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Urinary Bladder Neoplasms: HELP
Articles from Utah
Based on 57 articles published since 2008

These are the 57 published articles about Urinary Bladder Neoplasms that originated from Utah during 2008-2019.
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Editorial Circulating Tumor DNA in Bladder Cancer: Novel Applications and Future Directions. 2018

Maia, Manuel Caitano / Grivas, Petros / Agarwal, Neeraj / Pal, Sumanta K. ·Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. · Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA. · Division of Medical Oncology, University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA. · Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. Electronic address: spal@coh.org. ·Eur Urol · Pubmed #29097099.

ABSTRACT: -- No abstract --

2 Editorial Which checkpoint inhibitor? An embarrassment of riches for bladder cancer. 2017

Gill, David M / Sonpavde, Guru / Pal, Sumanta K / Agarwal, Neeraj. ·Department of Internal Medicine, Division of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA. · Division of Hematology & Oncology, University of Alabama Birmingham School of Medicine, Birmingham, AL 35294, USA. · Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA. ·Immunotherapy · Pubmed #28472906.

ABSTRACT: -- No abstract --

3 Editorial Bacillus Calmette-Guérin Manufacturing and SWOG S1602 Intergroup Clinical Trial. 2017

Meeks, Joshua J / Lerner, Seth P / Svatek, Robert S. ·Department of Urology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois. · Department of Urology, Baylor College of Medicine, Houston, Texas. · Department of Urology, UT Health San Antonio, San Antonio, Texas. ·J Urol · Pubmed #27992750.

ABSTRACT: -- No abstract --

4 Editorial Analysis of genetics to identify susceptibility to secondary malignancies in patients with bladder cancer. 2016

Lotan, Yair. ·Department of Urology, UT Southwestern Medical Center at Dallas, Dallas, TX, USA. ·BJU Int · Pubmed #27311549.

ABSTRACT: -- No abstract --

5 Editorial Adjuvant Chemotherapy for Bladder Cancer: Using Population-Based Data to Fill a Void of Prospective Evidence. 2016

Pal, Sumanta K / Agarwal, Neeraj / Grivas, Petros / Choueiri, Toni. ·City of Hope Comprehensive Cancer Center, Duarte, CA spal@coh.org. · Huntsman Cancer Institute, University of Utah, Salt Lake City, UT. · Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH. · Dana-Farber Cancer Institute, Boston, MA. ·J Clin Oncol · Pubmed #26786913.

ABSTRACT: -- No abstract --

6 Editorial Would the benefits of hexaminolevulinate fluorescence cystoscopy be eliminated if every patient received postoperative installation of intravesical chemotherapy? 2013

Lotan, Yair. ·Department of Urology, UT Southwestern Medical Center at Dallas, Dallas, TX, USA. yair.lotan@utsouthwestern.edu. ·BJU Int · Pubmed #24283995.

ABSTRACT: -- No abstract --

7 Review The use of blue light flexible cystoscopy with hexaminolevulinate & the diagnosis of bladder cancer. 2018

Clinton, Timothy N / Lotan, Yair. ·Department of Urology, UT Southwestern Medical Center in Dallas, TX 75390, USA. ·Future Oncol · Pubmed #29925279.

ABSTRACT: Blue light cystoscopy improves the detection of bladder cancer at time of transurethral resection of bladder tumor for nonmuscle-invasive bladder cancer. This has translated to decreased tumor recurrence. Given this improvement in rigid cystoscopy, the question remains whether the use of blue light flexible cystoscopy (BLFC) in the surveillance setting provides the same benefits. This review aims to evaluate the recently reported Phase III prospective multicenter study of BLFC which evaluated the detection of bladder cancer during surveillance, which in its earliest reporting demonstrated improved detection of bladder cancer. This study evaluated 304 patients with findings of 63 confirmed malignancies, with 13 (20.6%) only identified by BLFC (p < 0.0001). The question still remains whether the improved detection rate will translate to improved clinical outcomes. Further, studies will be necessary to determine which patients will benefit from BLFC, optimal ways to incorporate into surveillance strategies and cost-effectiveness.

8 Review Bladder cancer. 2017

Sanli, Oner / Dobruch, Jakub / Knowles, Margaret A / Burger, Maximilian / Alemozaffar, Mehrdad / Nielsen, Matthew E / Lotan, Yair. ·Department of Urology, UT Southwestern Medical Center at Dallas, Moss Building, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9110, USA. · Centre of Postgraduate Medical Education, Warsaw, Poland. · Section of Molecular Oncology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK. · Klinik für Urologie, Universität Regensburg, Regensburg, Germany. · Department of Urology, Emory University School of Medicine, Atlanta, Georgia, USA. · Department of Urology, University of North Carolina, Chapel Hill, North Carolina, USA. ·Nat Rev Dis Primers · Pubmed #28406148.

ABSTRACT: Bladder cancer is a highly prevalent disease and is associated with substantial morbidity, mortality and cost. Environmental or occupational exposures to carcinogens, especially tobacco, are the main risk factors for bladder cancer. Most bladder cancers are diagnosed after patients present with macroscopic haematuria, and cases are confirmed after transurethral resection of bladder tumour (TURBT), which also serves as the first stage of treatment. Bladder cancer develops via two distinct pathways, giving rise to non-muscle-invasive papillary tumours and non-papillary (solid) muscle-invasive tumours. The two subtypes have unique pathological features and different molecular characteristics. Indeed, The Cancer Genome Atlas project identified genetic drivers of muscle-invasive bladder cancer (MIBC) as well as subtypes of MIBC with distinct characteristics and therapeutic responses. For non-muscle-invasive bladder cancer (NMIBC), intravesical therapies (primarily Bacillus Calmette-Guérin (BCG)) with maintenance are the main treatments to prevent recurrence and progression after initial TURBT; additional therapies are needed for those who do not respond to BCG. For localized MIBC, optimizing care and reducing morbidity following cystectomy are important goals. In metastatic disease, advances in our genetic understanding of bladder cancer and in immunotherapy are being translated into new therapies.

9 Review Long non-coding RNAs in anti-cancer drug resistance. 2017

Chen, Qin-Nan / Wei, Chen-Chen / Wang, Zhao-Xia / Sun, Ming. ·Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China. · Department of Bioinformatics and Computational Biology, UT MD Anderson Cancer Center, Houston, Texas, United States of America. ·Oncotarget · Pubmed #27713133.

ABSTRACT: Chemotherapy is one of the basic treatments for cancers; however, drug resistance is mainly responsible for the failure of clinical treatment. The mechanism of drug resistance is complicated because of interaction among various factors including drug efflux, DNA damage repair, apoptosis and targets mutation. Long non-coding RNAs (lncRNAs) have been a focus of research in the field of bioscience, and the latest studies have revealed that lncRNAs play essential roles in drug resistance in breast cancer, gastric cancer and lung cancer, et al. Dysregulation of multiple targets and pathways by lncRNAs results in the occurrence of chemoresistance. In this review, we will discuss the mechanisms underlying lncRNA-mediated resistance to chemotherapy and the therapeutic potential of lncRNAs in future cancer treatment.

10 Review Prognostic and Prediction Tools in Bladder Cancer: A Comprehensive Review of the Literature. 2015

Kluth, Luis A / Black, Peter C / Bochner, Bernard H / Catto, James / Lerner, Seth P / Stenzl, Arnulf / Sylvester, Richard / Vickers, Andrew J / Xylinas, Evanguelos / Shariat, Shahrokh F. ·Department of Urology, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY, USA; Department of Urology, University Medical-Center Hamburg-Eppendorf, Hamburg, Germany. · Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada. · Department of Urology, Memorial Sloan-Kettering Cancer Center, Kimmel Center for Prostate and Urologic Tumors, New York, NY, USA. · Academic Urology Unit, University of Sheffield, Sheffield, UK. · Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA. · Department of Urology, Eberhard-Karls University, Tuebingen, Germany. · EORTC Headquarters, Brussels, Belgium. · Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. · Department of Urology, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY, USA; Department of Urology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris Descartes University, Paris, France. · Department of Urology, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY, USA; Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, UT Southwestern, Dallas, TX, USA; Division of Medical Oncology, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY, USA. Electronic address: sfshariat@gmail.com. ·Eur Urol · Pubmed #25709027.

ABSTRACT: CONTEXT: This review focuses on risk assessment and prediction tools for bladder cancer (BCa). OBJECTIVE: To review the current knowledge on risk assessment and prediction tools to enhance clinical decision making and counseling of patients with BCa. EVIDENCE ACQUISITION: A literature search in English was performed using PubMed in July 2013. Relevant risk assessment and prediction tools for BCa were selected. More than 1600 publications were retrieved. Special attention was given to studies that investigated the clinical benefit of a prediction tool. EVIDENCE SYNTHESIS: Most prediction tools for BCa focus on the prediction of disease recurrence and progression in non-muscle-invasive bladder cancer or disease recurrence and survival after radical cystectomy. Although these tools are helpful, recent prediction tools aim to address a specific clinical problem, such as the prediction of organ-confined disease and lymph node metastasis to help identify patients who might benefit from neoadjuvant chemotherapy. Although a large number of prediction tools have been reported in recent years, many of them lack external validation. Few studies have investigated the clinical utility of any given model as measured by its ability to improve clinical decision making. There is a need for novel biomarkers to improve the accuracy and utility of prediction tools for BCa. CONCLUSIONS: Decision tools hold the promise of facilitating the shared decision process, potentially improving clinical outcomes for BCa patients. Prediction models need external validation and assessment of clinical utility before they can be incorporated into routine clinical care. PATIENT SUMMARY: We looked at models that aim to predict outcomes for patients with bladder cancer (BCa). We found a large number of prediction models that hold the promise of facilitating treatment decisions for patients with BCa. However, many models are missing confirmation in a different patient cohort, and only a few studies have tested the clinical utility of any given model as measured by its ability to improve clinical decision making.

11 Review Patients with urinary bladder paragangliomas: a compiled case series from a literature review for clinical management. 2015

Henderson, Sean Jay / Kearns, Patrick J / Tong, Ching Man Carmen / Reddy, Madhumitha / Khurgin, Jacob / Bickell, Michael / Miick, Robert / Ginsberg, Phillip / Metro, Michael J. ·Department of Urology, Albert Einstein Medical Center, Philadelphia, PA. Electronic address: seanjayhenderson@gmail.com. · Department of Biology, Weber State University, Ogden, UT. · Department of Urology, Albert Einstein Medical Center, Philadelphia, PA. · Department of Surgical Pathology, Albert Einstein Medical Center, Philadelphia, PA. ·Urology · Pubmed #25618559.

ABSTRACT: -- No abstract --

12 Review Summary of the 6th Annual Bladder Cancer Think Tank: new directions in urologic research. 2013

Svatek, Robert S / Rosenberg, Jonathan E / Galsky, Matthew D / Lee, Cheryl T / Latini, David M / Bochner, Bernard H / Weizer, Alon Z / Apolo, Andrea B / Sridhar, Srikala S / Kamat, Ashish M / Hansel, Donna / Flaig, Thomas W / Smith, Norm D / Lotan, Yair. ·Department of Urology, UT Health Science Center San Antonio, San Antonio, TX 78229, USA. ·Urol Oncol · Pubmed #22300756.

ABSTRACT: The 6th Annual Bladder Cancer Think Tank brought together a multidisciplinary group of clinicians, researchers, and representatives from the National Cancer Institute and Industry in an effort to advance bladder cancer research efforts. This year's meeting comprised panel discussions and research involving 5 separate working groups, including the Survivorship, Clinical Trials, Standardization of Care, Data Mining, and Translational Science working groups. In this manuscript, the accomplishments and objectives of the working groups are summarized. Notable efforts include: (1) the development of a survivorship care plan for early and late-stage bladder cancer; (2) the development of consensus criteria for eligibility and endpoints for bladder cancer clinical trials; (3) an improved understanding of current practice patterns regarding the use of perioperative chemotherapy in an effort to standardize care; (4) creation of a comprehensive handbook to assist researchers with developing bladder cancer databases; and (5) identification of response to therapy of high-grade non muscle invasive disease through a collaborative exchange of expertise and resources.

13 Review BCG response prediction with cytokine gene variants and bladder cancer: where we are? 2011

Ahirwar, Dinesh Kumar / Manchanda, Parmeet Kaur / Mittal, Rama Devi / Bid, Hemant K. ·Andrology and IVF Laboratories, University of Utah, Salt Lake City, UT 84108, USA. ·J Cancer Res Clin Oncol · Pubmed #21932129.

ABSTRACT: PURPOSE: Bladder cancer (BC) is one of the most widespread cancers afflicting men and women and also has major philosophical impact on health care worldwide. Despite elaborate characterization of the risk factors and treatment options, BC is still a major epidemiological problem worldwide and its incidence lingers to upswing each year. Over the last three decades, intravesical immunotherapy with the biological response modifier Mycobacterium bovis-Bacillus Calmette Guerin (BCG) has been established as the most effective adjuvant treatment for averting local recurrences and tumor progression following transurethral resection of non-muscle-invasive bladder cancer. DESIGN AND METHODS: PUBMED database was searched for articles, and manuscripts were selected that provided data regarding the correlation of BCG therapy and its response with different cytokine gene variants. RESULTS: It is not clear how Bacillus Calmette-Guerin (BCG) works to treat BC. It may stimulate an immune response or cause inflammation of the bladder wall that destroys cancer cells within the bladder. Lot of reports indicated the correlation of various cytokines with respect to BCG therapy in BC, but the exact mechanism is under debate. CONCLUSION: Research continues to establish the most effectual strain of BCG and the best dosage schedule for the treatment for bladder cancer but, on the other hand, a very critical part of this therapy to find out the correlation of different cytokine with BCG therapy, which will give a better insights not only the mechanism but also a better therapeutic options.

14 Review Predictors of outcome of non-muscle-invasive and muscle-invasive bladder cancer. 2011

Youssef, Ramy F / Lotan, Yair. ·Urology Department, UT Southwestern Medical Center, Dallas, Texas, USA. ·ScientificWorldJournal · Pubmed #21336453.

ABSTRACT: Bladder cancer is a major cause of morbidity and mortality. At initial diagnosis, 75% of patients present with non-muscle-invasive disease and 25% of patients have muscle-invasive or metastatic disease.Patients with noninvasive disease suffer from a high rate of recurrence and 10-30% will have disease progression. Patients with muscle-invasive disease are primarily treated with radical cystectomy, but frequently succumb to their disease despite improvements in surgical technique. In non-muscle-invasive disease, multiplicity, tumor size, and prior recurrence rates are the most important predictors for recurrence, while tumor grade, stage, and carcinoma in situ are the most important predictors for progression. The most common tool that clinicians use to predict outcomes after radical cystectomy is still the tumor-node-metastasis (TNM) staging system, with lymph node involvement representing the most important prognostic factor. However, the predictive accuracy of staging and grading systems are limited, and nomograms incorporating clinical and pathologic factors can improve prediction of bladder cancer outcomes. One limitation of current staging is the fact that tumors of a similar stage and grade can have significantly different biology. The integration of molecular markers, especially in a panel approach, has the potential to further improve the accuracy of predictive models and may also identify targets for therapeutic intervention or patients who will respond to systemic therapies.

15 Review Management of bladder cancer: current and emerging strategies. 2009

Agarwal, Neeraj / Hussain, Maha. ·Huntsman Cancer Institute at the University of Utah, Salt Lake City, USA. ·Drugs · Pubmed #19537835.

ABSTRACT: Cancer of the urinary bladder is the fifth most prevalent solid tumour in the US. Urothelial carcinoma is the most common form of bladder cancer, accounting for about 90% of cases. About 25% of patients with bladder cancer have advanced disease (muscle-invasive or metastatic disease) at presentation and are candidates for systemic chemotherapy. Urothelial carcinoma is a chemo-sensitive disease, with a high overall and complete response rate to combination chemotherapy. In the setting of muscle-invasive urothelial carcinoma, use of neoadjuvant chemotherapy is associated with overall survival benefit. The role of adjuvant chemotherapy in this setting is yet to be validated. In the setting of metastatic disease, use of cisplatin-based regimens improves survival. However, despite initial high response rates, the responses are typically not durable leading to recurrence and death in the vast majority of these patients. Currently, there is no standard second-line therapy for patients in whom first-line chemotherapy for metastatic disease has failed. Many newer chemotherapeutic agents have shown modest activity in urothelial carcinoma. Improved understanding of molecular biology and pathogenesis of urothelial carcinoma has opened avenues for the use of molecularly targeted therapies, several of which are being tested in clinical trials. Currently, several novel drugs seem particularly promising including inhibitors of the epidermal growth factor receptor pathway, such as cetuximab, and inhibitors of tumour angiogenesis, such as bevacizumab and sunitinib. Development of reliable molecular predictive markers is expected to improve treatment decisions, therapy development and outcomes in urothelial carcinoma. Funding of and participation in clinical trials are key to advancing the care of urothelial cancer patients. Current and emerging strategies in the medical management of urothelial carcinoma are reviewed.

16 Guideline NCCN Guidelines Insights: Bladder Cancer, Version 2.2016. 2016

Clark, Peter E / Spiess, Philippe E / Agarwal, Neeraj / Bangs, Rick / Boorjian, Stephen A / Buyyounouski, Mark K / Efstathiou, Jason A / Flaig, Thomas W / Friedlander, Terence / Greenberg, Richard E / Guru, Khurshid A / Hahn, Noah / Herr, Harry W / Hoimes, Christopher / Inman, Brant A / Kader, A Karim / Kibel, Adam S / Kuzel, Timothy M / Lele, Subodh M / Meeks, Joshua J / Michalski, Jeff / Montgomery, Jeffrey S / Pagliaro, Lance C / Pal, Sumanta K / Patterson, Anthony / Petrylak, Daniel / Plimack, Elizabeth R / Pohar, Kamal S / Porter, Michael P / Sexton, Wade J / Siefker-Radtke, Arlene O / Sonpavde, Guru / Tward, Jonathan / Wile, Geoffrey / Dwyer, Mary A / Smith, Courtney. ·From Vanderbilt-Ingram Cancer Center; Moffitt Cancer Center; Huntsman Cancer Institute at the University of Utah; Patient Advocate; Mayo Clinic Cancer Center; Stanford Cancer Institute; Massachusetts General Hospital Cancer Center; University of Colorado Cancer Center; UCSF Helen Diller Family Comprehensive Cancer Center; Fox Chase Cancer Center; Roswell Park Cancer Institute; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Memorial Sloan Kettering Cancer Center; Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute; Duke Cancer Institute; UC San Diego Moores Cancer Center; Dana-Farber/Brigham and Women's Cancer Center; Robert H. Lurie Comprehensive Cancer Center of Northwestern University; Fred & Pamela Buffett Cancer Center; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine; University of Michigan Comprehensive Cancer Center; City of Hope Comprehensive Cancer Center; St. Jude Children's Research Hospital/The University of Tennessee Health Science Center; Yale Cancer Center/Smilow Cancer Hospital; The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute; University of Washington/Seattle Cancer Care Alliance; The University of Texas MD Anderson Cancer Center; University of Alabama at Birmingham Comprehensive Cancer Center; and National Comprehensive Cancer Network. ·J Natl Compr Canc Netw · Pubmed #27697976.

ABSTRACT: These NCCN Guidelines Insights discuss the major recent updates to the NCCN Guidelines for Bladder Cancer based on the review of the evidence in conjunction with the expert opinion of the panel. Recent updates include (1) refining the recommendation of intravesical bacillus Calmette-Guérin, (2) strengthening the recommendations for perioperative systemic chemotherapy, and (3) incorporating immunotherapy into second-line therapy for locally advanced or metastatic disease. These NCCN Guidelines Insights further discuss factors that affect integration of these recommendations into clinical practice.

17 Clinical Trial Background and Update for S1602 "A Phase III Randomized Trial to Evaluate the Influence of BCG Strain Differences and T Cell Priming with Intradermal BCG Before Intravesical Therapy for BCG-naïve High-grade Non-muscle-invasive Bladder Cancer. 2018

Svatek, Robert S / Tangen, Cathy / Delacroix, Scott / Lowrance, William / Lerner, Seth P. ·Department of Urology, University of Texas Health San Antonio, San Antonio, TX, USA. Electronic address: svatek@uthscsa.edu. · SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. · Louisiana State University, Department of Urology and Gulf South NCORP, New Orleans, LA, USA. · Department of Urology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA. · Scott Department of Urology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA. ·Eur Urol Focus · Pubmed #30197040.

ABSTRACT: The S1602 Intergroup trial is a randomized phase III clinical trial that aims to test two important hypotheses: (1) priming with intradermal bacillus Calmette-Guérin (BCG) vaccine prior to standard intravesical BCG improves response to BCG in terms of recurrence-free survival and (2) Tokyo-172 BCG strain is non-inferior to TICE BCG in terms of time to high-grade recurrence. The study was approved by the Cancer Therapy Evaluation Program of the National Cancer Institute and activated in spring 2017. Here, we provide a synopsis of the study background, design, and update of the clinical trial.

18 Clinical Trial A Phase 1/2 Trial of a Combination of Paclitaxel and Trastuzumab With Daily Irradiation or Paclitaxel Alone With Daily Irradiation After Transurethral Surgery for Noncystectomy Candidates With Muscle-Invasive Bladder Cancer (Trial NRG Oncology RTOG 0524). 2017

Michaelson, M Dror / Hu, Chen / Pham, Huong T / Dahl, Douglas M / Lee-Wu, Chin / Swanson, Gregory P / Vuky, Jacqueline / Lee, R Jeffrey / Souhami, Luis / Chang, Brian / George, Asha / Sandler, Howard / Shipley, William. ·Massachusetts General Hospital Cancer Center, Boston, Massachusetts. Electronic address: dmichaelson1@partners.org. · NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania; Sydney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Virginia Mason CCOP, Seattle, Washington. · Massachusetts General Hospital Cancer Center, Boston, Massachusetts. · University of Texas at San Antonio, San Antonio, Texas. · Intermountain Medical Center, Murray, Utah. · McGill University, Montréal, Quebec. · Parkview Cancer Center, Parkview Hospital, Fort Wayne, Indiana. · NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania. · Cedars-Sinai Medical Center, Los Angeles, California. ·Int J Radiat Oncol Biol Phys · Pubmed #28333021.

ABSTRACT: PURPOSE: Bladder preservation therapy is an effective treatment for muscle-invasive urothelial carcinoma (UC). In this study we treated noncystectomy candidates with daily radiation and weekly paclitaxel for 7 weeks. Patients whose tumors showed her2/neu overexpression were additionally treated with weekly trastuzumab. METHODS AND MATERIALS: Sixty-eight evaluable patients were treated with radiation therapy and either paclitaxel + trastuzumab (group 1) or paclitaxel alone (group 2). Groups were assigned on the basis of her2/neu immunohistochemistry results. Patients received 1.8-Gy fractions to a total dose of 64.8 Gy. The primary endpoint of the study was treatment-related toxicity, and secondary endpoints included complete response (CR) rate, protocol completion rate, and survival. RESULTS: A total of 20 evaluable patients were treated in group 1 and 46 patients in group 2. Acute treatment-related adverse events (AEs) were observed in 7 of 20 patients in group 1 (35%) and 14 of 46 patients in group 2 (30.4%). Protocol therapy was completed by 60% (group 1) and 74% (group 2) of patients. Most incompletions were due to toxicity, and the majority of AEs were gastrointestinal, including 1 grade 5 AE (group 1). Two other deaths (both in group 2) were unrelated to protocol therapy. No unexpected cardiac, hematologic, or other toxicities were observed. The CR rate at 1 year was 72% for group 1 and 68% for group 2. CONCLUSIONS: In patients with muscle-invasive UC who are not candidates for cystectomy, daily radiation combined with paclitaxel is an effective treatment strategy with a high completion rate and moderate toxicity. In patients with her2/neu-positive tumors, a group generally considered to have worse outcomes, the addition of trastuzumab appears to result in comparable efficacy and toxicity. Further biomarker-driven trials should be undertaken in advancing treatment of this challenging disease.

19 Clinical Trial Safety and Efficacy of Durvalumab (MEDI4736), an Anti-Programmed Cell Death Ligand-1 Immune Checkpoint Inhibitor, in Patients With Advanced Urothelial Bladder Cancer. 2016

Massard, Christophe / Gordon, Michael S / Sharma, Sunil / Rafii, Saeed / Wainberg, Zev A / Luke, Jason / Curiel, Tyler J / Colon-Otero, Gerardo / Hamid, Omid / Sanborn, Rachel E / O'Donnell, Peter H / Drakaki, Alexandra / Tan, Winston / Kurland, John F / Rebelatto, Marlon C / Jin, Xiaoping / Blake-Haskins, John A / Gupta, Ashok / Segal, Neil H. ·Christophe Massard, Institut Gustave Roussy Cancer Centre, Villejuif, France · Michael S. Gordon, Pinnacle Oncology Hematology, Scottsdale, AZ · Sunil Sharma, Huntsman Cancer Institute, Salt Lake City, UT · Saeed Rafii, Sarah Cannon Research Institute, London, UK · Zev A. Wainberg and Alexandra Drakaki, University of California, Los Angeles · and Omid Hamid, The Angeles Clinic and Research Institute, Los Angeles, CA · Jason Luke and Peter H. O'Donnell, University of Chicago Comprehensive Cancer Center, Chicago, IL · Tyler J. Curiel, The University of Texas Health Science Center, San Antonio, TX · Gerardo Colon-Otero and Winston Tan, Mayo Clinic, Jacksonville, FL · Rachel E. Sanborn, Providence Cancer Center, Portland, OR · John F. Kurland, Marlon C. Rebelatto, Xiaoping Jin, John A. Blake-Haskins, and Ashok Gupta, MedImmune, Gaithersburg, MD · and Neil H. Segal, Memorial Sloan Kettering Cancer Center, New York, NY. ·J Clin Oncol · Pubmed #27269937.

ABSTRACT: PURPOSE: To investigate the safety and efficacy of durvalumab, a human monoclonal antibody that binds programmed cell death ligand-1 (PD-L1), and the role of PD-L1 expression on clinical response in patients with advanced urothelial bladder cancer (UBC). METHODS: A phase 1/2 multicenter, open-label study is being conducted in patients with inoperable or metastatic solid tumors. We report here the results from the UBC expansion cohort. Durvalumab (MEDI4736, 10 mg/kg every 2 weeks) was administered intravenously for up to 12 months. The primary end point was safety, and objective response rate (ORR, confirmed) was a key secondary end point. An exploratory analysis of pretreatment tumor biopsies led to defining PD-L1-positive as ≥ 25% of tumor cells or tumor-infiltrating immune cells expressing membrane PD-L1. RESULTS: A total of 61 patients (40 PD-L1-positive, 21 PD-L1-negative), 93.4% of whom received one or more prior therapies for advanced disease, were treated (median duration of follow-up, 4.3 months). The most common treatment-related adverse events (AEs) of any grade were fatigue (13.1%), diarrhea (9.8%), and decreased appetite (8.2%). Grade 3 treatment-related AEs occurred in three patients (4.9%); there were no treatment-related grade 4 or 5 AEs. One treatment-related AE (acute kidney injury) resulted in treatment discontinuation. The ORR was 31.0% (95% CI, 17.6 to 47.1) in 42 response-evaluable patients, 46.4% (95% CI, 27.5 to 66.1) in the PD-L1-positive subgroup, and 0% (95% CI, 0.0 to 23.2) in the PD-L1-negative subgroup. Responses are ongoing in 12 of 13 responding patients, with median duration of response not yet reached (range, 4.1+ to 49.3+ weeks). CONCLUSION: Durvalumab demonstrated a manageable safety profile and evidence of meaningful clinical activity in PD-L1-positive patients with UBC, many of whom were heavily pretreated.

20 Article Geographic Variation in Cystoscopy Rates for Suspected Bladder Cancer between Female and Male Medicare Beneficiaries. 2018

Han, David S / Zhou, Weiping / Seigne, John D / Lynch, Kristine E / Schroeck, Florian R. ·The Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine at Dartmouth, Lebanon, NH. · Section of Urology, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH. · VA Salt Lake City Health Care System and the Division of Epidemiology, University of Utah, Salt Lake City, UT. · The Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine at Dartmouth, Lebanon, NH; Section of Urology, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH; The White River Junction VA Medical Center, White River Junction, VT. Electronic address: florian.r.schroeck@dartmouth.edu. ·Urology · Pubmed #30138684.

ABSTRACT: OBJECTIVE: To assess geographic variation in cystoscopy rates among women vs men with suspected bladder cancer, lending insight into gender-specific differences in cystoscopic evaluation. METHODS: We conducted a cross-sectional study of all fee-for-service Medicare beneficiaries within 306 Hospital Referral Regions (HRRs) who received care in 2014. For each HRR, we calculated the age- and race-adjusted cystoscopy rate for women and men as our primary outcome. The rate was the number of beneficiaries who underwent cystoscopy for bladder cancer symptoms (using procedure and ICD-9 diagnosis codes) divided by all beneficiaries in the HRR. We used the coefficient of variation to compare relative variability of cystoscopy rates. RESULTS: Overall, 173,551 women (n = 14.8 million) and 286,090 men (n = 11.5 million) underwent cystoscopy in 2014. While women received less cystoscopies compared to men (mean 11.0 vs 23.5 per 1000, P < .001), there was greater variation in cystoscopy rates among women (coefficient of variation 27.5 vs 23.5, P = .010). When restricting to ICD-9 codes for hematuria only, women continued to demonstrate greater variation in cystoscopy rates (coefficient of variation 27.8 vs 24.2, P = .022). Findings were robust across larger HRR sizes-thereby removing some random variation seen in smaller HRRs-as well as across years 2010, 2011, 2012, and 2013. CONCLUSION: Cystoscopy rates are lower in women than men, likely due to their lower bladder cancer incidence. However, there is greater variation in cystoscopy rates among women with symptoms of bladder cancer. This may reflect increased provider uncertainty whether to refer and work-up women with suspected bladder cancer.

21 Article Pathological characteristics and prognostic indicators of different histopathological types of urinary bladder cancer following radical cystectomy in a large single-center Egyptian cohort. 2018

Martin, Jeremy W / Vernez, Simone L / Lotan, Yair / Abdelhalim, Ahmed / Dutta, Rahul / Shokeir, Ahmed / Abol-Enein, Hassan / Mosbah, Ahmed / Ghoneim, Mohamed / Youssef, Ramy F. ·Department of Urology, University of California, Irvine, Orange, CA, USA. · Department of Urology, UT Southwestern Medical Center, Dallas, TX, USA. · Department of Urology, Urology and Nephrology Center, Mansoura, Egypt. · Department of Urology, University of California, Irvine, Orange, CA, USA. ryaacoub@uci.edu. ·World J Urol · Pubmed #29761225.

ABSTRACT: OBJECTIVE: To evaluate differences in pathological features and prognostics across four bladder cancer histopathological types: urothelial carcinoma (UC), urothelial carcinoma with variant histology (UCV), squamous cell carcinoma (SCC) and adenocarcinoma (ADC), utilizing a large cohort of radical cystectomy (RC) patients. METHODS: A retrospective analysis of patients who underwent RC at a single institution in Egypt between 1997 and 2004 was performed. Kaplan-Meier and multivariable analyses were performed to evaluate the prognostic significance of pathological features including tumor stage, grade, lymphovascular invasion (LVI), and lymph node (LN) involvement in the different subtypes on disease-free survival (DFS). RESULTS: 1238 patients (975 male, 263 female) were included, of whom 577 (47%) had UC, 174 (14%) UCV, 398 (32%) SCC, and 89 (7%) ADC. Median age was 54 (20-87) years and median follow-up was 40 months (0-110). There were significant differences in stage, grade, LVI, LN involvement, and presence of schistosomiasis across the subtypes (all p < 0.05). The prognostic significance of LVI was more evident in SCC (HR 2.14, p = 0.003) and ADC (HR 2.17, p = 0.044) than in UC (HR 1.66, p = 0.008). LN involvement was the strongest prognostic factor in UCV (HR 2.14, p = 0.012). CONCLUSIONS: There are significant differences in clinicopathological features and their prognostic impact across bladder cancer subtypes. The prognostic significance of LVI is more evident in SCC and ADC, while LN involvement is more prognostic in UCV. Determining independent predictors in individual subtypes can guide multimodal treatment selection and clinical trial design.

22 Article CAS-viewer: web-based tool for splicing-guided integrative analysis of multi-omics cancer data. 2018

Han, Seonggyun / Kim, Dongwook / Kim, Youngjun / Choi, Kanghoon / Miller, Jason E / Kim, Dokyoon / Lee, Younghee. ·Department of Biomedical Informatics, University of Utah, University of Utah School of Medicine, Salt Lake City, UT, 84108, USA. · University of Utah, School of Computing, University of Utah, Salt Lake City, UT, 84108, USA. · Department of Biomedical & Translational Informatics, Geisinger Health System, Danville, PA, 17822, USA. · The Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, 16082, USA. · Department of Biomedical Informatics, University of Utah, University of Utah School of Medicine, Salt Lake City, UT, 84108, USA. younghee.lee@utah.edu. ·BMC Med Genomics · Pubmed #29697367.

ABSTRACT: BACKGROUND: The Cancer Genome Atlas (TCGA) project is a public resource that provides transcriptomic, DNA sequence, methylation, and clinical data for 33 cancer types. Transforming the large size and high complexity of TCGA cancer genome data into integrated knowledge can be useful to promote cancer research. Alternative splicing (AS) is a key regulatory mechanism of genes in human cancer development and in the interaction with epigenetic factors. Therefore, AS-guided integration of existing TCGA data sets will make it easier to gain insight into the genetic architecture of cancer risk and related outcomes. There are already existing tools analyzing and visualizing alternative mRNA splicing patterns for large-scale RNA-seq experiments. However, these existing web-based tools are limited to the analysis of individual TCGA data sets at a time, such as only transcriptomic information. RESULTS: We implemented CAS-viewer (integrative analysis of Cancer genome data based on Alternative Splicing), a web-based tool leveraging multi-cancer omics data from TCGA. It illustrates alternative mRNA splicing patterns along with methylation, miRNAs, and SNPs, and then provides an analysis tool to link differential transcript expression ratio to methylation, miRNA, and splicing regulatory elements for 33 cancer types. Moreover, one can analyze AS patterns with clinical data to identify potential transcripts associated with different survival outcome for each cancer. CONCLUSIONS: CAS-viewer is a web-based application for transcript isoform-driven integration of multi-omics data in multiple cancer types and will aid in the visualization and possible discovery of biomarkers for cancer by integrating multi-omics data from TCGA.

23 Article The effects of alternative splicing on miRNA binding sites in bladder cancer. 2018

Han, Seonggyun / Kim, Dongwook / Shivakumar, Manu / Lee, Young-Ji / Garg, Tullika / Miller, Jason E / Kim, Ju Han / Kim, Dokyoon / Lee, Younghee. ·Department of Biomedical Informatics, University of Utah School of Medicine, Salt Lake City, Utah, United States of America. · Department of Biomedical & Translational Informatics, Geisinger Health System, Danville, Pennsylvania, United States of America. · Department of Biomedical Informatics, School of Nursing, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America. · Mowad Urology Department, Geisinger Health System, Danville, Pennsylvania, United States of America. · Seoul National University Biomedical Informatics, Seoul, South Korea. ·PLoS One · Pubmed #29300757.

ABSTRACT: Eukaryotic organisms have developed a variety of mechanisms to regulate translation post-transcriptionally, including but not limited to the use of miRNA silencing in many species. One method of post-transcriptional regulation is through miRNAs that bind to the 3' UTRs to regulate mRNA abundance and influence protein expression. Therefore, the diversity of mRNA 3' UTRs mediating miRNA binding sites influence miRNA-mediated regulation. Alternative polyadenylation, by shortening mRNA isoforms, increases the diversity of 3' UTRs; moreover, short mRNA isoforms elude miRNA-medicated repression. Because no current prediction methods for putative miRNA target sites consider whether or not 1) splicing-informed miRNA binding sites and/or 2) the use of 3' UTRs provide higher resolution or functionality, we sought to identify not only the genome-wide impact of using exons in mRNA 3' UTRs but also their functional connection to miRNA regulation and clinical outcomes in cancer. With a genome-wide expression of mRNA and miRNA quantified by 395 bladder cancer cases from The Cancer Genome Atlas (TCGA), we 1) demonstrate the diversity of 3' UTRs affecting miRNA efficiency and 2) identify a set of genes clinically associated with mRNA expression in bladder cancer. Knowledge of 3' UTR diversity will not only be a useful addition to current miRNA target prediction algorithms but also enhance the clinical utility of mRNA isoforms in the expression of mRNA in cancer. Thus, variability among cancer patient's variability in molecular signatures based on these exon usage events in 3' UTR along with miRNAs in bladder cancer may lead to better prognostic/treatment strategies for improved precision medicine.

24 Article Comprehensive Genomic Sequencing of Urothelial Tumors Identifies Rare SMARCB1 (INI-1)-Deficient Carcinomas of the Urinary System. 2018

Gupta, Sumati / Albertson, Daniel / Gaston, David / Heilbrun, Marta E / Agarwal, Neeraj / Boucher, Ken / Parnell, Timothy J / Liu, Ting / Morgans, Alicia / Madison, Russell / Gowen, Kyle / Miller, Vincent A / Ross, Jeffrey S / Ali, Siraj M / Millis, Sherri Z. ·Huntsman Cancer Institute, University of Utah, Salt Lake City, UT. Electronic address: sumati.gupta@hci.utah.edu. · Department of Pathology and Associated Regional and University Pathologists Laboratories, University of Utah, Salt Lake City, UT. · School of Medicine, University of Utah, Salt Lake City, UT. · Department of Radiology, University of Utah, Salt Lake City, UT. · Huntsman Cancer Institute, University of Utah, Salt Lake City, UT. · Vanderbilt University, Nashville, TN. · Foundation Medicine Inc, Cambridge, MA. · Foundation Medicine Inc, Cambridge, MA; Albany Medical College, Albany, NY. ·Clin Genitourin Cancer · Pubmed #28974397.

ABSTRACT: PURPOSE: Tumor genomic profiling helps direct therapy for advanced urothelial carcinoma (UC). In the course of clinical care, we encountered a patient with a complete loss of SMARCB1 (switch/sucrose nonfermentable-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1), which encodes INI-1 (integrase interactor 1), as the sole detected driver of their urinary tract tumor. Our objective was the identification and genomic characterization of urinary tract neoplasia with complete SMARCB1 loss. PATIENTS AND METHODS: Tissue from 1287 patients with UC was assayed by hybrid capture-based comprehensive genomic profiling (CGP) in the course of clinical care to evaluate genomic alterations (GA), such as, base substitutions, insertions/deletions, amplifications, copy number alterations, fusions/rearrangements, and targeted therapy opportunities. A total of 315 genes frequently altered in cancer were assayed. RESULTS: CGP identified 10 patients with SMARCB1 alterations. Of the 10 patients, 4 (1 each with renal pelvis, ureter, bladder, and unknown primary cancer) had complete loss of SMARCB1, and 6 had loss of heterozygosity with an unknown effect on function or heterozygous loss. Patients with complete SMARCB1 loss had few or no additional alterations. Compared with conventional UC, the tumor mutational burden was significantly lower (P = .004). All 4 patients with complete SMARCB1-loss tumors were < 56 years old and 3 were female. CONCLUSION: The genomic profiles of the tumors from patients with UC revealed a population of tumors driven by complete loss of SMARCB1. This previously uncharacterized subset of INI-1-deficient urinary tract tumors might constitute a new tumor category that could be sensitive to targeted therapy, including EZH2 (enhancer of zeste homolog 2) inhibition. Clinical trial testing could be challenging owing to the rarity of the disease.

25 Article Robot-assisted Versus Open Radical Cystectomy in Patients Receiving Perioperative Chemotherapy for Muscle-invasive Bladder Cancer: The Oncologist's Perspective from a Multicentre Study. 2018

Necchi, Andrea / Pond, Gregory R / Smaldone, Marc C / Pal, Sumanta K / Chan, Kevin / Wong, Yu-Ning / Viterbo, Rosalia / Sonpavde, Guru / Harshman, Lauren C / Crabb, Simon / Alva, Ajjai / Chowdhury, Simon / De Giorgi, Ugo / Srinivas, Sandy / Agarwal, Neeraj / Bamias, Aristotelis / Baniel, Jack / Golshayan, Ali-Reza / Ladoire, Sylvain / Sternberg, Cora N / Cerbone, Linda / Yu, Evan Y / Bellmunt, Joaquim / Vaishampayan, Ulka / Niegisch, Gunter / Hussain, Syed / Bowles, Daniel W / Morales-Barrera, Rafael / Milowsky, Matthew I / Theodore, Christine / Berthold, Dominik R / Sridhar, Srikala S / Powles, Thomas / Rosenberg, Jonathan E / Galsky, Matthew D / Anonymous1221193. ·Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: andrea.necchi@istitutotumori.mi.it. · McMaster University, Hamilton, Ontario, Canada. · Fox Chase Cancer Center, Philadelphia, PA, USA. · City of Hope Comprehensive Cancer Center, Duarte, CA, USA. · UAB Comprehensive Cancer Center, Birmingham, AL, USA. · Dana Farber Cancer Institute, Boston, MA, USA. · University of Southampton, Southampton, UK. · University of Michigan, Ann Arbor, MI, USA. · Guy's and St. Thomas' Hospital, London, UK. · IRCCS Istituto Scientifico Romagnolo per lo studio e la Cura dei Tumori, Meldola, Italy. · Stanford University School of Medicine, Stanford, CA, USA. · University of Utah, Salt Lake City, UT, USA. · University of Athens, Athens, Greece. · Rabin Medical Center, Petach Tikva, Israel. · Medical University of South Carolina, Charleston, SC, USA. · Centre Georges-François Leclerc, Dijon, France. · San Camillo Forlanini Hospital, Rome, Italy. · University of Washington, Seattle, WA, USA. · Karmanos Cancer Institute, Detroit, MI, USA. · Heinrich-Heine-University, Düsseldorf, Germany. · University of Liverpool, Liverpool, UK. · Denver Veterans Affairs Medical Center, Eastern Colorado Health Care System, Denver, CO, USA. · Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Universitat Autonoma de Barcelona, Barcelona, Spain. · University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, NC, USA. · Hopital Foch, Suresnes, France. · Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. · Princess Margaret Hospital, University Health Network, Toronto, Canada. · Barts Health and the Royal Free NHS Trust, Queen Mary University of London, London, UK. · Memorial Sloan-Kettering Cancer Center, New York, NY, USA. · Mount Sinai School of Medicine, Tisch Cancer Institute, New York, NY, USA. ·Eur Urol Focus · Pubmed #28753879.

ABSTRACT: BACKGROUND: Little is known about the outcomes of robot-assisted radical cystectomy (RARC) compared to open radical cystectomy (ORC) combined with perioperative chemotherapy for muscle-invasive urothelial bladder cancer (UBC). OBJECTIVE: To evaluate surgical and oncological outcomes for RARC and ORC in multimodal treatment. DESIGN, SETTING, AND PARTICIPANTS: Data from 28 centres were collected for cystectomies performed between January 2000 and July 2013. INTERVENTION: RARC or ORC combined with perioperative chemotherapy for UBC. OUTCOME MEASURES AND STATISTICAL ANALYSIS: Fisher's exact tests, χ RESULTS AND LIMITATIONS: A total of 688 patients (n=603 ORC and n=85 RARC) were analysed; 60.6% received neoadjuvant chemotherapy, and 45.1% adjuvant chemotherapy. No significant differences in baseline characteristics were found between the groups. The median time from surgery to adjuvant chemotherapy was 1.9 mo for both RARC and ORC groups. The median number of lymph nodes removed was 21 (interquartile range [IQR] 14-35) for RARC and 13 (IQR 8-21) for ORC (p<0.001); the results were confirmed in subgroup analyses. Multivariable analyses revealed no difference in the rate of positive surgical margins (p=0.54 and p=0.78), rate of neobladder diversion (p=0.33 and p=0.51), relapse-free survival (p=0.31 and p=0.23), and overall survival (p=0.63 and p=0.69). The retrospective nature of the data is the major limitation. CONCLUSIONS: In this study, no differences in efficacy outcomes or ability to deliver adjuvant chemotherapy were observed between RARC and ORC. The increasing use of RARC is justifiable from an oncological viewpoint. PATIENT SUMMARY: In a retrospective study of patients who received perioperative chemotherapy for urothelial bladder cancer, we found no difference in key outcomes between robot-assisted radical cystectomy (RARC) and open radical cystectomy. Performing RARC seems to be justifiable in the multidisciplinary setting.