Reviews & Analysis

Bladder cancer outcomes differ between men and women. Elucidating this sexual dimorphism, genomic analyses found differing molecular subtype distributions and androgen response activities in muscle-invasive bladder cancer in men and women. Together with knowledge of cancer driver genes, biomarkers and clinical characteristics, these findings will hopefully lead to sex-based personalized research and management of bladder cancer.

Electronic cigarette (e-cigarette) use has risen rapidly over the past decade, despite limited knowledge of the risk of carcinogenesis and broader health implications. A recent systematic review summarizes the current evidence on carcinogen biomarkers in the urine of e-cigarette users. The findings warrant consideration and indicate that further insights are urgently needed.

Extirpative surgery for all patients with upper tract urothelial carcinoma (UTUC) risks overtreatment and associated morbidity. Endoscopic approaches are particularly applicable for low-risk disease albeit with the potential for ipsilateral upper tract recurrence. Adjuvant and ablative intracavitary therapies are current and future strategies that could improve disease outcomes and increase adoption of kidney preservation for UTUC.

A subgroup analysis of the RTOG 9601 trial, which stratified participants according to their pretreatment serum PSA levels, suggests disparate responses to therapy and potentially concerning cardiac and neurological effects in some men. However, subgroup analyses are notoriously difficult to interpret and the data should be considered with caution before changes are made to clinical practice.

A pilot trial of low-carbohydrate diet after definitive treatment for localized prostate cancer stopped early owing to futility but provides intriguing results in secondary analyses. The study offers an important opportunity to highlight caveats in data interpretation and to consider requirements for successful future research on dietary interventions in men with prostate cancer.

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.

A new trial evaluated whether neoadjuvant use of the tumour vaccine GVAX plus cyclophosphamide with androgen deprivation therapy (ADT) would augment antitumour immunity. ADT alone led to increased CD8⁺ T cell infiltration but also increases in regulatory cell populations. The results suggest that ADT should be used with treatments targeting the recruitment and persistence of these regulatory populations.

SPOP is involved in tumorigenesis by promoting ubiquitination and degradation of its substrates in human cancers. Wang et al. describe the regulation of expression and function of SPOP and discuss its roles in prostate and kidney cancers, focusing on various SPOP substrate proteins. They also highlight SPOP targeting as a potential therapeutic strategy.

In this Review, Meeks et al. summarize heterogeneity in bladder cancer and how it affects tumour biology and clinical care. They describe current knowledge of tumour evolution, genomic heterogeneity and different tumour subtypes, as well as morphological heterogeneity seen in variant bladder cancer histology. They also discuss the influence of heterogeneity on treatment decision making, drug development and clinical trial design.

A new study reports the 5-year patient-reported outcome data from a population-based cohort of men with localized prostate cancer. These findings in conjunction with data on survival, treatment burden and treatment cost can assist clinicians in explaining to newly diagnosed patients the likely effects of modern management options on quality of life.

Liquid biopsy techniques, especially the use of plasma circulating tumour DNA (ctDNA) analysis, are a convenient, fast and non-invasive approach to the diagnosis and monitoring of urological cancers, and could enable selection of targeted therapy before clinical and radiographic changes occur. In this Review, the authors discuss the uses of liquid biopsy and plasma ctDNA analysis in particular, and consider how it could be used in clinical practice now and in the future.

Management strategies used to treat prostate cancer often lead to treatment resistance, which can arise via a mechanism of cellular rewiring, whereby the tumour cell alters its signalling to escape the effects of therapy. Understanding these mechanisms could enable the development of improved and combination treatment regimens, to minimize treatment failures and improve outcomes.

Here, the authors discuss embryonic microRNAs that are highly expressed in testicular germ cell tumours, critically assess the clinical utility of monitoring these microRNAs in the circulation and compare their diagnostic performance with the classic serum tumour markers.

A randomized controlled trial has shown no statistically significant effect of low-intensity shockwave therapy when added to standard postprostatectomy pharmaceutical penile rehabilitation. Although this trial had a number of limitations, it adds to a body of literature that shows little effect of this therapy and emphasizes the need for development of effective therapeutic options for these patients.

Bader and McGuire review the current understanding of cancer metabolism with a focus on prostate cancer and the subversion of androgen receptor-driven metabolic programming to fuel oncogenic growth. They highlight diagnostic and therapeutic opportunities for clinical translation and future research directions.

In this Perspectives, a pioneer in the field of robotic radical prostatectomy describes the history of the technique and changing indications for its use, from an operation once considered useless, to one offered to almost all patients with low-risk disease, to a procedure that now has a role in advanced disease as part of a multimodal approach.

The female reproductive tract (FRT) harbours a site-specific microbiome. When dysbiosis of the FRT occurs, altered immune and metabolic signalling might lead to gynaecological cancer. In this Review, the authors discuss how dysbiosis could lead to malignancy and how cancer and its treatment can, in turn, affect the FRT microbiome. Finally, they consider how modulation of the microbiome might prove useful in improving responsiveness to cancer treatment and quality of life in women with gynaecological cancers.

No clear consensus exists for managing biochemically recurrent prostate cancer after prostatectomy. Interpretation of new data from the JCOG0401 trial warrants consideration of imaging techniques, prostate-specific antigen (PSA) levels at time of salvage radiotherapy (SRT), use of SRT ± salvage androgen deprivation therapy based on PSA levels, and the interval to biochemical failure.

The optimal treatment sequences to maximize the clinical benefit for patients with metastatic castration-resistant prostate cancer (mCRPC) have not been defined. A new prospective, randomized trial on optimal sequencing of enzalutamide and abiraterone acetate plus prednisone in mCRPC investigated whether one regimen resulted in superior outcomes.

In this Review, Chan and colleagues discuss the need for improved management options for hypospadias and describe advances in urethral tissue engineering and barriers to clinical application of tissue-engineered constructs in hypospadias repair.