Androgen deprivation therapy, comorbidity, cancer stage and mortality from COVID-19 in men with prostate cancer

Abstract

Background

Androgens facilitate entrance of the severe acute respiratory syndrome coronavirus 2 into respiratory epithelial cells, and male sex is associated with a higher risk of death from corona virus disease (COVID-19). Androgen deprivation therapy (ADT) could possibly improve COVID-19 outcomes.

Methods

In a case–control study nested in the Prostate Cancer data Base Sweden (PCBaSe) RAPID 2019, we evaluated the association between ADT and COVID-19 as registered cause of death in men with prostate cancer. Each case was matched to 50 controls by region. We used conditional logistic regression to adjust for confounders and also evaluated potential impact of residual confounding.

Results

We identified 474 men who died from COVID-19 in March–December 2020. In crude analyses, ADT exposure was associated with an increased risk of COVID-19 death (odds ratio [OR] 5.05, 95% CI: 4.18–6.10); however, the OR was substantially attenuated after adjustment for age, comorbidity, prostate cancer characteristics at diagnosis, recent healthcare use, and indicators of advanced cancer (adjusted OR 1.25, 95% CI: 0.95–1.65). If adjustment has accounted for at least 85% of confounding, then the true effect could be no more than a 5% reduction of the odds for COVID-19 death.

Conclusions

The increased mortality from COVID-19 in men with prostate cancer treated with ADT was mainly related to high age, comorbidity, and more advanced prostate cancer. There was no evidence to support the hypothesis that ADT is associated with improved COVID-19 outcomes.

Keywords:

• COVID-19
• SARS-CoV-2
• androgen deprivation therapy
• GnRH agonists
• prostate cancer

Acknowledgements

This project was made possible by the continuous work of the National Prostate Cancer Register of Sweden (NPCR) steering group: Pär Stattin (chairman), Ingela Franck Lissbrant (co-chair), Camilla Thellenberg, Eva Johansson, Lennart Åström, Magnus Törnblom, Stefan Carlsson, Marie Hjälm Eriksson, David Robinson, Mats Andén, Ola Bratt, Jonas Hugosson, Maria Nyberg, Per Fransson, Fredrik Jäderling, Fredrik Sandin and Karin Hellström. We thank Susan Bromley, EpiMed Communications Ltd, Abingdon, Oxford, UK for editorial assistance funded by the University of Uppsala.

Consent to participate

The requirement for informed consent was waived by the Ethical Review Authority.

Disclosure statement

The public health-care administration for Region Uppsala in Sweden has, on behalf of the National Prostate Cancer Register, made agreements on subscriptions for quarterly reports from Patient-overview Prostate Cancer with Astellas, Sanofi, Janssen, and Bayer, as well as research projects with Astellas, Bayer, and Janssen. Johan Styrke is a co-PI of the Covidenza trial of Enzalutmide for Covid 19: ClinicalTrials.gov Identifier: NCT04475601. Johan Styrke report no financial interest in the present study or in the Covidenza trial. Stacy Loeb reports equity in Gilead. Region Uppsala has, on behalf of NPCR, made agreements on subscriptions for quarterly reports quarterly reports from Patient-overview Prostate Cancer with Astellas, Janssen, and Bayer, as well as research projects with Astellas, Bayer, and Janssen. All remaining authors have declared no conflicts of interest.

Data availability statement

Data used in the present study was extracted from the Prostate Cancer Database Sweden (PCBaSe), which is based on the National Prostate Cancer Register (NPCR) of Sweden and linkage to several national health-data registers. The data cannot be shared publicly because the individual-level data contain potentially identifying and sensitive patient information and cannot be published due to legislation and ethical approval (https://etikprovningsmyndigheten.se). Use of the data from national health-data registers is further restricted by the Swedish Board of Health and Welfare (https://www.socialstyrelsen.se/en/) and Statistics Sweden (https://www.scb.se/en/) which are Government Agencies providing access to the linked healthcare registers. The data will be shared on reasonable request in an application made to any of the steering groups of NPCR and PCBaSe. For detailed information, please see www.npcr.se/in-english, where registration forms, manuals, and annual reports from NPCR are available alongside a full list of publications from PCBaSe. The statistical program code used for the present study analyses can be provided on request (contact [email protected]).

Ethics approval

Approved by the Swedish Ethical Review Authority: Dnr 2020-03889.

Additional information

Funding

This work was supported by the Swedish Research Council (grant number 2020-05866). The funding source had no impact on the design, conduct, or interpretation of the study.