Reviews & Analysis

Biomarkers that can improve risk stratification of patients with prostate cancer are urgently needed. In this Review, Khoo et al. outline mass spectrometry technologies that enable the systematic discovery and targeted validation of protein-based biomarkers in prostate-associated fluids.

Anticholinergics are a common class of medication used in the treatment of overactive bladder. However, concerns have been raised over the potential association of anticholinergics and cognitive impairment or dementia. This Review discusses the clinical evidence and provides guidance for prescribing anticholinergics in at-risk populations.

Serum PSA testing can identify men with clinically significant prostate cancer but exposes many more men to the diagnosis of indolent tumours. Benafif and colleagues have published the results of the BARCODE1 pilot study, in which they propose using germline single-nucleotide polymorphisms to identify men with a genetic risk of developing prostate cancer. Based on their preliminary findings, changing the current prostate cancer screening paradigm will be a challenge.

Conventionally fractionated external beam radiotherapy is an effective treatment for localized prostate cancer, but long treatment programmes result in a substantial burden to patients and the health-care system, which is particularly problematic in low-income and middle-income countries (LMICs) where health-care resources might be scarce and patient funds limited. Here, the authors discuss the outcomes and benefits of hypofractionation — in terms of both oncology and economics — and how it could be used to improve prostate cancer care in LMICs.

Biochemical recurrence following radical prostatectomy for intermediate-risk and high-risk prostate cancer is common. However, not all patients with recurrence will die from their disease. This comprehensive Review from a multidisciplinary group discusses the optimal evaluation and management of these patients to ensure balance between treatment-related morbidity and cancer control.

Balancing diversity on panels at academic medical conferences demonstrates a commitment to the principles of diversity and inclusion. However, it seems we have a long way to go in urology, where two-thirds of sessions at major urology meetings still consist of all-male speaker panels.

Society guidelines recommend incorporating palliative care into standard oncological care. However, misconceptions regarding palliative care are common — notably, palliative care and treatments seeking to cure or prolong life are not mutually exclusive. In this article, the authors discuss the integration of palliative care into surgical urologic oncology and consider palliative care guidelines, indications for palliative care use, and how the field of urologic oncology can adopt best practices.

Senescent cells and their secretome — the senescence-associated secretory phenotype (SASP) — cause a systemic pro-inflammatory state, contributing to an inflammatory microenvironment. In this article, the authors discuss the presence of senescent cells and the SASP in the ageing prostate and the evidence for a role of senescence in BPH and prostate cancer, as well as possible therapeutic targeting of these pathways in the future.

Neuroendocrine prostate cancer predominantly develops from adenocarcinoma following a period of androgen suppressive treatment. Outcomes in patients with this disease are poor; the understanding of the molecular mechanisms behind its development will improve future targeted therapy options.

Chimeric antigen receptor T cell immunotherapy for prostate cancer has the potential to be combined with other treatment modalities, such as androgen deprivation therapy, radiotherapy or chemotherapy; furthermore, new developments could improve the efficacy of chimeric antigen receptor T cell therapy and this treatment could also be applied as focal therapy for this disease.

The treatment of patients with the PD1 inhibitor pembrolizumab yields benefit in the second-line metastatic urothelial cancer setting. Two new trials have studied pembrolizumab monotherapy in other patients with urothelial carcinoma: an open-label phase II trial has enrolled patients with high-risk BCG-refractory non-muscle-invasive disease, and a phase III trial has compared three first-line treatment options for patients with metastatic disease. However, these trials have shown conflicting results.

Testosterone replacement therapy for the treatment of primary hypogonadism in men is associated with multiple adverse effects including infertility. The re-establishment of testosterone-producing cell lineages using stem-cell-based therapy has had promising results in pre-clinical studies and could be used in transplantation therapy.

Despite the success of immune checkpoint inhibition (ICI) in other tumour types, the majority of ICI-treated patients with bladder cancer fail to respond. This lack of efficacy might be attributable to a lack of pre-existing immune reactive cells within the tumour immune microenvironment, which limits the efficacy of ICI. In this Review, Li and colleagues discuss how oncolytic virus therapy acts as a strategy to attract lymphocytes before implementation of ICI and consider the data supporting the use of combination approaches using oncolytic virotherapy with ICI in bladder cancer.

Exercise improves outcomes in prostate cancer, but the mechanisms behind this are poorly understood. This Review discusses exercise-induced blood alterations, with a focus on muscle-secreted myokines, which could have both direct and indirect effects on tumour proliferation.

Bacillus Calmette–Guérin (BCG) has been used to prevent tuberculosis for a century and is also a standard approach for the treatment of non-muscle-invasive bladder cancer. However, BCG also has a plethora of non-specific effects that occur via the induction of trained immunity and have raised the hypothesis that BCG vaccination could be used to protect against coronavirus disease 2019 (COVID-19). In this Perspective, the authors describe the history of BCG, discuss the mechanisms of its effects, and consider its potential role during the COVID-19 pandemic.

In this Review the authors describe advances in our understanding of the molecular determinants of urinary tract infection pathogenesis, focusing on specific host susceptibility factors and their consequences.

Radiotherapy is one of the most effective modalities for cancer treatment, but radiation-associated secondary malignancies are important potential morbidities. Here, we highlight a recent article that examines radiation-associated muscle-invasive bladder cancer and explore how we as clinicians should consider the management of secondary malignancies.

A new phase I clinical trial has demonstrated that belzutifan provides a route to sustained inhibition of hypoxia-inducible factor 2α in humans that is well tolerated and could be useful in the treatment of advanced clear cell kidney cancer.

Evidence for the existence of racial disparities in semen parameters is increasing, exemplified by a recent study in men from white, Black and Asian populations. However, reference standards for semen parameters might not account for these disparities.

Sperm analysis has a central role in diagnosing and treating male factor infertility. Emerging techniques have been developed that enable improved analysis of sperm motility, morphology and genetics to help overcome current limitations in accuracy and consistency, and improve sperm selection for infertility treatment.