CA : A Cancer Journal for Clinicians

Background Nivolumab plus ipilimumab produced objective responses in patients with advanced renal-cell carcinoma in a pilot study. This phase 3 trial compared nivolumab plus ipilimumab with sunitinib for previously untreated clear-cell advanced renal-cell carcinoma. Methods We randomly assigned adults in a 1:1 ratio to receive either nivolumab (3 mg per kilogram of body weight) plus ipilimumab (1 mg per kilogram) intravenously every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks, or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The coprimary end points were overall survival (alpha level, 0.04), objective response rate (alpha level, 0.001), and progression-free survival (alpha level, 0.009) among patients with intermediate or poor prognostic risk. Results A total of 1096 patients were assigned to receive nivolumab plus ipilimumab (550 patients) or sunitinib (546 patients); 425 and 422, respectively, had intermediate or poor risk. At a median follo...

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Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma

Section I: Anatomy Surgical Anatomy of the Retroperitoneum, Kidneys, and Ureters Anatomy of the Lower Urinary Tract and Male Genitalia Section II: Clinical Decision Making Evaluation of the Urologic Patient: History, Physical Examination, and Urinalysis Urinary Tract Imaging: Basic Principles Outcomes Research Section III: Basics of Urologic Surgery Basic Instrumentation and Cystoscopy Basics of Laparoscopic Urologic Surgery Section IV: Infections and Inflammation Infections of the Urinary Tract-A. Schaeffer Inflammatory Conditions of the Male Genitourinary Tract Interstitial Cystitis and Related Disorders Sexually Transmitted and Associated Diseases Urological Implications of AIDS and Related Conditions Cutaneous Diseases of the External Genitalia Tuberculosis and Other Opportunistic Infections of the Genitourinary System Section V: Molecular and Cellular Biology Basic Principles of Immunology Molecular Genetics and Cancer Biology Tissue Engineering Perspectives for Reconstructive Surgery Section VI: Reproductive and Sexual Function Male Reproductive Physiology Male Infertility Surgical Management of Male Infertility Physiology of Erectile Dysfunction: Pathophysiology, Evaluation, Nonsurgical Management Epidemiology, Evaluation, and Nonsurgical Management of Erectile Dysfunction Prosthetic Surgery for Erectile Dysfunction Vascular Surgery for Erectile Dysfunction Peyronie's Disease Priapism Androgen Deficiency in the Aging Male Female Sexual Function and Dysfunction Section VII: Male Genitalia Neoplasms of the Testis Surgery of Testicular Tumors Tumors of the Penis Surgery of Penile and Urethral Carcinoma Surgery of the Penis and Urethra Surgery of the Scrotum and Seminal Vesicles Section VIII: Renal Physiology and Pathophysiology Renal Physiology and Pathophysiology Renovascular Hypertension Section IX: Upper Urinary Tract Obstruction and Trauma Pathophysiology of Obstruction Management of Upper Urinary Tract Obstruction Upper Urinary Tract Trauma Section X: Renal Failure and Transplantation Renal Transplantation Etiology, Pathogenesis, and Management of Renal Failure Section XI: Urinary Lithiasis and Endourology Urinary Lithiasis: Etiology, Epidemiology, and Pathophysiology Evaluation and Medical Management of Urinary Lithiasis Surgical Management of Upper Urinary Tract Calculi Ureteroscopy and Retrograde Ureteral Access Percutaneous Approaches to the Upper Urinary Tract Section XII: Neoplasms of the Upper Urinary Tract Renal Tumors Urothelial Tumors of the Upper Urinary Tract Urothelial Tumors of the Renal Pelvis and Ureter Open Surgery of the Kidney Laparoscopic Surgery of the Kidney Ablative Therapy for Renal Tumors Section XIII: The Adrenals Pathophysiology, Evaluation, and Medical Management of Adrenal Disorders Surgery of the Adrenals Section XIV: Urine Transport, Storage, and Emptying Physiology and Pharmacology of the Renal Pelvis and Ureter Physiology and Pharmacology of the Bladder and Urethra Pathophysiology, Categorization, and Management of Voiding Dysfunction Urodynamic and Video dynamic Evaluation of Voiding Dysfunction Neuromuscular Dysfunction of the Lower Urinary Tract Urinary Incontinence: Epidemiology, Pathophysiology, Evaluation, and Overview of Management The Overactive Bladder Pharmacologic Management of Storage and Emptying Failure Conservative Management of Urinary Incontinence: Behavioral and Pelvic Floor Therapy, Urethral and Pelvic Devices Electrical Stimulation and Neuromodulation in Storage and Emptying Failure Retropubic Suspension Surgery for Incontinence in Women Vaginal Reconstructive Surgery for Sphincteric Incontinence Pubovaginal Slings Tension-Free Vaginal Tape Procedures Injection Therapy for Urinary Incontinence Additional Treatment for Storage and Emptying Failure Geriatric Voiding Dysfunction and Urinary Incontinence Urinary Tract Fistulae Bladder and Urethral Diverticula Surgical Procedures for Sphincteric Incontinence in the Male: The Artificial Genitourinary Sphincter Perineal Sling Procedures Section XV: Bladder Lower Genitourinary Calculi and Trauma Urothelial Tumors of the Bladder Management of Superficial Bladder Cancer Management of Metastatic and Invasive Bladder Cancer Surgery of Bladder Cancer Laparoscopic Bladder Surgery Use of Intestinal Segments in Urinary Diversion Cutaneous Continent Urinary Diversion Orthotopic Urinary Diversion Genital and Lower Urinary Tract Trauma Lower Urinary Tract Calculi Section XVI: Prostate Molecular Biology, Endocrinology, and Physiology of the Prostate and Seminal Vesicles Etiology, Pathophysiology, and Epidemiology of Benign Prostatic Hyperplasia Natural History, Evaluation, and Nonsurgical Management of Benign Prostatic Hyperplasia Minimally Invasive and Endoscopic Management of Benign Prostatic Hyperplasia Retropubic and Superpubic Open Radical Prostatectomy Epidemiology, Etiology, and Prevention of Prostate Cancer Pathology of Prostatic Neoplasms Ultrasonography and Biopsy of the Prostate Tumor Markers in Prostate Cancer Early Detection, Diagnosis, and Staging of Prostate Cancer Definitive Therapy of Localized Prostate Cancer: Outcomes Expectant Management of Prostate Cancer Anatomic Retrograde Retropubic Prostatectomy Radical Perineal Prostatectomy Laparoscopic and Robotic Radical Prostatectomy and Pelvic Lymphadenectomy Radiation Therapy for Prostate Cancer Cryotherapy of Prostate Cancer Treatment of Locally Advanced Prostate Cancer Management of Rising Prostate-Specific Antigen after Definitive Therapy Hormonal Therapy for Prostate Cancer Management of Hormone-Resistant Prostate Cancer Section XVII: Pediatric Urology Normal and Anomalous Development of the Urinary Tract Renal Function in the Fetus Congenital Obstructive Uropathy Perinatal Urology Evaluation of Pediatric Urologic Patient Renal Disease in Childhood Urinary Tract Infections in Infants and Children Anomalies of the Kidney Renal Dysplasia and Cystic Disease of Kidney Anomalies and Surgery of the Ureteropelvic Junction Ectopic Ureter Vesicoureteral Reflux Prune-Belly Syndrome Exstrophy and Epispadias Complex Surgical Technique for One-Stage Exstrophy Reconstruction Bladder Anomalies in Children Posterior Urethral Valves and Other Urethral Anomalies Voiding Dysfunction in Children: Neurogenic and Non-neurogenic Urinary Tract Reconstruction Hypospadias Abnormalities of External Genitalia in Boys Abnormalities of Testis and Scrotum: Surgical Management Sexual Differentiation: Normal and Abnormal Surgical Management of Intersex Pediatric Oncology Pediatric Endourology and Laparoscopy Pediatric Genitourinary Trauma

Campbell-Walsh urology

In November, 2014, 65 prostate cancer pathology experts, along with 17 clinicians including urologists, radiation oncologists, and medical oncologists from 19 different countries gathered in a consensus conference to update the grading of prostate cancer, last revised in 2005. The major conclusions were: (1) Cribriform glands should be assigned a Gleason pattern 4, regardless of morphology; (2) Glomeruloid glands should be assigned a Gleason pattern 4, regardless of morphology; (3) Grading of mucinous carcinoma of the prostate should be based on its underlying growth pattern rather than grading them all as pattern 4; and (4) Intraductal carcinoma of the prostate without invasive carcinoma should not be assigned a Gleason grade and a comment as to its invariable association with aggressive prostate cancer should be made. Regarding morphologies of Gleason patterns, there was clear consensus on: (1) Gleason pattern 4 includes cribriform, fused, and poorly formed glands; (2) The term hypernephromatoid cancer should not be used; (3) For a diagnosis of Gleason pattern 4, it needs to be seen at 10x lens magnification; (4) Occasional/seemingly poorly formed or fused glands between well-formed glands is insufficient for a diagnosis of pattern 4; (5) In cases with borderline morphology between Gleason pattern 3 and pattern 4 and crush artifacts, the lower grade should be favored; (6) Branched glands are allowed in Gleason pattern 3; (7) Small solid cylinders represent Gleason pattern 5; (8) Solid medium to large nests with rosette-like spaces should be considered to represent Gleason pattern 5; and (9) Presence of unequivocal comedonecrosis, even if focal is indicative of Gleason pattern 5. It was recognized by both pathologists and clinicians that despite the above changes, there were deficiencies with the Gleason system. The Gleason grading system ranges from 2 to 10, yet 6 is the lowest score currently assigned. When patients are told that they have a Gleason score 6 out of 10, it implies that their prognosis is intermediate and contributes to their fear of having a more aggressive cancer. Also, in the literature and for therapeutic purposes, various scores have been incorrectly grouped together with the assumption that they have a similar prognosis. For example, many classification systems consider Gleason score 7 as a single score without distinguishing 3+4 versus 4+3, despite studies showing significantly worse prognosis for the latter. The basis for a new grading system was proposed in 2013 by one of the authors (J.I.E.) based on data from Johns Hopkins Hospital resulting in 5 prognostically distinct Grade Groups. This new system was validated in a multi-institutional study of over 20,000 radical prostatectomy specimens, over 16,000 needle biopsy specimens, and over 5,000 biopsies followed by radiation therapy. There was broad (90%) consensus for the adoption of this new prostate cancer Grading system in the 2014 consensus conference based on: (1) the new classification provided more accurate stratification of tumors than the current system; (2) the classification simplified the number of grading categories from Gleason scores 2 to 10, with even more permutations based on different pattern combinations, to Grade Groups 1 to 5; (3) the lowest grade is 1 not 6 as in Gleason, with the potential to reduce overtreatment of indolent cancer; and (4) the current modified Gleason grading, which forms the basis for the new grade groups, bears little resemblance to the original Gleason system. The new grades would, for the foreseeable future, be used in conjunction with the Gleason system [ie. Gleason score 3+3=6 (Grade Group 1)]. The new grading system and the terminology Grade Groups 1-5 have also been accepted by the World Health Organization for the 2016 edition of Pathology and Genetics: Tumours of the Urinary System and Male Genital Organs.

The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma: Definition of Grading Patterns and Proposal for a New Grading System.

Renal cell carcinoma (RCC) denotes cancer originated from the renal epithelium and accounts for >90% of cancers in the kidney. The disease encompasses >10 histological and molecular subtypes, of which clear cell RCC (ccRCC) is most common and accounts for most cancer-related deaths. Although somatic VHL mutations have been described for some time, more-recent cancer genomic studies have identified mutations in epigenetic regulatory genes and demonstrated marked intra-tumour heterogeneity, which could have prognostic, predictive and therapeutic relevance. Localized RCC can be successfully managed with surgery, whereas metastatic RCC is refractory to conventional chemotherapy. However, over the past decade, marked advances in the treatment of metastatic RCC have been made, with targeted agents including sorafenib, sunitinib, bevacizumab, pazopanib and axitinib, which inhibit vascular endothelial growth factor (VEGF) and its receptor (VEGFR), and everolimus and temsirolimus, which inhibit mechanistic target of rapamycin complex 1 (mTORC1), being approved. Since 2015, agents with additional targets aside from VEGFR have been approved, such as cabozantinib and lenvatinib; immunotherapies, such as nivolumab, have also been added to the armamentarium for metastatic RCC. Here, we provide an overview of the biology of RCC, with a focus on ccRCC, as well as updates to complement the current clinical guidelines and an outline of potential future directions for RCC research and therapy.

Renal cell carcinoma.

INTRODUCTION Laparoendoscopic single-site surgery (LESS) has emerged as a natural progression from standard laparoscopy toward minimization of surgical morbidity. We present our initial experience with LESS renal surgery in order to assess safety, feasibility, and early postoperative outcomes. MATERIALS AND METHODS Patients undergoing LESS renal surgery by a single surgeon from November 2008 to June 2010 were retrospectively identified. Safety, feasibility, and early outcomes were analyzed. Pain parameters were assessed using morphine equivalents used and visual analog pain scores (VAPS). RESULTS LESS procedures included 13 radical nephrectomy (1 bilateral), 5 simple nephrectomy (1 bilateral), 2 partial nephrectomy, 2 renal biopsy, and 1 renal cryoablation. Of 17 renal tumors, 15 were renal cell carcinoma and 2 had known renal vein involvement. Mean patient age was 55.4 years and mean BMI was 25.5 kg/m2. Mean operative time was 131 minutes (38-230), median estimated blood loss was 50 mL, and median length of stay was 2 days. There was one intraoperative transfusion and one conversion to conventional laparoscopy. The postoperative complication rate was 12% with two Clavien grade > 2 complications. Mean morphine equivalent dose of intravenous narcotics was 21.7 mg, and mean VAPS scores were 4.3, 3.5, and 2.9/10 on POD#0, #1, and day of discharge, respectively. CONCLUSIONS LESS surgery is safe and feasible for a wide variety of renal surgeries. Despite the selection bias of this early experience, postoperative outcomes and pain scores appear comparable to those reported for standard laparoscopy. Prospective studies comparing LESS to standard laparoscopic renal surgery are needed for definitive assessment.

Laparoendoscopic single-site surgery of the kidney: An initial experience

Long-term survival after radical prostatectomy for men with high pathologic gleason sum

Active Surveillance of Small Renal Masses: A Safe Management Strategy for Select Patients.

Background: Radical cystoprostatectomy (RCP) remains the gold standard for the treatment of muscle-invasive bladder cancer. There are limited data regarding the clinical impact and detection of PSA following complete prostatectomy or the need to monitor serum PSA in patients with benign prostate pathology at time of RCP. The purpose of our study was to analyze the postoperative PSA characteristics of men without prostate cancer who underwent a RCP for bladder cancer. Methods: The demographic, clinical and pathologic data were reviewed on 138 men who underwent RCP for bladder cancer from 1994 to 2008. Patients with known or incidentally discovered prostate cancer on final pathology were excluded from this study, and postoperative serum PSA values were reviewed in the remaining men. Results: The median age of the study population was 64 years (range 40–84). At a mean follow-up of 40.7 months, 137 (99.3%) of patients had an undetectable serum PSA. The one (0.7%) case in which serum PSA was not undetectable underwent an apex-sparing prostatectomy at the time of cystectomy. Conclusions: Serum PSA should remain undetectable for men with benign prostate pathology undergoing complete prostatectomy at the time of RCP. Elevated serum PSA following complete RCP in men with bladder cancer and pathologically confirmed benign prostate findings is rare. If the serum PSA is undetectable 3 months after RCP with benign prostate pathology, there is no need for continued PSA monitoring. These data support the notion that potential nonprostatic sources of PSA are clinically insignificant following complete removal of the prostate.

Is prostate-specific antigen surveillance necessary in men with benign prostate pathology following radical cystoprostatectomy for bladder cancer?

1703 impact of surgeon and hospital volume on short-term outcomes of percutaneous nephrolithotomy

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