Perspectives

In this Perspective, the authors discuss the complex links among inflammation, dysbiosis, ageing and cancer, examining data that suggest that ageing and inflammation can promote bladder cancer development, how ageing might lead to or promote dysbiosis, and how dysbiosis could influence treatment response.

The sixth edition of the WHO (World Health Organization) semen analysis manual has been released 10 years after the previous edition and includes important updates. In this Perspective article, a comprehensive overview and discussion of the newly released WHO manual are provided. Limitations of routine semen analysis-based infertility assessment and potential solutions to improve male infertility work-up are also discussed.

Since calcium/calmodulin-dependent kinase kinase 2 (CAMKK2) was identified as an androgen-receptor-regulated gene, important functional roles of CAMKK2 in prostate cancer progression have been shown in preclinical models. In this Perspective, the authors present evidence supporting an oncogenic role of CAMKK2, and also discuss mechanisms of regulation and emerging non-cell-autonomous roles of CAMKK2. Moreover, the potential use of CAMKK2 as a biomarker and/or therapeutic target in prostate cancer is discussed.

Several therapeutic options for the treatment of renal cell carcinoma (RCC) are available, but challenges in the field such as drug resistance still exist. In this Perspective, Sager et. al discuss the role and the inhibition of the cyclin-dependent kinases CDK4 and CDK6 in RCC. The role of CDK4/6 at the interface between metabolic signalling pathways and cell cycle, the wide use of CDK4/6 inhibitors in cancer treatment, and promising preclinical studies testing these drugs in RCC support further investigation of CDK4/6 targeting in RCC.

In this Perspective, the authors describe our current knowledge of the involvement of galectins in sexually transmitted infections in the female genital tract. They also discuss unresolved questions in this emerging field and highlight novel opportunities to reduce transmission and dissemination of sexually transmitted pathogens using galectin-targeted agents.

In this Perspective, Tasoglu describes toilet-based continuous health monitoring using urine, reviewing currently available smart toilets and discussing the development and implementation of devices and methods that will shift the focus of medicine to the well-being of humans.

Penile cancer is a growing health-care concern worldwide. Despite its rarity, penile cancer has a disproportionate impact on some countries, as the location with the highest incidences are invariably those with low resources and few registries or trials. In this Perspective, the authors discuss how global collaboration and centralization of care can help to improve management of penile cancer worldwide, but especially in areas where resources are limited.

Early studies in patients and animal models have suggested that SARS-CoV-2 can access the reproductive system and could have effects on fertility. In this Perspective, Edenfield and Easley present the evidence for mechanisms of infection of reproductive cells by SARS-CoV-2 and consider the potential for testicular dysfunction in patients who have had COVID-19.

COVID-19 has been shown to be associated with a higher mortality rate in men than in women. In this Perspectives article, the authors posit that this disparity is due to a failure to invest in men’s health and discuss the biological, social and economic factors that have contributed to the sex disparities in mortality from COVID-19, as well as considering how a streamlined men’s health programme with the urologist in a central role could address these issues.

The prostate is divided into the peripheral, transition and central zones, which have different prostate cancer incidences and prognoses. Differences between the zones suggest their potential roles in tumour aggressiveness, but treatment of prostate cancer remains zonal agnostic. Improved understanding of the zones and their roles in tumorigenesis could improve prostate cancer management.

Trials evaluating novel therapies in the neoadjuvant setting must have clearly defined study elements and appropriately selected end points to ensure the applicability of the trial and enable interpretation of the study results. In this Perspectives, the authors describe the findings of a public workshop jointly sponsored by the US Food and Drug Administration and the Bladder Cancer Advocacy Network, which discussed key elements and end points when designing trials of neoadjuvant therapy for muscle-invasive bladder cancer.

Society guidelines recommend incorporating palliative care into standard oncological care. However, misconceptions regarding palliative care are common — notably, palliative care and treatments seeking to cure or prolong life are not mutually exclusive. In this article, the authors discuss the integration of palliative care into surgical urologic oncology and consider palliative care guidelines, indications for palliative care use, and how the field of urologic oncology can adopt best practices.

Bacillus Calmette–Guérin (BCG) has been used to prevent tuberculosis for a century and is also a standard approach for the treatment of non-muscle-invasive bladder cancer. However, BCG also has a plethora of non-specific effects that occur via the induction of trained immunity and have raised the hypothesis that BCG vaccination could be used to protect against coronavirus disease 2019 (COVID-19). In this Perspective, the authors describe the history of BCG, discuss the mechanisms of its effects, and consider its potential role during the COVID-19 pandemic.

Premature ejaculation is thought to affect up to one-third of men, but a considerable proportion of patients do not meet the diagnostic criteria and do not, therefore, receive treatment for their symptoms. In this Perspectives article, the authors propose a new taxonomy for premature ejaculation, to encompass the subclinical disorder and its co-occurrence with erectile dysfunction, with a view to improving patient management.

In this Perspective, Connor et al. examine the current status of autonomous technologies in robotic-assisted surgery in urology and discuss the future role of the urological surgeon in an era of increasing use of automation and artificial intelligence.

Renal cell carcinoma (RCC) incidence is increasing worldwide. Here, the authors consider the potential benefits and harms of screening for RCC and discuss whether enough evidence is available to begin a clinical trial of RCC screening.

Here, the authors describe the characteristics of an ideal screening test for prostate cancer and examine why PSA fails to meet these attributes. They discuss whether an abbreviated MRI protocol could be an alternative or additional screening test for prostate cancer and explore its inherent challenges and potential solutions.

The precise mechanism of action by which BCG acts in bladder cancer therapy is unclear. BCG induces a non-specific enhancement of the biological function of innate immune cells, creating an immunological memory known as trained immunity. In this Perspective, the authors propose that trained immunity could be an important mechanism mediating BCG immunotherapy and could contribute to a personalized approach to BCG therapy in patients with bladder cancer.

Prostate Cancer Diagnosis and Treatment Enhancement Through the Power of Big Data in Europe (PIONEER) is a European network of excellence for big data in prostate cancer, consisting of 32 private and public stakeholders from 9 countries across Europe. In this Perspectives article, the authors introduce the PIONEER project and describe its aims and plans for ultimately improving prostate cancer care through the use of big data.

In this Perspectives, a pioneer in the field of robotic radical prostatectomy describes the history of the technique and changing indications for its use, from an operation once considered useless, to one offered to almost all patients with low-risk disease, to a procedure that now has a role in advanced disease as part of a multimodal approach.