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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
Accepted 30 May 2016Footnotes
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.
© 2016 Published by Elsevier B.V.
A Systematic Review and Meta-analysis Comparing the Effectiveness and Adverse Effects of Different Systemic Treatments for Non-clear Cell Renal Cell Carcinoma
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.
© 2016 European Association of Urology, Published by Elsevier B.V.
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.
© 2016 European Association of Urology, Published by Elsevier B.V.