ASCO GU 2020: The Deleterious Association Between Proton Pump Inhibitors and Prostate Cancer Specific Death

San Francisco, California ( Proton pump inhibitors (PPIs) are a commonly prescribed class of medications. Although in-vitro and in-vivo data have shown PPIs to have anti-tumor effects, more recent studies suggest an increased cancer risk in several solid organs, including an association with increased risk of gastric, colorectal, pancreatic, and prostate cancer. Pantoprazole, a commonly prescribed PPI, has been shown to harbor a protective effect in human prostate cancer cells. Presented during the Prostate Cancer Session at the 2020 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), Hanan Goldberg, MD reported results assessing the effect of pantoprazole and other PPIs on prostate cancer-specific death and additional prostate cancer outcomes.

This study was a retrospective, population-based cohort study of data incorporated from the Institute for Clinical and Evaluative Sciences in Ontario, Canada to identify all men aged 66 and above with a history of a single negative prostate biopsy between 1994 and 2016. In Ontario, medication prescriptions are freely available to everyone 65 years and older through the Ontario Drug Benefit program, allowing accurate capture of all provided prescriptions in this population. The authors used multivariable Cox regression models with time-dependent covariates, to assess the effect of PPIs on prostate cancer diagnosis, androgen deprivation therapy (ADT) use, and prostate cancer-specific death. All models included other medications with a putative effect on prostate cancer. All models were adjusted for age, rurality, comorbidity, and year of patient study inclusion.

This study included 21,512 men with a mean follow-up time of 8.06 years (SD 5.44 years). A total of 10,999 patients (51.1%) used a PPI during the study period with 4,377 patients using pantoprazole and 6,622 patients using other PPIs. A total of 5,187 patients (24.1%) were diagnosed with prostate cancer, 2,043 patients (9.5%) were treated with ADT, and 805 patients (3.7%) died from prostate cancer. Pantoprazole was associated with a 3.0% (95% confidence interval [CI] 0.3%-6,0%) increased rate of being treated with ADT for every six months of cumulative use, while any use of all other PPIs was associated with a 39.0% (95% CI 18.0%-64.0%; hazard ratio [HR] 1.39, 95% CI 1.18-1.64) increased prostate cancer-specific mortality. No significant association was found with a prostate cancer diagnosis. The following graph depicts the percentage of prostate cancer diagnosis, any use of ADT, and prostate cancer-specific death, stratified by age:

the percentage of prostate cancer diagnosis

Dr. Goldberg acknowledged several limitations of this study, including (i) this study being a retrospective population-based analysis with its inherent selection bias and health administrative database associated inaccuracies, (ii) the data being limited to men older than 66, and containing 20-year old data, (iii) lacking information regarding ethnicity, disease stage and grade, pertinent family history, and personal genetic risk, (iv) the risk of unaccounted residual confounding.

Dr. Goldberg concluded this epidemiological study assessing PPI and association with prostate cancer outcomes with the following conclusions:

  • In prostate cancer patients, use of PPIs was associated with increased prostate cancer-specific mortality (PCSM)
  • The reported potential long-term impact of these medications on prostate cancer outcomes need to be confirmed in additional studies
  • If these findings are validated, the broad use of PPIs in prostate cancer patients may need to be reconsidered

Presented by: Hanan Goldberg, MD, Urology Department, SUNY Upstate Medical University, Syracuse, New York, New York

Co-Authors: Faizan Moshin, Refik Saskin, Girish S. Kulkarni, Alejandro Berlin, Miran Kenk, Christopher J.D. Wallis, Thenappan Chandrasekar, Zachary Klaassen, Olli Saarela, Linda Penn, Shabbir M.H. Alibhai, Neil Eric Fleshner; Department of Urology, SUNY Upstate, Syracuse, NY; Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada; Institute for Clinical Evaluative Sciences, Toronto, ON, Canada; Division of Urology, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, ON, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Division of Urology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada; Department of Urology, Thomas Jefferson University, Philadelphia, PA; Division of Urology, Medical College of Georgia at Augusta University, Georgia Cancer Center, Augusta, GA; University of Toronto, Toronto, ON, Canada; Princess Margaret Cancer Centre, Toronto, ON, Canada; Princess Margaret Hospital, University Health Network, Toronto, ON, Canada; Division of Urologic Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada

Written by: Zachary Klaassen, MD, MSc, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Twitter: @zklaassen_md at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California

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