Review Articles in 2020

This Review summarizes the manifestations of inter-tumoural and intra-tumoural heterogeneity in primary and metastatic prostate cancer, emphasizing the contribution of genomics studies and discussing the importance of phenotypic changes. The authors also critically discuss the implications for clinical management and research.

New and more effective treatments are urgently needed for bladder cancer. This Review discusses the role of nectin-4 as a therapeutic target for enfortumab vedotin (an antibody–drug conjugate) in locally advanced and metastatic urothelial carcinoma and outlines related clinical data.

Many aspects of human male reproduction can be modulated by cannabinoids and endocannabinoids (eCBs). Preclinical studies have shown that the endocannabinoid system (ECS) is involved in negative modulation of testosterone secretion, but the effect of in vivo exposure to cannabinoids on spermatogenesis remains a matter of debate. An improved understanding of the complex crosstalk between cannabinoids and eCBs might enable targeting of the ECS for modulation of human fertility.

Mammalian sperm must respond to a variety of cues, and dynamic regulation of ion signalling is, therefore, essential for sperm cells to adapt to their environment. In this Review, the authors describe the ion channels and membrane receptors controlling sperm activity, in particular the principal Ca²⁺-selective plasma membrane ion channel CatSper, and consider how sperm ion channels and membrane receptors are attractive targets for therapeutics and how these signalling processes might have implications for assisted reproductive technologies.

In this Review, van de Merbel et al. provide a comprehensive overview of the current patient-derived tumour models in use for urological cancers and discuss their advantages and limitations, as well as their potential for personalized treatment.

Radical prostatectomy is increasingly used as a first-line treatment for patients with high-risk, localized prostate cancer. Here, Wilkins and colleagues highlight the heterogeneous outcomes of these men and discuss the role of this approach in individualized, multimodal prostate cancer therapy.

Animal models that naturally and spontaneously form uroliths — including domestic dogs and cats, and a variety of other captive and wild species, such as otters, dolphins and ferrets — are an underused resource in the study of human stone disease and offer many potential opportunities for improving insight into stone pathogenesis. Improved collaboration between urologists, basic scientists and veterinarians is warranted to further our understanding of how stones form and to consider possible new preventive and therapeutic treatment options.

In this Review, Blum et al. summarize the current knowledge on sarcomatoid renal cell carcinoma, a diagnosis characterized by the presence of sarcomatoid dedifferentiation and a poor prognosis. They discuss the origin, presentation, molecular biology and treatment of this disease.

This Review summarizes current knowledge of the main gene fusions in genitourinary malignancies, discusses their growing importance in the understanding of the biology of tumours, and highlights their potential use as targets for precision medicine approaches.

For transgender people who experience gender dysphoria as children, in whom impending puberty is unacceptable for their psychosocial health and wellness, pubertal blockade is a therapeutic option. In this Review, the authors discuss pubertal blockade and its implications for fertility preservation, surgical care and psychosocial health, all of which must be considered and discussed with the patient and their family and/or legal guardian before initiation.

Complicated UTI (cUTI) incidence and the prevalence of antibiotic resistance among uropathogens are increasing. Here, the authors discuss different cUTI classification systems, describe current understanding of the aetiology of cUTIs and outline clinical studies of novel antibiotics in patients with cUTIs or pyelonephritis and the use of UTI as a model for other infection types in clinical studies.

In this Review, Aydin et al. discuss our current knowledge of the genomic, molecular and immunological make-up of penile squamous cell carcinoma and the findings of research studies to explore future therapeutic approaches in this disease.

Sharpley et al. describe the prevalence and effects of depression in men with prostate cancer and explore the causes and factors contributing to depression. They discuss depression definitions applicable to this patient population, how depression can be identified in the clinical setting and treatment considerations.

Lacerda Mariano and Ingersoll discuss how bacterial urinary tract infection affects the bladder, focusing on the development of immune responses and the cells and pathways that mediate immunity. They also highlight therapeutic approaches to bladder infection that are currently under development.

In this Review, Jackson and colleagues discuss the critical role of the urothelium in both normal urinary tract development and in congenital abnormalities of the urinary tract. Urothelial remodelling in congenital obstructive uropathy is also discussed.

In this Review, Perera et al. explain the concept and schedule protocols of intermittent androgen deprivation therapy (ADT) for patients with prostate cancer and discuss current evidence on safety, feasibility and benefits of intermittent ADT compared with continuous ADT.

The introduction of dedicated diagnostic guidelines for compulsive sexual behaviour disorder in the ICD-11 provides an opportunity to improve diagnosis and research into the disorder’s aetiology, assessment and therapy. For patients who consider their sexual behaviour uncontrollable, the interplay between excitatory and inhibitory factors could be in dysbalance. In this Review, Briken describes the aetiology and background of this often misunderstood disorder and provides a comprehensive approach to diagnosis and treatment.

Postoperative sexual function is most often unchanged or improved after treatment of pelvic organ prolapse. Nevertheless, some women experience sexual disorders and/or de novo dyspareunia after repair. Patient counselling is emerging as an important step before surgical prolapse repair.

Kidney stone disease is common and can be associated with alterations in urinary solute composition. Here, the authors outline general approaches for stone prevention, describe current understanding of the genetic influences underlying kidney stone formation and discuss the implications of a correct diagnosis for the clinical management of recurrent stone formers.

Radiotherapy is a common treatment for men with prostate cancer, particular in combination with androgen deprivation. However, various factors can limit the dose of radiation that can be administered, so the effect might be suboptimal. In this Review, the authors discuss how radiotherapy could be optimized by combining with other treatments in a multimodal approach, particularly in the setting of oligometastatic disease.