title: Prevalence of Metastasis at Diagnosis of Osteosarcoma: An International Comparison.
abstract: BACKGROUND
  Osteosarcoma (OS) is the most common primary malignant bone tumor in many countries, with metastatic disease responsible for most patient deaths. This study compares the prevalence of metastatic OS at diagnosis across countries to inform the critical question of whether diagnostic delay or tumor biology drives metastases development prior to diagnosis.
  
  
  METHODS
  A literature search of the PubMed database was conducted to compare the prevalence of metastatic disease at the time of OS diagnosis between countries. A pooled prevalence with 95% confidence intervals was calculated for each study meeting inclusion criteria. Studies were grouped for analysis based on human development index (HDI) scores.
  
  
  RESULTS
  Our analysis found an 18% (95% confidence interval [CI]: 15%, 20%) average global pooled proportion of metastasis at OS diagnosis. The average prevalence of metastasis at diagnosis increased as HDI groupings decreased, with very high HDI, high HDI, and medium/low HDI groups found to be 15% (95% CI: 13%, 17%), 20% (95% CI: 14%, 28%), and 31% (95% CI: 15%, 52%), respectively.
  
  
  CONCLUSIONS
  Our evidence suggests there is a biological baseline for metastatic OS at diagnosis, which is observed in countries with very high HDI. In countries with medium/low HDI, where there are more barriers to accessing healthcare, the higher prevalence of metastasis may result from treatment delay or an artificial prevalence inflation due to patients with less severe symptoms not presenting to clinic. Additional research in countries with medium/low HDI may reveal that earlier detection and treatment could improve patient outcomes in those countries.
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Tracy A
authors.initials: TA
authors.lastname: Marko
authors.affiliation: School of Public Health, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Diessner
authors.affiliation: Department of Pediatric Epidemiology, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Logan G
authors.initials: LG
authors.lastname: Spector
mesh_terms: D001859:Bone Neoplasms / Q000473:pathology*; D057210:Delayed Diagnosis / Q000009:adverse effects*; D003906:Developing Countries; D006801:Humans; D009362:Neoplasm Metastasis; D012516:Osteosarcoma / Q000453:epidemiology* / Q000473:pathology*; D015995:Prevalence; D012959:Socioeconomic Factors
keywords: bone cancer; epidemiology; human development index; metastasis; osteosarcoma