Reviews & Analysis

For the management of bladder cancer, 2018 has been characterized by deepened knowledge on the molecular basis of invasive bladder cancer and its potential interaction with existing therapies, optimization of the use of immune checkpoint inhibitors, and emerging early signals on new therapeutic classes for advanced disease.

This Review describes the key insights into urologic chronic pelvic pain syndrome (UCPPS) from the first phase of Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network studies and highlights their implications for understanding the pathophysiological basis and clinical management of UCPPS.

2018 has been an exciting year for imaging in urology, especially in the field of prostate cancer. In this context, multiparametric MRI and molecular imaging targeting prostate-specific membrane antigen provide practice-changing developments for detection and diagnostic work-up.

The treatment of metastatic kidney cancer is rapidly evolving with the shift from immune checkpoint inhibitor monotherapy to combination therapy. In 2018, the combination of nivolumab–ipilimumab received regulatory approval and multiple positive clinical trials were reported with combinations of PD-1 or PD-L1 inhibitors in conjunction with antiangiogenic drugs.

Since the discovery and confirmation of the human urobiome, highly influential studies to characterize this microbial community and understand how it relates to human health and disease have been undertaken. Technological advances will improve information about the status of the urobiome for clinicians.

The extent of pelvic lymph node dissection at the time of radical cystectomy is debated as it might affect oncological outcomes in patients with bladder cancer. Gschwend et al. now demonstrate that the survival benefit is small and that the study might need to be repeated with a larger cohort.

Preliminary results from TRITON2 demonstrate efficacy of the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib in ~50% of patients with metastatic castration-resistant prostate cancer and inactivation of BRCA1/BRCA2. However, those with ATM and CDK12 mutations do not seem to benefit. An improved homologous recombination deficiency test must be developed and alternative treatments defined for these subsets of patients.

This Review discusses the challenges in accurately identifying rare prostate circulating tumour cells or bone marrow-derived disseminated tumour cells and the resulting need for prostate-specific, sensitive biomarkers for the detection of these cells in liquid biopsy samples.

In this Review, the authors describe the current mechanistic understanding of infection stone formation and growth, including the influence of the organic matrix, microorganisms, and biofilms, highlighting the medical implications of these insights and the importance of multidisciplinary management approaches.

Urinary extravasation occurs in ~30% of patients with high-grade renal trauma, but the lack of evidence-based guidelines complicates its clinical management. Here, the authors discuss the diagnosis and management of urinary extravasation, highlighting important knowledge gaps and future research directions.

Immunotherapy and tumour microenvironment modulation are potential new treatment approaches for metastatic prostate cancer, but patient selection might be key to delivering therapeutic benefit. In the past year, four studies have suggested that DNA mismatch repair alterations and CDK12 aberrations are biomarkers of response to immune checkpoint inhibitors.

Nonoperative management is the only treatment option for Peyronie’s disease in the acute phase of the disease, when surgery is contraindicated. In this Review, Tsambarlis and Levine discuss the oral and topical therapies that have been shown to be efficacious and provide recommendations for their use.

The penis is a diverse and rapidly evolving structure, much more complex than its fundamental function — sperm transfer — would seem to require. In this Review, experts in the field discuss the drivers of penis evolution, and consider how the penis might be an ideal characteristic on which to focus in studies to link phenotype with genotype.

Matta et al. report that men with prostate cancer who underwent surgery or radiotherapy, but not active surveillance, had greater odds of receiving antidepressants than controls. However, methodological limitations preclude the interpretation of a psychological benefit for men on active surveillance. Screening for distress and referral to evidence-based intervention should be a priority.

Transgender persons can be affected by sexual dysfunctions before, during, after, because of, and despite therapy. In this Review, experts in the field discuss trans sexuality across the gender dysphoric spectrum, and suggest ways in which trans persons can be supported in their sexuality and sexual function.

A recently published study has evaluated metabolism in human clear cell renal carcinomas (ccRCCs) using intraoperative [¹³C]glucose infusion during surgical procedures. The findings demonstrate aerobic glycolysis and repression of the Krebs cycle, confirming the existence of the Warburg effect in ccRCC tumours in vivo.

In this Review, the authors describe the current preclinical research into stem cell therapy for the treatment and prevention of penile fibrotic disorders, including Peyronie’s disease, urethral stricture and corpora cavernosa fibrosis, and highlight their specific mechanisms of antifibrotic activity.

In this Review, the authors describe the pathogenesis of uncomplicated urinary tract infections (UTIs). They discuss the need for nonantibiotic treatments and explore the nonantibiotic management options for the prevention and management of recurrent UTI.

Patients with stage T1 bladder cancer require meticulous management owing to their high-risk of recurrence, progression and death. Here, Jordan and Meeks describe the natural history, diagnosis, and treatment of T1 bladder cancer, highlighting key challenges and areas of future investigation.

The low biomass of the urinary microbiota presents methodological challenges for studying their role in urological diseases. Here, the authors describe methods for urinary microbiota profiling, and discuss important technical considerations for sampling, DNA sequencing, data processing and downstream analysis.