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Men whose prostate cancer was treated with androgen-deprivation therapy (ADT) had a significantly lower risk of COVID-19 infection, a large retrospective study of Italian patients showed.

Only four of 5,273 men treated with ADT tested positive for the novel coronavirus, one had severe disease, and none of them died. That compared with 114 COVID-19 cases among 37,161 men with prostate cancer but no ADT, 31 instances of severe disease, and 18 deaths.

The absolute numbers translated into a fourfold lower risk of COVID-19 infection for prostate cancer patients treated with ADT and similar odds for developing severe disease. The results suggest the possibility that ADT could have potential for COVID-19 treatment or prevention, Andrea Alimonti, MD, of the Universita della Svizzera Italiana in Bellinzona, Switzerland, and co-authors reported in .

"These data need to be further validated in additional large cohorts of SARS-CoV-2-infected patients and corrected for multiple variables," the authors stated in their conclusion. "ADT, based on luteinizing hormone-releasing hormone agonist/antagonists or AR [androgen receptor] inhibitors, may be considered to reduce SARS-CoV-2 infections or complications in high-risk male populations. Given that the effects of these compounds are reversible, they could be used transiently ... in patients affected by SARS-CoV-2, thereby reducing the risk of side effects due to long-term administration."

The study will likely provide fodder for a scientific discussion of ADT's therapeutic or prophylactic potential in COVID-19 -- especially since another study scheduled to be published in the Journal of Urology came to different findings and conclusions, said Eric Klein, MD, of the Cleveland Clinic.

"It's an interesting question, but I think the answer is unclear at present," Klein told 番茄社区app by email.

The study by Alimonti and colleagues had its genesis in the recognition that cell entry by the novel coronavirus requires priming by TMPRSS2, a transmembrane serine protease implicated in the spread of several clinically relevant viruses, including SARS and MERS coronaviruses.

Recent COVID-19 research suggested that after the virus gains entry into a cell, TMPRSS2 helps facilitate the fusion of viral and cellular membranes, the authors stated. In vitro studies indicate that may help prevent COVID-19 infection.

TMPRSS2 is highly expressed in prostate cancer, and its transcription is regulated by the androgen receptor, Alimonti and co-authors continued. Preclinical studies have shown that androgen administration induces TMPRSS2 expression in human lung epithelial cells and that androgen deprivation reduces TMPRSS2 transcription in mouse lung tissue.

With that background information, the authors hypothesized that ADT "may protect patients affected by prostate cancer from SARS-CoV-2 infections."

To pursue the hypothesis, the investigators relied on data from a registry of patients who tested positive for COVID-19 in the Veneto region of Italy, a tumor registry, and a pharmacy database. The team identified 9,280 patients (4,532 men) with laboratory-confirmed infection at 68 hospitals. Male patients included 430 men (9.5%) with cancer, 118 (2.6%) with prostate cancer.

Overall, men with cancer had more severe disease, as 47.0 of all men with COVID-19 required hospitalization and 6.9% died, compared with a hospitalization rate of 67.9% and mortality of 17.4% in the subgroup of men with cancer.

Age did not account for the differences in hospitalization and mortality, the authors noted. The findings were consistent with those of showing higher rates of COVID-19 infection and more severe disease among men with cancer.

The data included a total of 42,434 men with prostate cancer in the Veneto region. Of those, 5,273 received ADT and four (0.08%) developed laboratory-confirmed COVID-19. The remaining 37,161 patients did not receive ADT, and 114 (0.3%) developed COVID-19. The difference translated to an odds ratio for infection of 4.05 for men who were not treated with ADT (95% CI 1.55-10.59, P=0.0043).

One of the four ADT-treated patients who developed COVID-19 had severe disease, requiring a stay in an intensive care unit (ICU). In contrast, 31 patients without ADT treatment had severe disease, 18 of whom died and 13 requiring ICU care. Patients who did not receive ADT were more than four times as likely to have severe disease (OR 4.40, 95% CI 0.76-25.50, P=0.0982).

Despite finding the data interesting, Klein expressed reservations about a key component of the biological rationale set forth by Alimonti and colleagues.

"TRMPSS2 is probably not under androgen regulation in the lung, so it's not clear how ADT would affect its expression," he said.

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