Review Articles in 2011

Recent evidence indicates an important role for the retinoblastoma (RB) tumor suppressor in the development of castration resistance in prostate cancer. In this Review, the authors describe the current state of knowledge regarding the implications of RB loss for disease progression, and consider the potential opportunities for developing RB as a metric with which to predict therapeutic response.

Urinary tract infections (UTIs) are common, costly and therapeutically challenging. Defining why certain individuals are protected from UTI while others have severe, recurrent infections has long been difficult, but progress is now being made, encouraging new approaches to risk assessment and therapy. Here, the authors describe how the innate immune system controls host resistance to UTI and how genetic variations in innate immunity affect UTI susceptibility.

Overactive bladder (OAB) is a challenging clinical condition and treatment can include behavioral therapy or antimuscarinic agents. A placebo effect has been reported in randomized controlled studies of antimuscarinic agents for OAB. In this Review, Mangera and colleagues assess the response to placebo in OAB and describe a positive placebo effect in OAB outcome parameters. Reasons for the placebo effect and its potential use will also be discussed.

Both the cure rate and morbidity of upper urinary tract urothelial carcinoma are sensitive to nuances of treatment so appropriate management is crucial. Here, Chromecki et al. discuss a number of potential prognostic factors—encompassing clinical characteristics, pathological factors and molecular markers—that might be utilized clinically to identify patients in need of more-aggressive therapy.

Epithelial-to-mesenchymal transition (EMT) is a process that occurs in normal vertebrate development, but has also been strongly implicated in tumor metastasis. In this Review, the authors describe the published evidence in support of a role for EMT—or an EMT-like state—in prostate cancer development and metastasis.

Postoperative radiotherapy can reduce the risk of biochemical recurrence in prostate cancer and improve survival. Three large randomized trials have provided evidence that adjuvant radiotherapy is effective; however, no such evidence exists for salvage radiotherapy, despite the fact that it can be as effective as adjuvant therapy in most men. In this Review, the authors discuss the evidence for and against both types of postoperative radiotherapy, and offer recommendations based on the available data.

The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signaling pathway has been implicated in the development of genitourinary cancers but it's exact role in cancer development, progression, and treatment responses remains unknown, as it can both inhibit and promote tumor growth. In this Review, the author describes the TRAIL apoptosis pathway and discusses how TRAIL-based therapies and combination treatments targeting TRAIL could be used to treat genitourinary malignancies.

Overactive bladder, in which patients have urinary urgency and incontinence, is a bothersome condition and treatment can be challenging. Here, in this Review, Barroso and Lordêlo discuss the use of electrical nerve stimulation for the treatment of overactive bladder in children. The mechanisms of action, technique, and available clinical results for this treatment modality are described.

Inhibition of 5α-reductase has the potential to be extremely useful in the treatment of prostate cancer. However, the two largest trials to investigate the use of such drugs showed that, although the overall incidence of cancer was reduced, detected tumors were more aggressive than in patients treated with placebo. In this Review, the authors consider the mechanism of 5α-reductase inhibitors in the treatment of prostate cancer, and discuss the controversies surrounding their use in clinical practice.

Controversy exists over the safety of testosterone replacement therapy (TRT) with regard to the initiation, promotion, aggressiveness, and progression of prostate cancer. In their Review, Goldenberg and colleagues argue the importance of classic early literature on the concept of a testosterone threshold level and the implications for use and safety of TRT, as well as describe the biological effects of TRT for testosterone deficiency.

Extended pelvic lymph node dissection has been shown to markedly improve oncologic outcomes in patients with urothelial carcinoma of the bladder, but the value of lymphadenectomy in the management of upper tract urothelial carcinoma (UTUC) is less clear. In this Review, the authors discuss whether routine regional lymph node dissection can be recommended for UTUC on the basis of the available evidence.

The clear-cell variant is the most common subtype of renal cell carcinoma (RCC) and, as discussed in this Review, accurate diagnosis of clear cell RCC is important and can be a challenge. Valera and Merino describe the clinical, pathological, and radiological features of clear cell RCC as well as the factors important to prevent misdiagnosis of this disease.

Over the last decade, NMR technology has become indispensible in the diagnosis and characterization of prostate cancer. In this Review, the authors discuss the evolution of NMR in prostate cancer, from its humble beginnings, up to today's use of NMR metabolomics.

Active surveillance is now an accepted management strategy for men with low-risk localized prostate cancer. Here, Lawrentschuk and Klotz provide an overview of the current issues concerning this somewhat contentious regime, including how best to select patients for active surveillance, which criteria should prompt intervention, and the concept of secondary chemoprevention.

In some men, increased age is associated with a reduction in testosterone, with a range of sexual, physical and psychological symptoms. Although this syndrome is referred to by many names, late-onset hypogonadism (LOH) is the most scientifically accurate. In this Review, Huhtaniemi and Forti summarize the pathophysiology, diagnostic criteria and treatment options for LOH, and discuss the controversies that surround the LOH diagnosis and the use of androgen replacement therapy.

Although renal cell carcinoma (RCC) is increasing in incidence and is associated with a poor outcome, there is no molecular test to identify which patients will relapse and who will respond to targeted therapies. In this Review, the authors discuss the biochemical, histological and genetic characteristics of RCC, and why these characteristics have not been translated into a useful prognostic and predictive test for patients with kidney cancer.

Matrix metalloproteinases (MMPs) are a family of enzymes that have a number of important functions, including regulation of the extracellular matrix, angiogenesis and apoptosis. MMP dysregulation has been implicated in several disease processes. In this Review, the authors describe the role of MMPs in bladder cancer, and how these enzymes seem to have potential as diagnostic and prognostic biomarkers or as targets for therapy in patients with this disease.

Gender dysphoria—a condition in which an individual has a severe discontent with the gender they were born with—can be treated with gender reassignment surgery. In this article, Selvaggi and Bellringer draw on their considerable experience to provide an overview of gender reassignment surgery. Both male-to-female and female-to-male surgeries and their associated complications will be discussed as well as the etiopathogenesis of gender dysphoria.

The surgical management of primary severe hypospadias remains controversial. In this Review, Castagnetti and El-Ghoneimi discuss the various preoperative, intraoperative and postoperative factors that might influence the outcome of surgery, and assess the possible advantages and drawbacks of such interventions.

Over the last decade, inguinal hernia has emerged as a major complication of radical retropubic prostatectomy, with an estimated incidence of 15–20%. Stranne and Lodding have assessed the available data and identified potential risk factors for the development of postoperative inguinal hernia. They also describe a number of possible prophylactic surgical maneuvers.