Review Articles in 2017

Several immune checkpoint inhibitors have been approved for use in metastatic urothelial carcinoma and could be clinically useful alone or in combination. However, they are associated with various immune-related adverse events and specific immune-related patterns of response. In this Review, the authors discuss the data supporting the use of checkpoint inhibition and consider how to optimize therapy to reduce and manage the effects of these therapies.

Despite its prevalence, sexual pain in women is poorly understood as it exists at the intersection of different biopsychosocial disciplines. In this Review, experts in the field describe how confusion remains at the nosological, aetiological, theoretical, methodological, and treatment levels and how a psychosocial approach can help to overcome this lack of consensus to improve theoretical models and effective treatments.

In this Review, Woldu and colleagues describe the implications of Rho GTPase signalling aberrations in the development of malignancy, including urothelial carcinoma. This signalling pathway has the potential for therapeutic targeting in this disease, but much work is necessary before current laboratory-based research can be translated into the clinic.

In this Review, the authors describe the role of the NO–sGC–cGMP signalling pathway in disease pathophysiology of urogenital tissue. They discuss advances in directly targeting sGC to enhance cGMP production independently using NO-independent stimulators and activators of sGC and the potential of these molecules for treating urogenital disorders.

Felsenstein and Theodorescu discuss advances in therapy response prediction in patients with bladder cancer based on tumour genomics. They summarize current clinical approaches and future requirements in personalized precision medicine including targeted as well as immunotherapeutic strategies.

Sfanos et al. discuss the potentially procarcinogenic role of prostatic infections and inflammation in prostate pathogenesis. They summarize findings that suggest that an aberrant microbiome together with an inflammatory microenvironment are involved in the initiation of prostate cancer precursor lesions.

Many emerging opportunities exist for microfluidics in male infertility diagnosis and treatment, and promising microfluidic approaches are under investigation for addressing male infertility. In this Review, the authors describe and discuss these approaches for sperm analysis and selection.

Owing to the limited operating space available, robot-assisted approaches have been rapidly adopted for procedures involving the retroperitoneal space. In this Review the authors describe the outcomes of patients undergoing robot-assisted procedures, including partial nephrectomy, radical nephrectomy, retroperitoneal lymph node dissection, nephroureterectomy and adrenalectomy, in addition to the potential of novel techniques.

WNT signalling pathway components are potentially important in prostate tumours, particularly in the development of castration-resistant prostate cancer and in the prostate tumour microenvironment. Here, Murillo-Garzón and Kypta describe our current understanding of WNT signalling in prostate cancer and discuss the potential of drugs that target this pathway.

The clinical relevance of variant histology in urinary bladder cancer has been increasing, resulting in new classifications of urothelial cancers by the WHO in 2016 and highlighting the importance of an accurate morphological description of pathological specimens for the therapeutic management of patients with bladder cancer.

Ginzburg et al. review the evolving role of focal ablative therapies in the management of small renal masses. They describe the techniques, the role of image guidance, pretreatment biopsy, and post-treatment surveillance, as well as data on safety, oncological, and functional outcomes.

Prostate cancer biology seems to be distinct among men of different ethnicities and races, as demonstrated by remarkable differences in the frequency ofERG oncogenic activation. In this Review, Sedarsky and colleagues discuss worldwide ERGalteration frequencies and consider how the data can be affected by variations in assay platforms and specimen types, as well as ethnic and geographical classifications, in order to realize the potential of precision medicine for men with prostate cancer.

High-grade prostatic intraepithelial neoplasia (HGPIN) and atypical glands suspicious for carcinoma are two prostate cancer diagnoses without standardized follow up and treatment pathways. In this Review, Tosoian and colleagues describe data that have shed light on these phenomena. The improved understanding of the implications of the presence of HGPIN and atypical glands on prostate biopsy means that clinical recommendations can be made for the management of patients with these diagnoses.

Patients with bladder cancer have a substantially increased risk of prostate cancer, compared with that of the general male population, and a diagnosis of concomitant prostate cancer can contribute to inferior outcomes, particularly in patients with muscle-invasive bladder cancer. Here, the authors describe the outcomes of such patients, in addition to the optimal treatment and management strategies and future research needs.

Low-intensity extracorporeal shockwave therapy (Li-ESWT) has gained popularity as a noninvasive treatment for erectile dysfunction (ED), with the potential to cure, rather than simply provide symptomatic relief. However, the quality of data regarding this treatment option is variable, and drawing conclusions is a challenge. In this Review, a team of expert authors describe the rationale and potential mechanisms of Li-ESWT for ED and discuss the available evidence for its clinical use.

Varicocele is the most common correctable cause of male infertility, but some men with varicoceles are able to father children, even without intervention, and so the link between varicoceles and male infertility remains a matter of debate. Oxidative stress seems to be a central mechanism of testicular damage; however, no single theory to explain the differential effect of varicoceles on infertility has been suggested. In this Review, a panel of expert authors discuss the epidemiology and pathophysiology of varicocele-related infertility, and consider the optimal treatment for men with varicocele.

Aberrations in telomere biology occur in prostate cancer tumorigenesis and progression. Graham and Meeker review the role of shortened telomeres in prostate tumour pathogenesis, including genomic instability and mutations. They describe the clinical utility of assessment of telomere dysfunction and the therapeutic potential of treatments targeting telomerase and telomeres.

Brachytherapy offers an excellent treatment option for definitive and salvage treatment of prostate cancer, with excellent oncological outcomes, limited toxic effects, and good quality of life for patients. However, use of prostate brachytherapy has been declining. In this comprehensive Review, Zaorsky and colleagues consider the evolution of brachytherapy from its inception to contemporary practice, from historical background to current indications and contraindications, underlying radiophysics and technical aspects, cost, and clinical outcomes.

Undescended testis — known as cryptorchidism — is one of the most common congenital abnormalities observed in boys, and is one of the few known risk factors for testicular cancer. The key factors that contribute to the occurrence of cryptorchidism remain elusive and a broad range of putative risk factors have been evaluated, but their plausibility is still in question.

Renal cell carcinoma (RCC) is largely percieved to be radioresistant, owing to the failure of several clinical trials involving fractionated radiotherapy. However, following the availability of new technologies, which enable the delivery of ablative doses of radiation, in fewer fractions, excellent responses have been observed among patients with RCC. In this Review, the authors describe the evidence supporting the use of ablative-dose radiotherapy, either alone, or in combination with other therapies in patients with RCC.