastname: Akazawa
authors.forename: Megu
authors.initials: M
authors.lastname: Ohtaki
mesh_terms: D000328:Adult; D017677:Age Distribution; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005188:False Negative Reactions; D005858:Germany / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007223:Infant; D007564:Japan / Q000453:epidemiology; D008403:Mass Screening / Q000379:methods / Q000706:statistics & numerical data*; D008875:Middle Aged; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000175:diagnosis* / Q000453:epidemiology / Q000473:pathology / Q000517:prevention & control* / Q000556:secondary; D016730:Program Development; D011792:Quebec / Q000453:epidemiology; D012189:Retrospective Studies; D015996:Survival Rate