Review Articles in 2016

In 2012, the United States Preventive Services Task Force issued a Grade D recommendation for PSA screening — in essence, a recommendation for cessation of prostate cancer screening in all US men. In this Review, the authors discuss the effect of this statement on prostate cancer incidence and dynamics, as well as changes in attitudes to screening of patients and health-care providers in the USA.

Recommendations based on high-level evidence for diagnosis, treatment and follow-up monitoring of upper tract urothelial carcinomas (UTUCs) are lacking and decision-making is often based on data from lower tract urothelial carcinoma. Here, Baard et al. review diagnostic tests for UTUC, describe efforts to improve lesion visualization, and propose an algorithm that integrates diagnosis, treatment, and clinical risk-stratification.

Lower urinary tract symptoms (LUTS) are common comorbidities in patients with Parkinson disease, or multiple system atrophy, and these can have considerable negative effects on patients' quality of life. In this Review, the authors describe the prevalence, diagnosis and management of LUTS in patients with PD or MSA, including the key differences in LUTS between patients with these disorders, which can, in some patients, enable a differential diagnosis.

Fournier's gangrene is a life-threatening urological emergency, which requires prompt treatment with fluid resuscitation, debridement, and reconstruction. In this Review, Hagedorn and Wessells describe the contemporary management of Fournier's gangrene, and discuss prognostic tools, therapeutics, and follow-up care of this rare but debilitating disorder.

Functional urological disorders, like their gastrointestinal counterparts, are interrelated and characterized by a chronic course and treatment resistance. Poor outcomes might be attributable to underlying psychological and psychiatric disorders, as the co-occurrence of functional disorders with mood and anxiety disorders is common. In this Review, the authors describe the hypothetical bladder–gut–brain axis, and explain how it is a useful framework under which this interaction can be studied.

FOX transcription factors are differentially expressed in bladder cancer subtypes and some are key regulators of embryonic bladder development. Yamashita et al. describe the specific roles of FOX genes and proteins in development and differentiation, and highlight functions in bladder cancer pathogenesis.

Circulating tumour cells (CTCs) have been studied as biomarkers of a number of urological cancers, although the data are strongest in prostate cancer. CTCs have potential clinical applications in early cancer detection, disease staging, monitoring for recurrence, prognostication, and therapy selection, and might help identify which patients are most likely to respond to androgen-pathway targeted therapies for prostate cancer. In this Review, Gorin and colleagues consider the evidence for a role of CTCs in prostate, bladder, and kidney cancer, and discuss their potential clinical applications.

The endothelial transcription factor GATA2 has been reported to have a key role in driving prostate cancer aggressiveness. GATA2 overexpression in prostate cancer increases cellular motility and invasiveness, proliferation, tumorigenicity, and resistance to standard therapies. Thus, GATA2 is a highly attractive target for the development of novel treatments against lethal prostate cancer.

Treatment with androgen-deprivation therapy can delay the progression of prostate cancer. However, acquired resistance to such approaches is very common. Here the authors describe the role of androgen synthesis pathways, including the specific relevance of each individual pathway, to the development of castration-resistant prostate cancer.

MicroRNA secretion pathways are dysregulated in cancer, making them attractive candidate molecules for liquid biopsies and studies have shown that they are noninvasive diagnostic, prognostic and surveillance markers in urological carcinomas. However, methodological and analytical pitfalls exist and require addressing to enable future translation of microRNA analysis into clinical practice.

Several observational studies support the hypothesis that statin use reduces the risk of advanced prostate cancer. In this Review, the authors discuss molecular mechanisms that might determine this effect, as well as data from clinical studies on associations between statin use and various prostate cancer outcomes, highlighting areas that require further research.

Urological complications remain among the most common, and the most bothersome of all complications in patients with a previous spinal cord injury. Minimizing the risks of these various complications, including incontinence, urinary retention, urinary tract infection and bladder cancer requires sustainable long-term management. In this Review, the author describes the optimal management strategy, while outlining the various unmet needs in the management of these patients.

The introduction of partial nephrectomy for the removal of small renal masses has enabled preservation of patients' renal function. However, this technique involves clamping of the renal hilum, resulting in ischaemia. In the past 5 years, researchers have developed a variety of techniques described as 'zero ischaemia'. Here the authors describe these various techniques and their outcomes, highlighting a need for standardized nomenclature and outcome measures.

A need for improved serum diagnostic tests for testicular germ cell tumours (GCTs) exists owing to the unsatisfactory performance of currently used markers. In this Review, Murray and colleagues discuss the current serum diagnostic tests for testicular GCTs, including α-fetoprotein, human chorionic gonadotrophin and lactate dehydrogenase, and the future use of novel universal biomarkers such as microRNAs.

A diagnosis of oligometastatic prostate cancer has become increasingly common, as diagnostic techniques have become more effective. However, the optimal management of patients with oligometastatic disease, and even the exact definition of oligometastasis itself, remains unclear. In this Review, Tosoian and colleagues examine the available data and offer their expert opinion on diagnosis, definition and management of the oligometastatic state.

The management of upper-tract urinary stones has dramatically changed towards an increase in the use of ureteroscopic treatment, driven by technological advances. In this Review, Weiss and Shah discuss the unique advantages and disadvantages of the two basic principles for treating stones ureteroscopically — dusting and basketing.

The prostate is an immune-competent organ and several stimuli have been identified as possible triggers for dysregulation of the prostatic immune system via molecular pathways involving the development of inflammatory infiltrates. From a pathophysiological standpoint, subsequent tissue damage and chronic tissue healing could result in the development of BPH nodules. In this Review, the authors discuss the immunopathology of BPH and consider its links to prostate cancer and other disorders from an immunological viewpoint.

Focal therapy is an emerging treatment option that involves the focal ablation of prostate cancer with preservation of surrounding healthy tissue, which might result in reduced morbidity. In this Review the authors discuss the controversy surrounding optimal patient selection, preoperative tumour localization strategies and the lack of long-term oncological data for focal therapy modalities.

Care must be taken to limit the long-term risks of treatment of stage I testicular germ cell tumours (TGCT) as long-term survival is ∼99%. The management of this disease remains controversial as the options are to overtreat to prevent relapse, or to observe and treat only patients who experience disease relapse. In this Review, Chovanec and colleagues discuss the options for the management of clinical stage I TGCT.

Proteomic and biochemical studies on cervical-vaginal fluid (CVF) have revealed that it contains several members of the tissue kallikrein-related peptidase (KLK) family. The roles of KLKs in the lower female reproductive system are not fully understood. In this Review, Muytjens and colleagues discuss the putative roles of KLKs in vaginal fluid and how increased understanding of their function could result in new diagnostic and therapeutic modalities.