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Cancer Incidence after Initiation of Antimuscarinic Medications for Overactive Bladder in the United Kingdom: Evidence for Protopathic Bias
Author(s) -
Kaye James A.,
Margulis Andrea V.,
Fortuny Joan,
McQuay Lisa J.,
Plana Estel,
Bartsch Jennifer L.,
Bui Christine L.,
PerezGutthann Susana,
Arana Alejandro
Publication year - 2017
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/phar.1932
Subject(s) - medicine , overactive bladder , cumulative incidence , incidence (geometry) , bladder cancer , cohort , cancer , urology , retrospective cohort study , oncology , prostate cancer , cancer registry , tolterodine , prostate , gynecology , pathology , physics , alternative medicine , optics
Study Objective To estimate the incidence of 10 common cancers among patients treated with antimuscarinic medications for overactive bladder ( AMOABs ). Design Retrospective cohort study. Data Source United Kingdom's Clinical Practice Research Datalink. Patients A total of 119,912 adults with no previous cancer diagnosis who were new users of AMOAB s—darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, or trospium—between January 2004 and December 2012. Measurements and Main Results Sex‐specific incidence rates per 1000 person‐years and 95% confidence intervals ( CI s) 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. Conclusion 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 AMOAB s is indicated.