The alternative renin-angiotensin-system (RAS) signalling pathway in prostate cancer and its link to the current COVID-19 pandemic.

BACKGROUND: The renin-angiotensin system is known to maintain blood pressure and body fluids. However, it has been found to consist of at least two major constituents, the classic and the alternative pathway, balancing and supporting each other's signalling in a very intricate way. Current research has shown that the renin-angiotensin system is involved in a broad range of biological processes and diseases, such as cancer and infectious diseases. METHODS AND RESULTS: We conducted a literature review on the interaction of the renin-angiotensin system and prostate cancer and explored the research on the possible impact of the SARS-CoV-2 virus in this context. This review provides an update on contemporary knowledge into the alternative renin-angiotensin system, its role in cancer, specifically prostate cancer, and the implications of the current COVID-19 pandemic on cancer and cancer care. CONCLUSION: In this work, we aim to demonstrate how shifting the RAS signalling pathway from the classic to the alternative axis seems to be a viable option in supporting treatment of specific cancers and at the same time demonstrating beneficial properties in supportive care. It however seems to be the case that the infection with SARS-CoV-2 and subsequent impairment of the renin-angiotensin-system could exhibit serious deleterious long-term effects even in oncology.

A phase III, randomized, open-label study (CONTACT-02) of cabozantinib plus atezolizumab versus second novel hormone therapy in patients with metastatic castration-resistant prostate cancer.

Cabozantinib inhibits multiple receptor tyrosine kinases, including the TAM kinase family, and may enhance response to immune checkpoint inhibitors. One cohort of the ongoing phase Ib COSMIC-021 study (NCT03170960) evaluating cabozantinib plus the PD-L1 inhibitor atezolizumab in men with metastatic castration-resistant prostate cancer (mCRPC) that has progressed in soft tissue on/after enzalutamide and/or abiraterone treatment for metastatic disease has shown promising efficacy. Here, we describe the rationale and design of a phase III trial of cabozantinib plus atezolizumab versus a second novel hormone therapy (NHT) in patients who have previously received an NHT for mCRPC, metastatic castration-sensitive PC or nonmetastatic CRPC and have measurable visceral disease and/or extrapelvic adenopathy - a population with a significant unmet need for treatment options. Trial Registration Clinical Trial Registration: NCT04446117 (ClinicalTrials.gov) Registered on 24 June 2020.

Impact of COVID-19 crisis on medical care of patients with metastasized uro-oncologic disease under systemic cancer therapy: a multicenter study in German university hospitals.

PURPOSE: To date, over 4.2 million Germans and over 235 million people worldwide have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Uro-oncology (UO) patients are particularly vulnerable but in urgent need of life-saving systemic treatments. Our multicentric study examined the impact of the COVID-19 crisis on the medical care of UO patients in German university hospitals receiving ongoing systemic anti-cancer treatment and to detect the delay of medical care, defined as deferred medical treatment or deviation of the pre-defined follow-up assessment. METHODS: Data of 162 UO patients with metastatic disease undergoing systemic cancer treatment at five university hospitals in Germany were included in our analyses. The focus of interest was any delay or change in treatment between February 2020 and May 2020 (first wave of the COVID-19 crisis in Germany). Statistical analysis of contingency tables were performed using Pearson's chi-squared and Fisher's exact tests, respectively. Effect size was determined using Cramér's V (V). RESULTS: Twenty-four of the 162 patients (14.8%) experienced a delay in systemic treatment of more than 2 weeks. Most of these received immuno-oncologic (IO) treatments (13/24, 54.2%, p = 0.746). Blood tests were delayed or canceled significantly more often in IO patients but with a small effect size (21.1%, p = 0.042, V = 0.230). Treatment of patients with renal cell carcinoma (12/73, 16.4%) and urothelial carcinoma (7/32, 21.9%) was affected the most. CONCLUSIONS: Our data show that the COVID-19 pandemic impacted the medical care of UO patients, but deferment remained modest. There was a tendency towards delays in IO and ADT treatments in particular.