Clear-cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer and its molecular pathogenesis is incompletely understood. Here we report an integrated molecular study of ccRCC in which ≥100 ccRCC cases were fully analyzed by whole-genome and/or whole-exome and RNA sequencing as well as by array-based gene expression, copy number and/or methylation analyses. We identified a full spectrum of genetic lesions and analyzed gene expression and DNA methylation signatures and determined their impact on tumor behavior. Defective VHL-mediated proteolysis was a common feature of ccRCC, which was caused not only by VHL inactivation but also by new hotspot TCEB1 mutations, which abolished Elongin C-VHL binding, leading to HIF accumulation. Other newly identified pathways and components recurrently mutated in ccRCC included PI3K-AKT-mTOR signaling, the KEAP1-NRF2-CUL3 apparatus, DNA methylation, p53-related pathways and mRNA processing. This integrated molecular analysis unmasked new correlations between DNA methylation, gene mutation and/or gene expression and copy number profiles, enabling the stratification of clinical risks for patients with ccRCC.

Introduction In the development of terminology of the lower urinary tract, due to its increasing complexity, the terminology for male lower urinary tract and pelvic floor symptoms and dysfunction needs to be updated using a male‐specific approach and via a clinically‐based consensus report. Methods This report combines the input of members of the Standardisation Committee of the International Continence Society (ICS) in a Working Group with recognized experts in the field, assisted by many external referees. Appropriate core clinical categories and a subclassification were developed to give a numeric coding to each definition. An extensive process of 22 rounds of internal and external review was developed to exhaustively examine each definition, with decision‐making by collective opinion (consensus). Results A Terminology Report for male lower urinary tract and pelvic floor symptoms and dysfunction, encompassing around 390 separate definitions/descriptors, has been developed. It is clinically‐based with the most common diagnoses defined. Clarity and user‐friendliness have been key aims to make it interpretable by practitioners and trainees in all the different specialty groups involved in male lower urinary tract and pelvic floor dysfunction. Male‐specific imaging (ultrasound, radiology, CT, and MRI) has been a major addition whilst appropriate figures have been included to supplement and help clarify the text. Conclusions A consensus‐based Terminology Report for male lower urinary tract and pelvic floor symptoms and dysfunction has been produced aimed at being a significant aid to clinical practice and a stimulus for research.

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This section contains papers from Japan, Austria, the UK, and joint papers from France, Denmark, Switzerland, Australia and the USA. A wide variety of lower urinary tract topics is covered, from BPH to overactive bladder and urodynamic stress incontinence. OBJECTIVE To verify the efficacy and safety of the new α1A‐adrenoceptor‐selective antagonist silodosin compared with tamsulosin and placebo in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). PATIENTS AND METHODS This randomized, double‐blind, placebo‐controlled study was conducted at 88 centres in Japan. Men aged ≥50 years with an International Prostate Symptom Score (IPSS) of ≥8, a quality‐of‐life (QoL) score of ≥3, a maximum urinary flow rate (Qmax) of <15 mL/s, a prostate volume of ≥20 mL and a postvoid residual urine volume of <100 mL were eligible for enrolment. Patients were randomized to receive silodosin 4 mg twice daily, tamsulosin 0.2 mg once daily, or placebo, for 12 weeks. The primary endpoint was the change in IPSS from baseline. Safety was assessed by adverse events, physical examination, vital signs and laboratory tests. RESULTS In all, 457 patients were randomized (silodosin 176, tamsulosin 192 and placebo 89). The change in the total IPSS from baseline in the silodosin, tamsulosin and placebo groups was −8.3, −6.8 and −5.3, respectively. There was a significant decrease in the IPSS vs placebo in the silodosin group from 1 week. In the early‐stage comparison, silodosin showed a significant decrease in IPSS vs tamsulosin at 2 weeks. The change in QoL from baseline was −1.7, −1.4 and −1.1 in the silodosin, tamsulosin and placebo groups, respectively; silodosin showed a significant improvement in the QoL score vs placebo. In the subgroup of patients with severe symptoms (IPSS ≥20) silodosin also gave a significantly better improvement than placebo (−12.4 vs −8.7). The incidence rates of adverse events and drug‐related adverse events were, respectively, 88.6%, 82.3% and 71.6% and 69.7%, 47.4% and 36.4%, respectively. The most common adverse event in the silodosin group was abnormal ejaculation, which occurred more often in the silodosin than in the tamsulosin group (22.3% vs 1.6%). However, only five men (2.9%) discontinued treatment for abnormal ejaculation. CONCLUSION Silodosin was generally effective in the absence of obtrusive side‐effects. This study suggests that silodosin is clinically useful for treating LUTS associated with BPH.