Reviews & Analysis

In this Perspective, Larcher et al. describe a dedicated treatment programme for Von Hippel–Lindau disease established at San Raffaele Hospital, which encompasses diagnosis, surveillance, treatment, research and outreach. The authors then discuss the benefits of care centralization for Von Hippel–Lindau disease and other rare diseases.

A subset of men with prostate cancer have elevated periprostatic androgens compared with levels in peripheral blood, which are associated with poor clinical outcomes after radical prostatectomy. This new paradigm for gonadal androgen physiology is termed ‘sneaky T’ phenomenon.

Antibiotic-resistant uropathogenic bacteria are becoming increasingly prevalent. In this Review, strategies for clinicians and researchers to address this challenge are delineated, including implementation of policies, stewardship practices, and the exploration of emerging therapeutic targets aimed at mitigating antibiotic resistance.

Urothelial cancer is the tenth most diagnosed cancer worldwide, and between 5% and 10% of patients have metastatic disease at diagnosis. Furthermore, up to 50% of patients are ineligible for cisplatin, the first-line treatment option, and require alternative options. In this comprehensive Review, the authors discuss the current and future therapeutic options for advanced urothelial cancer, including chemotherapeutics, targeted therapies and antibody–drug conjugates, and consider how these agents might change patient management.

In this Review, the authors discuss hypoxia signalling and therapeutic strategies targeting this pathway in renal cell carcinoma, with a specific focus on clear cell renal cell carcinoma, in which hypoxia signalling is primarily driven by Von Hippel–Lindau tumour suppressor (VHL) loss.

In this Review, the authors provide a comprehensive overview of the epidemiological characteristics, prognosis, biological mechanisms, detection methods and treatment options for liver metastasis in prostate cancer. Guidance for future research directions in the field is also provided.

Paternal substance use is associated with adverse effects on male reproductive health and offspring health outcomes. Comprehensive counselling by health-care providers and improved public health measures, especially targeting reproductive-age men, are needed.

Bladder cancer progression to microscopically distinct variants such as sarcomatoid, small cell, micropapillary and plasmacytoid is associated with more aggressive clinical behaviour than conventional carcinoma. Advances in molecular profiling led to the identification of molecular subtypes of bladder cancer and provided insights into disease progression to aggressive variants.

Ferroptosis induction is a promising new therapeutic strategy for advanced prostate cancer. In this Perspective, the authors discuss the interplay between ferroptosis and metabolism. Current efforts to target ferroptosis and combination therapies in prostate cancer, as well as emerging methods to monitor this process in patients, are also discussed.

In this Review, the authors describe mechanisms through which metabolic disorders and metabolic-related hormonal status affect testes metabolism, spermatogenesis and male fertility. New findings on metabolic-related epigenetic signatures and paternal transgenerational inheritance of metabolic disorders are also discussed.

Robot-assisted kidney transplantation is gaining momentum in kidney transplantation programmes as an alternative approach to patients with end-stage renal disease. In this Review, the authors provide an overview of available evidence on robot-assisted kidney transplantation, particularly in clinically challenging scenarios.

In this Perspective, the authors discuss the idea of targeting histone modifications in bladder cancer, providing a comprehensive overview of findings from preclinical and translational studies. Clinical trials in which the efficacy of molecules targeting histone modifiers was assessed in bladder cancer are also discussed.

The evaluation and management of patients with small renal masses continue to evolve as new data-driven evidence emerges. Contemporary research in biomarkers, imaging, and machine learning shows promise in improving the understanding of small renal masses.

RNA m⁶A modifications have emerged as an important contributor to urological cancer biology. Yang et al. highlight the multifarious roles of m⁶A modifications and discuss the knowledge gap between molecular understanding and clinical applications.

Oxidative stress and reactive oxygen species contribute to the pathophysiology of interstitial cystitis/bladder pain syndrome through their effects on molecular pathways. Here, the authors discuss these pathways, animal models of interstitial cystitis/bladder pain syndrome and treatment options for the disease.

In this Review, the authors describe the molecular profile of bladder cancer progression associated with the subtypes of this disease and comment on their potential diagnostic, prognostic and therapeutic importance.

In the SELENIB trial, selenium and vitamin E were compared with placebo as chemoprevention for non-muscle-invasive bladder cancer (NMIBC). No difference versus placebo was observed in recurrence-free interval (RFI) with selenium, but vitamin E was associated with worse RFI. Selenium and vitamin E cannot be recommended in chemoprevention for NMIBC. Furthermore, patients with NMIBC taking supplemental vitamin E should be made aware of its potential association with worse RFI.

Chromosomal instability is a hallmark of advanced prostate cancer. In this Review, the authors discuss the biological causes and paradoxical consequences of chromosomal instability, its potential clinical role in the stratification of prostate cancer aggressiveness and the development of novel treatment strategies.

African American men are disproportionately affected by prostate cancer in the USA. In this Review, the authors discuss the complex interplay of modifiable risk factors that might underlie the glaring prostate cancer disparities observed.

Muscle-invasive bladder cancer with clinically positive pelvic lymph nodes is a particular situation at the interface between localized and metastatic disease. In this Review, the authors discuss the advances and challenges of currently available strategies for the diagnosis and treatment of patients with muscle-invasive bladder cancer with clinically positive pelvic lymph nodes.