title: Cancer Incidence after Initiation of Antimuscarinic Medications for Overactive Bladder in the United Kingdom: Evidence for Protopathic Bias.
abstract: OBJECTIVE
  To estimate the incidence of 10 common cancers among patients treated with antimuscarinic medications for overactive bladder (AMOABs).
  
  
  METHODS
  Retrospective cohort study.
  
  
  METHODS
  United Kingdom's Clinical Practice Research Datalink.
  
  
  METHODS
  A total of 119,912 adults with no previous cancer diagnosis who were new users of AMOABs-darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, or trospium-between January 2004 and December 2012.
  
  
  RESULTS
  Sex-specific incidence rates per 1000 person-years and 95% confidence intervals (CIs) were estimated for each study cancer (bladder, breast, colorectal, lung, melanoma, non-Hodgkin lymphoma, pancreatic, prostate, renal, and uterine cancer) overall and stratified by time since cohort entry and by cumulative AMOAB dose. Among the 119,912 patients followed for 399,365 person-years, 4117 incident study cancers occurred. The incidence rate of prostate cancer was 14.2 (95% CI 12.9-15.5) in the year after cohort entry and decreased markedly thereafter. The incidence rate of bladder cancer was also higher in the year after cohort entry than subsequently (men: 5.5, 95% CI 4.8-6.4; women: 1.2, 95% CI 1.0-1.5). The incidence rates of both prostate and bladder cancer decreased with increasing cumulative dose of AMOAB. We observed no similar relations between incidence rates of other study cancers and time since cohort entry.
  
  
  CONCLUSIONS
  High incidence rates of bladder and prostate cancer soon after AMOAB initiation and a negative correlation between incidence and cumulative AMOAB dose suggest that protopathic bias is a more likely explanation for these findings than causality. (Protopathic bias in this context means patients' urinary symptoms prompted treatment with an AMOAB, but the symptoms were actually due to a cancer that was already present, although not yet diagnosed or not yet recorded.) To avoid unnecessary delays in the diagnosis of prostate and bladder cancer, physicians should consider these diseases in patients for whom treatment with AMOABs is indicated.
authors.affiliation: Epidemiology, RTI Health Solutions, Waltham, Massachusetts.
authors.forename: James A
authors.initials: JA
authors.lastname: Kaye
authors.affiliation: Epidemiology, RTI Health Solutions, Barcelona, Spain.
authors.forename: Andrea V
authors.initials: AV
authors.lastname: Margulis
authors.affiliation: Epidemiology, RTI Health Solutions, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Fortuny
authors.affiliation: Epidemiology, Data Analysis, RTI Health Solutions, Durham, North Carolina.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: McQuay
authors.affiliation: Biostatistics, RTI Health Solutions, Barcelona, Spain.
authors.forename: Estel
authors.initials: E
authors.lastname: Plana
authors.affiliation: Biostatistics, RTI Health Solutions, Durham, North Carolina.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Bartsch
authors.affiliation: Epidemiology, RTI Health Solutions, Durham, North Carolina.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Bui
authors.affiliation: Epidemiology, RTI Health Solutions, Barcelona, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Perez-Gutthann
authors.affiliation: Epidemiology, RTI Health Solutions, Barcelona, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Arana
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015982:Bias; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000009:adverse effects*; D009369:Neoplasms / Q000139:chemically induced* / Q000453:epidemiology*; D012189:Retrospective Studies; D006113:United Kingdom / Q000453:epidemiology; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000453:epidemiology*; D055815:Young Adult
chemical_list: D018727:Muscarinic Antagonists
keywords: bladder; cancer; epidemiology; incidence; medications; overactive bladder; prostate