Two Novel Ceramide-Like Molecules and miR-5100 Levels as Biomarkers Improve Prediction of Prostate Cancer in Gray-Zone PSA

Reliable liquid biopsy-based tools able to accurately discriminate prostate cancer (PCa) from benign prostatic hyperplasia (BPH), when PSA is within the “gray zone” (PSA 4–10), are still urgent. We analyzed plasma samples from a cohort of 102 consecutively recruited patients with PSA levels between 4 and 16 ng/ml, using the SANIST-Cloud Ion Mobility Metabolomic Mass Spectrometry platform, combined with the analysis of a panel of circulating microRNAs (miR). By coupling CIMS ion mobility technology with SANIST, we were able to reveal three new structures among the most differentially expressed metabolites in PCa vs. BPH. In particular, two were classified as polyunsaturated ceramide ester-like and one as polysaturated glycerol ester-like. Penalized logistic regression was applied to build a model to predict PCa, using six circulating miR, seven circulating metabolites, and demographic/clinical variables, as covariates. Four circulating metabolites, miR-5100, and age were selected by the model, and the corresponding prediction score gave an AUC of 0.76 (C.I. = 0.66–0.85). At a specified cut-off, no high-risk tumor was misclassified, and 22 out of 53 BPH were correctly identified, reducing by 40% the false positives of PSA. We developed and applied a novel, minimally invasive, liquid biopsy-based powerful tool to characterize novel metabolites and identified new potential non-invasive biomarkers to better predict PCa, when PSA is uninformative as a tool for precision medicine in genitourinary cancers.

Immunotherapies in Genitourinary Oncology: Where Are We Now? Where Are We Going?

For decades, limited options existed to treat metastatic genitourinary cancers, including treatment options that could be classified as immunotherapy. Historically, immunotherapy centered on systemic cytokines for the treatment of metastatic kidney cancer, which had several adverse effects, as well as the Bacillus Calmette–Guérin vaccine for non-metastatic bladder cancer. Within the past decade, advances in immunotherapy have led to several approvals from the United States Food and Drug Administration, particularly in the field of immune checkpoint inhibition. Immune checkpoint inhibitors (ICIs) are now being used extensively to treat multiple solid tumors, including kidney and bladder cancers, and they are also being tested in many other cancers. Despite encouraging data from phase 2/3 clinical trials, less is known about biomarkers that may predict better response to ICIs. The effect of ICIs in genitourinary cancers is heterogeneous, with some tumor types having little clinical data available, or ICIs having limited activity in other tumors. In this review, we briefly discuss approved immunotherapy agents prior to the time of ICIs. Then, given the emergence of this class of agents, we summarize the several important ICIs and the clinical trials that led to their approval. Finally, we mention ongoing and future clinical trials.

Oral microbiota in the oral-genitourinary axis: identifying periodontitis as a potential risk of genitourinary cancers

Periodontitis has been proposed as a novel risk factor of genitourinary cancers: although periodontitis and genitourinary cancers are two totally distinct types of disorders, epidemiological and clinical studies, have established associations between them. Dysbiosis of oral microbiota has already been established as a major factor contributing to periodontitis. Recent emerging epidemiological evidence and the detection of oral microbiota in genitourinary organs indicate the presence of an oral-genitourinary axis and oral microbiota may be involved in the pathogenesis of genitourinary cancers. Therefore, oral microbiota provides the bridge between periodontitis and genitourinary cancers. We have carried out this narrative review which summarizes epidemiological studies exploring the association between periodontitis and genitourinary cancers. We have also highlighted the current evidence demonstrating the capacity of oral microbiota to regulate almost all hallmarks of cancer, and proposed the potential mechanisms of oral microbiota in the development of genitourinary cancers.

The Evolving Clinical Management of Genitourinary Cancers Amid the COVID-19 Pandemic

Coronavirus disease–2019 (COVID-19), a disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, has become an unprecedented global health emergency, with fatal outcomes among adults of all ages throughout the world. There is a high incidence of infection and mortality among cancer patients with evidence to support that patients diagnosed with cancer and SARS-CoV-2 have an increased likelihood of a poor outcome. Clinically relevant changes imposed as a result of the pandemic, are either primary, due to changes in timing or therapeutic modality; or secondary, due to altered cooperative effects on disease progression or therapeutic outcomes. However, studies on the clinical management of patients with genitourinary cancers during the COVID-19 pandemic are limited and do little to differentiate primary or secondary impacts of COVID-19. Here, we provide a review of the epidemiology and biological consequences of SARS-CoV-2 infection in GU cancer patients as well as the impact of COVID-19 on the diagnosis and management of these patients, and the use and development of novel and innovative diagnostic tests, therapies, and technology. This article also discusses the biomedical advances to control the virus and evolving challenges in the management of prostate, bladder, kidney, testicular, and penile cancers at all stages of the patient journey during the first year of the COVID-19 pandemic.