Reviews & Analysis

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.

Immune system activation is necessary for BCG-mediated tumour immunity in non-muscle-invasive bladder cancer. However, mounting evidence supports the notion that dysfunctional activation, in the form of immune exhaustion, might contribute to BCG failure. Thus, an exhaustion signature, arising in treated tumours, could act as a predictive marker for BCG therapy.

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.

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.

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.

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.

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.

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.

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.

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.

Genetics has a role in predisposition towards prostate cancer, and an accurate prediction of prostate cancer risk can be made using polygenic risk scores. New evidence suggests that this risk is modifiable through lifestyle changes, but only in men at a high genetic risk of developing prostate cancer.

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 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.