Review Articles in 2022

In this Review, mechanistic findings of growth inhibition by supraphysiological androgens in prostate cancer are described, and insights from the results of using supraphysiological testosterone and the future clinical development of bipolar androgen therapy as an option for prostate cancer are discussed.

This Review summarizes current knowledge regarding salvage high-dose chemotherapy in relapsed germ cell tumours. The authors outline data from phase I and II clinical trials, phase III randomized trials and retrospective datasets, discuss controversies and provide recommendations.

In this Review, the authors discuss the novel concept of the prognostic role of prostate-specific membrane antigen (PSMA)–PET across all prostate cancer disease states in the context of established prognostic tools and describe the future directions of research on the prognostic value of PSMA–PET.

In this Review, the authors provide a comprehensive overview of various in vitro, ex vivo and in vivo models of prostate cancer and discuss their respective advantages and limitations in the context of current needs and challenges in prostate cancer research and therapy.

The approval of immunotherapy agents to treat patients with metastatic renal cell carcinoma revolutionized the therapeutic landscape for this disease, but a large number of patients still do not experience objective and durable response, and biomarkers to identify response to immunotherapy are urgently needed. In this Review, the authors describe strength and limitations of currently available prognostic and predictive biomarkers in metastatic renal cell carcinoma and discuss emerging promising biomarkers that deserve further investigation.

Here, Goss et al. explore the diagnostic potential of male reproductive small extracellular vesicles and the practical approaches of implementing point-of-need and multianalyte diagnostics in infertility treatment, detailing microfluidic small extracellular vesicle isolation and analysis as an accessible and effective approach to achieving this outcome.

The unfolded protein response has an important role in prostate cancer tumorigenesis. Here, the authors discuss its involvement in prostate cancer development and progression, interactions with androgen receptor signalling, and the therapeutic implications for the treatment of metastatic disease.

In this Review, the authors analyse all the steps of the multiparametric MRI-guided prostate cancer diagnostic pathway, focusing on quality assurance systems to minimize variation in performance and discussing quality control measures to assess and mitigate poor quality throughout the process.

Evidence has suggested that the intestinal microbiome might have a role in maintaining oxalate homeostasis and kidney stone disease and that the urinary microbiome might also influence the induction of crystal formation and stone growth directly in the kidney. In this Review, the authors discuss the mechanisms by which these microbial populations contribute to stone disease and how they might be therapeutically targeted.

Stage I testicular germ cell tumour is restricted to the testicle and can be mostly cured by orchiectomy; however, many patients experience tumour relapse. In this Review, the authors describe advantages and limitations of the currently available predictive biomarkers of relapse in germ cell tumours, and discuss the need to identify new biomarkers to avoid patient overtreatment.

Premature ejaculation is a male disorder causing distress, bother, frustration and/or avoidance of sexual intimacy. Currently available therapies are not lasting and only mildly effective. In this Review, the authors summarize currently available approved and off-label treatments for premature ejaculation, and comprehensively discuss emerging therapeutic options.

Several studies over the past few decades have suggested that sperm quality varies by geographical region and might be subject to a temporal decline worldwide. However, the data supporting these conclusions have come from studies of various methodologies and heterogeneous populations, making them unreliable. In this in-depth Review, Chevrier and colleagues discuss the data surrounding discussion of spatiotemporal trends in semen parameters and consider how these trends and the factors promoting them interact.

Diabetic bladder dysfunction (DBD) is a common complication of diabetes. Hyperglycaemia-induced oxidative stress is thought to mediate functional changes in organs and tissues affected by DBD. In this Review, the authors provide an overview of mechanisms and consequences of oxidative stress, focusing on the role of diabetes-induced oxidative stress in generating dysfunctions at the level of the urothelium, smooth muscle contractility and nerve structures involved in DBD pathogenesis.

In this Review, Joshi and colleagues describe the immune landscape of penile cancer, examine existing and novel immune-based therapeutic targets, and discuss the future directions of immune-based therapies in penile cancer based on preclinical and clinical studies.

In this Review, the authors discuss the current evidence for the use of prostate-specific membrane antigen (PSMA) PET and whole-body (WB) MRI, consider the evolving use of PSMA PET-derived and WB MRI-derived quantitative biomarkers and make recommendations for future clinical trials of these modalities.

In this Review, the authors summarize current advances in our understanding of the roles of stroma and associated extracellular matrix during bladder cancer development, describing the bladder tumour microenvironment and introducing the concept of the metastatic tumour microenvironment.

Hyperactivation of innate immunity is a disease determinant in urinary tract infections (UTIs). Modulation of innate immunity has promise as a therapy for UTIs. In this Review, the authors discuss potential mechanisms and immunomodulatory therapeutic strategies in UTIs.

Standard-of-care management of renal cell carcinoma (RCC) relies on surgery for low-risk localized disease and systemic treatment for poor-prognosis metastatic tumours, but patients with high-risk localized tumours and with metastatic disease that has a good-to-intermediate prognosis are in a grey area for treatment. In this Review, the authors provide a comprehensive overview of the current knowledge on surgery and systemic treatment in the management of metastatic and localized RCC.

In this Review, Russo and Giri describe and discuss germline testing criteria, genetic testing strategies, genetically informed screening, precision management, delivery of genetic counselling or alternative genetic services and special considerations for men with prostate cancer.

In this Review, the authors describe our current knowledge of the consequences of SARS-CoV-2 infection on the urogenital system, discussing urological symptoms and damage to organs of the genitourinary tract induced by COVID-19 infection. Moreover, the effects of COVID-19 on male fertility and sexual health are discussed.