Environmental and occupational exposures and prognosis in patients with non-muscle-invasive bladder cancer in the Be-Well Study

Our plain-English summary of Environmental and occupational exposures and prognosis in patients with non-muscle-invasive bladder cancer in the Be-Well Study, by Z. Wang, M.L. Kwan, R. Haque, et al (American Journal of Epidemiology, 2024).

The study

• Authors: Z. Wang, M.L. Kwan, R. Haque, R. Pratt, V.S. Lee, J.M. Roh, I.J. Ergas, K.L. Cannavale, R.K. Loo, D.S. Aaronson, C.P. Quesenberry, C.B. Ambrosone, L.H. Kushi, L. Tang
• Journal: American Journal of Epidemiology
• Published: 2024;193(6):863-873
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Bladder cancer is primarily diagnosed as non-muscle-invasive bladder cancer (NMIBC), with high recurrence and progression rates. Environmental and occupational exposures to carcinogens are well-known risk factors for developing bladder cancer, yet their effects on prognosis remain unknown. In the Be-Well Study, a population-based prospective cohort study of 1472 Kaiser Permanente patients newly diagnosed with NMIBC in California from 2015 to 2019, we examined history of environmental and occupational exposures in relation to tumor stage and grade at initial diagnosis by multivariable logistic regression, and subsequent recurrence and progression by Cox proportional hazards regression. Exposure to environmental and occupational carcinogens was significantly associated with increased risk of progression (hazard ratio (HR) = 1.79; 95% CI, 1.04-3.09), specifically with increased progression to muscle-invasive disease (HR = 2.28; 95% CI, 1.16-4.50). Exposures to asbestos and arsenic were associated with increased odds of advanced stage at diagnosis (asbestos: odds ratio (OR) = 1.43 [95% CI, 1.11-1.84]; arsenic: OR = 1.27 [95% CI, 1.01-1.63]), and formaldehyde exposure was associated with increased risk of recurrence (HR = 1.38; 95% CI, 1.12-1.69). Our findings suggest that considering a patient's history of these exposures may benefit current risk stratification systems in better tailoring clinical care and improving prognosis among patients with NMIBC.

© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: [email protected].

In plain English

This study followed 1472 Kaiser Permanente patients in California newly diagnosed with non-muscle-invasive bladder cancer from 2015 to 2019. Soon after diagnosis, patients reported in a telephone interview any past exposure to substances such as asbestos or formaldehyde, or work in certain jobs. 1076 (73.1%) reported some exposure. The article does not report asbestos fiber types or fiber-specific results. Over a median 28 months, 473 patients had a recurrence. In 89 of these the cancer progressed, including 65 that progressed to muscle-invasive cancer. After adjusting for smoking and other factors, any reported exposure was associated with higher risk of progression (hazard ratio 1.79; 95% CI 1.04-3.09) and of progression to muscle-invasive disease (2.28; 1.16-4.50). Reported asbestos exposure was associated with a more advanced tumor stage at diagnosis (odds ratio 1.43; 1.11-1.84). Asbestos exposure of more than 5 years was associated with recurrence (hazard ratio 1.29; 1.01-1.66). Formaldehyde was associated with recurrence (1.38; 1.12-1.69). The authors noted that exposures were self-reported, that some effect of smoking may remain, and that follow-up was short. They concluded that exposure history may affect prognosis.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Multicenter prospective cohort study (Be-Well Study)
• Who was studied: 1472 patients aged at least 21 with a first diagnosis of non-muscle-invasive bladder cancer (stage Ta, Tis or T1), recruited at Kaiser Permanente Northern and Southern California, 2015 to 2019
• Exposure: Self-reported lifetime environmental exposures (including asbestos, formaldehyde, chemicals, dusts, exhausts and others) and occupations, with frequency and duration. Individual exposures were grouped into 5 carcinogen groups, one of them asbestos. The article does not report asbestos fiber types or fiber-specific results.
• Main results:
  • 1076 of 1472 participants (73.1%) reported ever exposure to environmental and/or occupational risk factors
  • Over a median follow-up of 28 months, 473 (32.1%) recurrences occurred. Of these 473, 89 involved progression, and 65 of them were progression to muscle-invasive bladder cancer.
  • In the fully adjusted model, participants with any environmental or occupational exposure had higher risk of progression (HR 1.79; 95% CI 1.04-3.09) and of progression to muscle-invasive disease (HR 2.28; 95% CI 1.16-4.50). Their risk of recurrence was not higher.
  • After full adjustment, exposure to asbestos (OR 1.43; 95% CI 1.11-1.84) and to arsenic (OR 1.27; 95% CI 1.01-1.63) was associated with advanced stage (T1 or Tis rather than Ta) at diagnosis
  • For asbestos and advanced stage by duration of exposure: OR 1.46 (95% CI 1.04-2.05) for 5 years or less, 1.48 (1.00-2.16) for more than 5 to 20 years, and 1.39 (0.88-2.17) for more than 20 years
  • Only asbestos exposure lasting more than 5 years was associated with recurrence (HR 1.29; 95% CI 1.01-1.66)
  • Formaldehyde exposure was associated with recurrence (HR 1.38; 95% CI 1.12-1.69) but not with progression
  • More than 20 years of exposure to all environmental and occupational carcinogens was associated with higher odds of high-grade disease (OR 1.41; 95% CI 1.04-1.92)
• The authors' conclusion: The authors concluded that carcinogen exposure history may affect the prognosis of non-muscle-invasive bladder cancer. They suggested it could be added to current risk stratification systems.
• Limitations the authors state:
  • Residual effects of smoking cannot be ruled out
  • Exposures were self-reported and subject to recall bias
  • No detailed job or workplace data were collected, so exposure levels could not be assessed
  • Follow-up was short
  • There were few events, especially progression events, which made confidence intervals wide

Topics

Medical terms in this study, explained in our Lexicon: Occupational Exposure, Prognosis, Cohort Study, Hazard Ratio, Odds Ratio.

Related studies

• Use of job-exposure matrix in an occupational analysis of lung and bladder cancers on the basis of death certificates — D. Coggon, B. Pannett, et al. (1984)
• Bladder cancer invasion predictability based on preoperative neutrophil-lymphocyte ratio — M. Kaynar, M.E. Yıldırım, et al. (2014)
• Arsenic, tobacco smoke, and occupation: associations of multiple agents with lung and bladder cancer — C. Ferreccio, Y. Yuan, et al. (2013)
• Occupational cancer of the urinary bladder in dyestuffs operatives and of the lung in asbestos textile workers and iron-ore miners — G.M. Bonser, J.S. Faulds, et al. (1955)
• Occupational asbestos exposure and urinary bladder cancer: a systematic review and meta-analysis — N. Franco, A. Godono, et al. (2023)
• Occupational exposure to asbestos and urinary bladder cancer — R. Molinini, L. Paoletti, et al. (1992)

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