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Reply to Harry Herr's Letter to the Editor re: Marko Babjuk, Andreas Böhle, Maximilian Burger, et al. EAU Guidelines on Non–muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2016.05...

Refers to article:

EAU Guidelines on Non–Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016

Marko Babjuk, Andreas Böhle, Maximilian Burger, Otakar Capoun, Daniel Cohen, Eva M. Compérat, Virginia Hernández, Eero Kaasinen, Joan Palou, Morgan Rouprêt, Bas W.G. van Rhijn, Shahrokh F. Shariat, Viktor Soukup, Richard J. Sylvester and Richard Zigeuner

Accepted 30 May 2016

Footnotes

a Department of Urology, Hospital Motol, Second Faculty of Medicine, Charles University, Prague, Czech Republic

b Department of Urology, Caritas St. Josef Medical Centre, University of Regensburg, Regensburg, Germany

c Department of Pathology, Hôpital La Pitié-Salpétrière, UPMC, Paris, France

d Department of Urology, Fundació Puigvert, Universidad Autónoma de Barcelona, Barcelona, Spain

e AP-HP, Hôpital La Pitié-Salpétrière, Service d’Urologie, Paris, France

f UPMC University Paris 06, GRC5, ONCOTYPE-Uro, Institut Universitaire de Cancérologie, Paris, France

g Department of Surgical Oncology (Urology), Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands

h Medical University of Vienna, Vienna General Hospital, Vienna, Austria

i European Association of Urology Guidelines Office, Brussels, Belgium

j Department of Urology, Medical University of Graz, Graz, Austria

k Urology Clinic, Citta della Salute e della Scienza di Torino, University of Studies of Turin, Turin, Italy

l Department of Urology, North Hampshire Hospital, Basingstoke, Hampshire

Corresponding author. Department of Urology, Hospital Motol, Second Faculty of Medicine, Charles University, V Úvalu 84, Praha 5, 15006, Czech Republic. Tel. +420 224434801; Fax: +420 224434821.

Article information

PII: S0302-2838(16)30881-8
DOI: 10.1016/j.eururo.2016.11.029
© 2016 Published by Elsevier B.V.

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A Systematic Review and Meta-analysis Comparing the Effectiveness and Adverse Effects of Different Systemic Treatments for Non-clear Cell Renal Cell Carcinoma

Abstract Context

While vascular endothelial growth factor-targeted therapy and mammalian target of rapamycin inhibition are effective strategies in treating clear cell renal cell carcinoma (ccRCC), the most effective therapeutic approach for patients with non-clear cell RCC (non-ccRCC) is unknown.

Objective

To systematically review relevant literature comparing the oncological outcomes and adverse events of different systemic therapies for patients with metastatic non-ccRCC.

Evidence acquisition

Relevant databases including MEDLINE, Embase, and the Cochrane Library were searched up to March 24, 2016. Only comparative studies were included. Risk of bias and confounding assessments were performed. A meta-analysis was planned for and only performed if methodologically appropriate; otherwise, a narrative synthesis was undertaken.

Evidence synthesis

The literature search identified 812 potential titles and abstracts. Five randomized controlled trials, recruiting a total of 365 patients, were included. Three studies compared sunitinib against everolimus, one of which reported the results for non-ccRCC as a subgroup rather than as an entire randomized cohort. Individually, the studies showed a trend towards favoring sunitinib in terms of overall survival and progression-free survival (PFS; Everolimus versus Sunitinib in Patients with Metastatic Non-clear Cell Renal Cell Carcinoma hazard ratio [HR]: 1.41, 80% confidence interval [CI] 1.03–1.92 and 1.41, 95% CI: 0.88–2.27, Evaluation in Metastatic Non-clear Cell Renal Cell Carcinoma HR: 1.16, 95% CI: 0.67–2.01, Efficacy and Safety Comparison of RAD001 Versus Sunitinib in the First-line and Second-line Treatment of Patients with Metastatic Renal Cell Carcinoma HR: 1.5, 95% CI: 0.9–2.8), but this trend did not reach statistical significance in any study. Meta-analysis was performed on two studies which solely recruited patients with non-ccRCC reporting on PFS, the results of which were inconclusive (HR: 1.30, 95% CI: 0.91–1.86). Sunitinib was associated with more Grade 3–4 adverse events than everolimus, although this was not statistically significant.

Conclusions

This systematic review and meta-analysis represent a robust summary of the evidence base for systemic treatment of metastatic non-ccRCC. The results show a trend towards favoring vascular endothelial growth factor-targeted therapy for PFS and overall survival compared with mammalian target of rapamycin inhibitors, although statistical significance was not reached. The relative benefits and harms of these treatments remain uncertain. Further research, either in the form of an individual patient data meta-analysis involving all relevant trials, or a randomized controlled trial with sufficient power to detect potential differences between treatments, is needed.

Patient summary

We examined the literature to determine the most effective treatments for advanced kidney cancer patients whose tumors are not of the clear cell subtype. The results suggest that a drug called sunitinib might be more effective than everolimus, but the statistics supporting this statement are not yet entirely reliable. Further research is required to clarify this unmet medical need.

Take Home Message

In the treatment of patients with metastatic non-clear cell renal cell carcinoma, the systematic review and meta-analysis found numerically superior overall survival and progression-free survival for sunitinib in comparison with everolimus, although the findings did not reach statistical significance. Both agents have relatively modest effectiveness in non-clear cell renal cell carcinoma subtypes.

Keywords: Non-clear cell renal cell carcinoma, Papillary, Chromophobe, Sunitinib, Everolimus, Systematic review.

Footnotes

a Department of Urology, Cabueñes Hospital, Gijón, Spain

b Department of Urology, Sunderby Hospital, Sunderby, Sweden

c Department of Urology, University Hospital Hamburg Eppendorf, Hamburg, Germany

d Department of Urology, Coimbra University Hospital, Coimbra, Portugal

e Academic Urology Unit, University of Aberdeen, Aberdeen, UK

f Department of Urology, Aberdeen Royal Infirmary, Aberdeen, UK

g Department of Cancer Medicine, Institut Gustave Roussy, Villejuif, France

h Department of Urology, University of Rennes, Rennes, France

i Division of Urology, University of Texas Medical School at Houston, Houston, TX, USA

j Department of Urology, Skåne University Hospital, Malmö, Sweden

k Patient Advocate International Kidney Cancer Coalition (IKCC), University Medical Centre Utrecht, Department of Nephrology and Hypertension, Utrecht, The Netherlands

l Department of Urology, Faculty Hospital and Faculty of Medicine in Pilsen, Charles University in Prague, Prague, Czech Republic

m Department of Urology and Urologic Oncology, Hannover Medical School, Hannover, Germany

n Department of Urology, University Hospital Schleswig-Holstein, Lübeck, Germany

o The Royal Free NHS Trust and Barts Cancer Institute, Queen Mary University of London, London, UK

p Department of Urology, Ludwig-Maximilians University, Munich, Germany

q Division of Urology, Maggiore della Carità Hospital, University of Eastern Piedmont, Novara, Italy

r Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden

s Department of Urology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands

Corresponding author. The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Division of Surgical Oncology, Department of Urology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Tel. +31 20 512 2553; Fax: +31 20 512 2554.

Article information

PII: S0302-2838(16)30853-3
DOI: 10.1016/j.eururo.2016.11.020
© 2016 European Association of Urology, Published by Elsevier B.V.

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Validation of a Contemporary Five-tiered Gleason Grade Grouping Using Population-based Data

Abstract

This population-based study assesses whether a proposed five-tiered Gleason grade grouping (GGG) system predicts prostate cancer–specific mortality (PCSM). Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 331 320 prostate cancer patients who had primary and secondary Gleason patterns diagnosed between January 2006 and December 2012. We used the Fine and Gray proportional hazards model for subdistributions and the corresponding cumulative incidence to quantify the risk of PCSM. We found that the risk of PCSM approximately doubled with each GGG increase. Among men who underwent radical prostatectomy and using GGG1 (Gleason score ≤6) as the reference group, the adjusted hazard ratio for PCSM was 1.13 (95% confidence interval [CI] 0.83–1.54) for GGG2, 1.87 (95% CI 1.33–2.65) for GGG3, 5.03 (95% CI 3.59–7.06) for GGG4, and 10.92 (CI 8.03-14.84) for GGG5. Similar patterns were observed regardless of the type of primary cancer treatment received or clinical stage. In summary, our study, with large, racially diverse populations that reflect real world experiences, demonstrates that the new five-tiered GGG system predicts PCSM well regardless of treatment received or clinical stage at diagnosis.

Patient summary

In this report we examined prostate cancer mortality using the new five-tiered cancer grading system using data for a large US population. We found that the new five-tiered cancer grading system can predict prostate cancer–specific mortality well, regardless of the type of primary cancer treatment and clinical stage. We conclude that this new five-tiered cancer grading system is useful in guiding treatment decisions.

Take Home Message

Our study used patients identified from 18 US cancer registries to validate a proposed five-tiered Gleason grade grouping (GGG) system. This is the first study to show that the five-tiered GGG system predicts prostate cancer–specific mortality well.

Keywords: Gleason score, Prostate cancer, Population-based study.

Footnotes

a The School of Public Health, Rutgers, The State University of New Jersey, Piscataway, NJ, USA

b Janssen Global Services LLC, Raritan, NJ, USA

c Department of Surgery (Urology), University of Connecticut Health Center, Farmington, CT, USA

d The Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA

e Department of Medical Oncology, Sidney Kimmel Medical College and Jefferson College of Population Health, Thomas Jefferson University, Philadelphia, PA, USA

f Sidney Kimmel Cancer Center at Jefferson, Philadelphia, PA, USA

Corresponding author. Department of Medical Oncology, Sidney Kimmel Medical College, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107, USA. Tel. +1 215 5037970.

Article information

PII: S0302-2838(16)30883-1
DOI: 10.1016/j.eururo.2016.11.031
© 2016 European Association of Urology, Published by Elsevier B.V.

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UCLA researchers uncover new evidence linking inflammation and increased prostate cancer risk

MedicalNewsToday - Wed, 12/07/2016 - 08:00
UCLA researchers have discovered a previously unrecognized type of progenitor cell that, though rare in most regions of the human prostate, is found in uncommonly high numbers in inflamed areas of...
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Body composition may affect older women's risk of urinary incontinence

MedicalNewsToday - Wed, 12/07/2016 - 08:00
In a study of older women, the prevalence of stress- and urgency urinary incontinence (SUI and UUI) was at least two-fold higher among women in the highest category of body mass index (BMI) or fat...
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TSRI scientists find mechanism behind side effects in vision-loss treatment

MedicalNewsToday - Wed, 12/07/2016 - 08:00
A common class of drugs for vision loss may actually add to the problem in some patients, according to new research co-led by scientists at The Scripps Research Institute (TSRI).
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Changes in Weight and Metabolic Syndrome are Associated with Prostate Growth Rate Over a 5 Year Period : Reply

Urology (Gold Journal) In Press - Wed, 12/07/2016 - 00:00
We appreciate your comments and understand your question. The variables were statistically evaluated based on the assumption of normality (Figure 1). There were no interactions between most variables in the multivariable regression model. However, weight, BMI, and WC were found to have multicollinearity. Thus, we selected the weighted variables and removed BMI and WC, because we focused on the correlation between weight status and prostate volume. We agree that SBP and DBP are subject to individual fluctuations over time and can lead to regression dilution bias.
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Author Reply

Urology (Gold Journal) In Press - Wed, 12/07/2016 - 00:00
We presented our experience in the treatment of Peyronie disease (PD) with grafting procedure using porcine small intestinal submucosa. In spite of the average curvature of 80°, 82% of the patients had the curvature completely corrected. Dr. Drogo K. Montague addressed 2 main issues related to thesurgical treatment of PD: erectile dysfunction (ED) and penile shortening.
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Editorial Comment

Urology (Gold Journal) In Press - Wed, 12/07/2016 - 00:00
In this series of 28 men with Peyronie disease who had dorsal plaques and dorsal curvature, small intestinal submucosa grafting was done to correct dorsal curvature. Stretched penile length from the pubis to glans tip was measured by the same surgeon pre- and postoperatively. Pre- and postoperative erectile rigidity was subjectively evaluated by the patient and the surgeon as being either sufficient or not sufficient for penetration.
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Editorial Comment

Diuretic renography in neonates with prenatally detected hydronephrosis is integral to identifying obstructive causes requiring surgical intervention to preserve renal function from nonobstructive pelvicalicectasis that resolves spontaneously.1 Sussman et al address the limitations of over reliance on T½ of collecting system emptying after diuretic challenge despite use of the well-tempered renogram (reference 4 in article). In addition to differential renal function and T½ on initial diuretic renography, they examined CUP and C30, 2 parameters measuring the percent of emptying based on the region of interest count.
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Prediction of Clinical Outcomes in Prenatal Hydronephrosis: Importance of Gravity Assisted Drainage

In infants with SFU (Society for Fetal Urology) grade 3-4 congenital hydronephrosis, 99mTc-mercaptoacetyltriglycine diuretic renography assesses differential function and drainage half-time. We routinely also include the percent of radiotracer drained after 30 minutes of diuresis as well as after 15 minutes with the patient in the upright position. We investigated whether any 1 or more of these parameters on initial diuretic renography predicts persistent or worsening drainage parameters.
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Editorial Comment

Patients with locally inoperable primary tumors or advanced regional or distant metastatic penile cancer continue to represent a therapeutic dilemma.1 Neoadjuvant chemotherapy with subsequent surgical consolidation among responding patients can result in long-term survival in a subset. However, 40% to 50% of such patients do not respond and novel therapeutic strategies are required.2
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Editorial Comment

Therapeutic advances for penile squamous cell carcinoma are still awaited, mainly for advanced stages, due to the small available numbers and the difficulties in performing academic research in the field.1 Ottenhof et al provide the results of a large immunohistochemical analysis of PD-L1 expression in primary tumor samples from patients with penile squamous cell carcinoma. Results revealed that a high proportion of patients expressed PD-L1, mainly those with HPV negative tumors. Also, PD-L1 expression was negatively prognostic for a patient subgroup.
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Reply by Authors

We appreciate the valuable points raised by the comments. We agree that there is a need for uniformity and standardization of urodynamic interpretation, especially when multi-institutional trials are based on urodynamic outcomes. We are currently expanding our pilot study to multi-institutional participation and plan to incorporate our findings into a comprehensive standardized form guiding the interpretation of urodynamic studies.
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Editorial Comment

By performing this unique experiment (having members of the Division of Pediatric Urology at Vanderbilt, all of whom are well versed in reading urodynamic tracings, examine a series of representative studies), these authors have again demonstrated the need for developing uniformity in performing and interpreting urodynamic investigations.1
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Editorial Comment

Urodynamics is arguably the most critical urological test for children with neurogenic bladder. Our assessments of detrusor leak point pressure, of bladder compliance, of the bladder neck and external sphincter, and of detrusor overactivity form the basis of virtually all risk stratification algorithms for children with neurogenic bladder, including the CDC (Centers for Disease Control and Prevention) NSBPR and Newborn Urologic Protocol.1 Therefore, this report by Dudley et al is of paramount importance as it calls into question the reproducibility and objectivity of this test.
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Interrater Reliability in Pediatric Urodynamic Tracings: A Pilot Study

Urodynamic studies are crucial to neuropathic bladder management and they often determine surgical intervention. However, current evidence indicates that interpretations show poor agreement across physicians. We sought to determine the interrater reliability of urodynamic interpretation in our practice. We hypothesized that there would be strong correlation among pediatric urologists of similar training in a single academic practice.
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Author Reply

Urology (Gold Journal) In Press - Tue, 12/06/2016 - 00:00
We highly appreciate the editorial comments. Undescended testes are one of the most common congenital abnormalities of the genitourinary tract and intra-abdominal testes are a frequent condition treated by pediatric urologist. As we have mentioned in our article, the most appropriate approach for treatment of intra-abdominal testes using single-stage laparoscopic orchiopexy or laparoscopic staged Fowler–Stephens remains the practitioner's choice and continued research is needed to define the best surgical approach.
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Editorial Commentary Urology on Manuscript #URL-D-16-01008R1

Urology (Gold Journal) In Press - Tue, 12/06/2016 - 00:00
This retrospective review of a large series of intra-abdominal testes treated by single-stage and staged laparoscopic orchidopexy by multiple surgeons in a single institution offers some valuable insights into the treatment of this regularly encountered condition. The main contributions of their study are that abdominal undescended testes may be safely corrected by either single-stage or staged techniques, although some differences are noted: 4 of 50 atrophies (8%) in the single-stage group and an increased risk of unsatisfactory postoperative positioning (20%) vs 4 or 35 atrophies (11.4%) in the staged group and none with an abnormal postoperative positioning.
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Frailty and the role of obliterative versus reconstructive surgery for pelvic organ prolapse; a national study

To determine whether frailty affects the type of pelvic organ prolapse (POP) surgery performed and the odds of postoperative complications.
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