Perspectives

In this Perspective, current evidence to support de-escalation strategies of attenuated chemotherapy, radiotherapy and surgery for stage II seminoma to minimize the toxic effects of treatment is described and new potential de-escalation strategies are discussed.

Since its inception in 1922, prostate biopsy has undergone considerable changes in both technique and indication. In this Perspective, the authors describe the history of prostate biopsy and consider the role of imaging in prostate biopsy, now and in the future.

This Perspective covers existing patient-derived xenografts (PDXs) of prostate cancer, and their features and uses in basic and preclinical research. The authors also discuss the need for additional PDXs, and how collaboration in prostate cancer PDX research can be improved.

Combination treatment with androgen deprivation therapy plus chemotherapy or novel hormonal agents showed promising results for the treatment of patients with newly diagnosed metastatic prostate cancer. However, real-world data show a very low uptake of this therapy in clinical practice. In this Perspective, the authors discuss data and potential reasons behind this trend.

In this Perspective, the authors present clinical scenarios in which prostate hyperplasia and prostate cancer overlap, with a specific focus on holmium laser enucleation of the prostate (HoLEP). Variables associated with incidental prostate cancer detection at HoLEP and prostate cancer development after HoLEP, as well as the role of HoLEP in patients with biopsy-proven prostate cancer, are also discussed.

Adjuvant therapies in renal cell carcinoma (RCC) disrupt multiple steps of the metastatic cascade. Results from clinical trials to assess adjuvant treatment with immunotherapeutic agents in patients with resected clear cell RCC were promising, but the utility of tyrosine kinase inhibitors in this setting was not clearly shown. In this Perspective, the authors provide an overview of completed and ongoing clinical trials for adjuvant treatment of RCC, highlighting future directions and challenges in the field.

In this Perspective, the authors provide an overview of the roles of three genes, PBRM1, SETD2 and BAP1, which are commonly lost with chromosome 3p deletion in patients with clear cell renal cell carcinoma (ccRCC). The authors discuss the implication of these genes in cancer-related pathways and how an improved understanding of these mechanisms might help to develop potential new therapies in ccRCC.

Altered lipid metabolism is a visually obvious, distinguishing feature of clear-cell renal cell carcinoma. In this Perspective the authors describe the molecular mechanisms driving fatty acid accumulation and discuss potential therapeutic targets in this disease.

An association between infertility and poor somatic health exists, and infertility could be used as an indicator of a future pathological condition. However, the bidirectional relationship between infertility and poor health needs to be elucidated. In this Perspective, the authors discuss current advances and gaps in this area, focusing on lipid peroxidation and oxidative damage as potential molecular links between infertility and somatic health.

Lower urinary tract disorders (LUTDs) are common in the elderly, owing to age-related dysfunction of the lower urinary tract (LUT). An endogenous inhibitor of purine nucleoside phosphorylase, 8-aminoguanine, has been shown to reverse the effects of ageing on LUT biochemistry, structure and function, offering a novel potential treatment for LUTDs.

In this Perspective, the authors discuss the past, present and future of PSA screening for the early detection of aggressive prostate cancer and propose a way forward for the rational use of PSA testing as part of a risk-adapted screening strategy.

In this Review, the authors discuss racial differences in the prevalence of genetic mutations in the main molecular drivers of prostate cancer and provide input regarding the role of genomics in racial disparities observed in prostate cancer outcomes.

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.