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The deleterious association between proton pump inhibitors and prostate cancer-specific mortality – a population-based cohort study

Prostate Cancer and Prostatic Diseases volume 23, pages 622–629 (2020)Cite this article

Subjects

Abstract

Background

Proton pump inhibitors (PPIs) are commonly prescribed medications that have been shown to have contradicting effects on cancer. We aimed to investigate the effect of pantoprazole and other PPIs on prostate cancer (PCa) specific mortality (PCSM), use of androgen deprivation therapy (ADT), and PCa diagnosis using a large Canadian population-based cohort.

Methods

We identified 21,512 men aged ≥ 66, with a history of a single negative prostate biopsy and no previous use of any of the analyzed medications between 1994 and 2016. Multivariable Cox regression models with time-dependent covariates were used to assess the associations of PPIs with PCa outcomes. All models included other medications with a putative chemopreventative effect on PCa-outcomes, and were adjusted for age, rurality, comorbidity, and study inclusion year.

Results

Over a mean follow-up of 8.06 years (SD 5.44 years), 10,999 patients (51.1%) used a PPI, 5187 patients (24.1%) had PCa, 2043 patients (9.5%) were treated with ADT, and 805 patients (3.7%) died from PCa. For every 6 months of cumulative use, pantoprazole was associated with a 3.0% (95% CI 0.3–6.0%) increased rate of ADT use, while any use of other PPIs was associated with a 39.0% (95% CI 18.0–64.0%) increased risk of PCSM. No association was found with PCa diagnosis.

Conclusions

Upon validation of the potentially negative association of PPIs with PCa, PPI use may need to be reassessed in PCa patients.

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Fig. 1: Prostate cancer diagnosis, treatment and mortality rates.

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Acknowledgements

This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). The opinions, results and conclusions reported in this paper are those of the authors and are independent from the funding source. No endorsement by ICES of the Ontario MOHLTC is intended or should be inferred. The datasets used in this study were linked using unique encoded identifiers and analyzed at ICES. Parts of this material are based on data and information compiled and provided by CIHI. However, the analyses, conclusions, opinions and statements expressed herein are those of the author, and not necessarily those of CIHI. Parts of this material are based on data and information provided by Cancer Care Ontario (CCO). The opinions, results, view, and conclusions reported in this paper are those of the authors and do not necessarily reflect those of CCO. No endorsement by CCO is intended or should be inferred. We thank IMS Brogan Inc. for use of their Drug Information Database.

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Authors and Affiliations

  1. Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, ON, Canada

    Hanan Goldberg, Girish S. Kulkarni, Miran Kenk, Christopher J. D. Wallis & Neil Fleshner

  2. Institute of Medical Science, University of Toronto, Toronto, ON, Canada

    Hanan Goldberg, Shabbir M. H. Alibhai & Neil Fleshner

  3. Department of Urology, SUNY Upstate Medical University, Syracuse, NY, USA

    Hanan Goldberg

  4. Institute for Clinical Evaluative Sciences, Toronto, ON, Canada

    Hanan Goldberg, Refik Saskin & Girish S. Kulkarni

  5. Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada

    Faizan K. Mohsin & Olli Saarela

  6. Department of Radiation Oncology, University of Toronto; and Techna Institute, University Health Network, Toronto, ON, Canada

    Alejandro Berlin

  7. Department of Urology, Vanderbilt University Medical Center, Nashville, TN, USA

    Christopher J. D. Wallis

  8. Department of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA

    Thenappan Chandrasekar

  9. Division of Urology, Department of Surgery, Medical College of Georgia, Augusta University, Augusta, GA, USA

    Zachary Klaassen

  10. Georgia Cancer Center, Augusta, GA, USA

    Zachary Klaassen

  11. Department of Medical Biophysics, University of Toronto, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada

    Linda Penn

  12. Department of Medicine, University Health Network and University of Toronto, Toronto, ON, Canada

    Shabbir M. H. Alibhai

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Contributions

Design and conception: HG, NF, SA, GSK, RS. Data collection and analyses: HG, FKM, OS, RS, AB, SH, CJDW, LP, GSK, NF. Writing of manuscript: HG, FKM. Editing and reviewing of manuscript: FKM, AB, SA, RS, CJDW, ZK, TC, AEA, RKS, OS, LP, GB, GSK, NF.

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Correspondence to Hanan Goldberg.

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Goldberg, H., Mohsin, F.K., Saskin, R. et al. The deleterious association between proton pump inhibitors and prostate cancer-specific mortality – a population-based cohort study. Prostate Cancer Prostatic Dis 23, 622–629 (2020). https://doi.org/10.1038/s41391-020-0248-9

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