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Role of urinary tract infection in bladder cancer: a systematic review and meta-analysis

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World Journal of Urology Aims and scope Submit manuscript

Abstract

Purpose

We sought to examine the literature reporting the effect of urinary tract infection (UTI) on non-schistosomiasis-related UBC (UBCNS) through a systematic review and meta-analysis.

Methods

A predefined study protocol was developed according to PRISMA. Medline and Scopus were searched for all studies investigating exposure to UTI with UBCNS as the primary outcome. Potential studies were screened against eligibility criteria. Clinical heterogeneity was assessed and groups with more than two studies were evaluated by random effect meta-analysis. Study-level bias was assessed with the Newcastle–Ottawa Scale (NOS). In cases of substantial between study heterogeneity (I2 > 50%), predefined sensitivity and subgroup analyses were performed.

Results

Of 16 eligible studies, eight case–control studies spanning four decades and five countries were suitable for quantitative analysis. Main analysis favored exposure to UTI increasing risk of subsequent UBCNS (RR 1.33 [95% CI 1.14–1.55]). This effect was no longer statistically significant after excluding studies published prior to year 2000 and at high risk of bias. Between study heterogeneity was considerable for nearly all analyses and not reduced by predefined sensitivity or subgroup analyses.

Conclusion

Exposure to UTI favors increased risk for UBCNS, particularly in men, but these effects were statistically insignificant when pooling data from the most recent and highest quality studies. These data do not support findings of previously published studies, that report on heterogenous populations with poor definitions of UTI and minimal control for important confounders. Results from previous studies should be viewed as hypothesis generating. This review highlights the need for higher quality investigation.

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Abbreviations

CI:

Confidence interval

HR:

Hazard ratio

NOS:

Newcastle–Ottawa Scale

OR:

Odds ratio

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

PROSPERO:

International Prospective Register of Systematic Reviews

RR:

Risk ratio

SCC:

Squamous cell carcinoma

UBC:

Urinary bladder cancer

UBCNS :

Non-schistosomiasis-related UBC

UC:

Urothelial carcinoma

UTI:

Urinary tract infection

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Acknowledgements

We thank the anonymous reviewers for their role in improving our manuscript.

Funding

CEB is supported by the Joseph E. Robert, Jr. Fellowship at the Sheikh Zayed Institute for Pediatric Surgical Innovation, part of the Children’s National Health System. MHH is supported by a National Institutes of Health R56 (AI119168) grant.

Author information

Authors and Affiliations

  1. Division of Pediatric Urology, Children’s National Health System, 111 Michigan Ave, NW, Washington, DC, 20010, USA

    Christopher E. Bayne & Michael H. Hsieh

  2. School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA

    Dannah Farah

  3. Department of Research/Division of Urology and Nephrology, Connecticut Children’s Medical Center, Hartford, CT, USA

    Katherine W. Herbst

  4. Biomedical Research Institute, Rockville, MD, USA

    Michael H. Hsieh

  5. Departments of Urology and Pediatrics, The George Washington University, Washington, DC, USA

    Michael H. Hsieh

Authors
  1. Christopher E. Bayne
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  2. Dannah Farah
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  3. Katherine W. Herbst
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  4. Michael H. Hsieh
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Contributions

CEB: Protocol/project development, data collection, data analysis, manuscript writing. DF: Protocol/project development, data collection. KWH: Data analysis. MHH: Protocol/project development.

Corresponding author

Correspondence to Christopher E. Bayne.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

For this type of study formal consent is not required.

Research involving human participants and/or animals

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with human participants or animals performed by any of the authors.

Protocol registration

This study protocol (2016:CRD42016053888) was developed prior to data collection according to PRISMA and PRISMA-P guidelines and registered with the International Prospective Register of Systematic Reviews (PROSPERO): http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42016053888.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (TIFF 75 kb) Flow diagram of study selection

345_2018_2257_MOESM2_ESM.png

Supplementary material 2 (PNG 4 kb) Funnel plot illustrating risk ratio according to standard errorLegend: RR, risk ratio; SE, standard error; dashed line = overall effect; RR of 1 equates to no intervention effect

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Supplementary material 3 (TIFF 83 kb) Pooled analysis for exposure to UTI on risk of UBC according to sex. A) Males only. B) Females only

345_2018_2257_MOESM4_ESM.tif

Supplementary material 4 (TIFF 55 kb) Pooled analysis exposure to UTI on UBC risk according to smoking history*. A) With smoking history. B) Without smoking history. *Jiang et al data reported smoking data for women only and excluded data within 5 years of cancer diagnosis

345_2018_2257_MOESM5_ESM.tif

Supplementary material 5 (TIFF 63 kb) Pooled analysis for exposure to multiple UTI (versus no exposure) on risk of UBC*. A) Overall analysis. B) Analysis after excluding studies prior to year 2000 and with high risk of bias. * Jhamb et al excluded data within 3 years of cancer diagnosis; Jiang et al reported episodes of bladder infection for women only and excluded data within 5 years of cancer diagnosis

Supplementary material 6 (DOCX 13 kb)

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Bayne, C.E., Farah, D., Herbst, K.W. et al. Role of urinary tract infection in bladder cancer: a systematic review and meta-analysis. World J Urol 36, 1181–1190 (2018). https://doi.org/10.1007/s00345-018-2257-z

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  • DOI: https://doi.org/10.1007/s00345-018-2257-z

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