Treatment of Non‐Metastatic Muscle‐Invasive Bladder Cancer: AUA/ASCO/ASTRO/SUO Guideline

Purpose: This multidisciplinary, evidence‐based guideline for clinically non‐metastatic muscle‐invasive bladder cancer focuses on the evaluation, treatment and surveillance of muscle‐invasive bladder cancer guided toward curative intent. Materials and Methods: A systematic review utilizing research from the Agency for Healthcare Research and Quality as well as additional supplementation by the authors and consultant methodologists was used to develop the guideline. Evidence‐based statements were based on body of evidence strengths Grade A, B or C and were designated as Strong, Moderate and Conditional Recommendations with additional statements presented in the form of Clinical Principles or Expert Opinions. Results: For the first time for any type of malignancy, the American Urological Association, American Society of Clinical Oncology, American Society for Radiation Oncology and Society of Urologic Oncology have formulated an evidence‐based guideline based on a risk‐stratified clinical framework for the management of muscle‐invasive urothelial bladder cancer. This document is designed to be used in conjunction with the associated treatment algorithm. Conclusions: The intensity and scope of care for muscle‐invasive bladder cancer should focus on the patient, disease and treatment response characteristics. This guideline attempts to improve a clinician's ability to evaluate and treat each patient, but higher quality evidence in future trials will be essential to improve level of care for these patients.

[1]  O. S. Nielsen,et al.  Neoadjuvant Chemotherapy with Cisplatin and Methotrexate in Patients with Muscle-Invasive Bladder Tumours , 2002, Acta oncologica.

[2]  I. Tannock,et al.  Improved local control of invasive bladder cancer by concurrent cisplatin and preoperative or definitive radiation. The National Cancer Institute of Canada Clinical Trials Group. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  T. Kessler,et al.  Nerve-sparing radical cystectomy and orthotopic bladder replacement in female patients. , 2007, European urology.

[4]  A. Kibel,et al.  Radiotherapy with or Without Chemotherapy in Muscle-Invasive Bladder Cancer , 2012 .

[5]  R. Kuefer,et al.  Upper urinary tract recurrence after radical cystectomy for bladder cancer--who is at risk? , 2009, The Journal of urology.

[6]  Sam S. Chang,et al.  Lymph node yield at radical cystectomy predicts mortality in node-negative and not node-positive patients. , 2012, Urology.

[7]  J. McKiernan,et al.  The role of preoperative prostatic urethral biopsy in clinical decision-making at the time of radical cystectomy. , 2013, The Canadian journal of urology.

[8]  J. Cheville,et al.  Outcomes following radical cystectomy for micropapillary bladder cancer versus pure urothelial carcinoma: a matched cohort analysis , 2012, World Journal of Urology.

[9]  T. Powles,et al.  Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle‐invasive bladder cancer , 2015, Cancer.

[10]  S. Fosså,et al.  Clinical significance of routine pre-cystectomy bone scans in patients with muscle-invasive bladder cancer. , 1996, British journal of urology.

[11]  F. Guillemin,et al.  Combined surgery and brachytherapy in the treatment of some cancers of the bladder (partial cystectomy and interstitial iridium-192). , 1996, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[12]  C. Dinney,et al.  Risk of urethral, vaginal and cervical involvement in patients undergoing radical cystectomy for bladder cancer: results of a contemporary cystectomy series from M. D. Anderson Cancer Center. , 1997, The Journal of urology.

[13]  T. Ten Have,et al.  Radical cystectomy versus bladder-preserving therapy for muscle-invasive urothelial carcinoma: examining confounding and misclassification biasin cancer observational comparative effectiveness research. , 2013, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[14]  A. Sagalowsky,et al.  The diagnosis and treatment of urethral recurrence after radical cystectomy. , 2006, Urologic oncology.

[15]  L. Kiemeney,et al.  Epidemiology and risk factors of urothelial bladder cancer. , 2013, European urology.

[16]  T. H. van der Kwast,et al.  A contemporary update on pathology standards for bladder cancer: transurethral resection and radical cystectomy specimens. , 2013, European urology.

[17]  S. Phillips,et al.  The relationship between perioperative blood transfusion and overall mortality in patients undergoing radical cystectomy for bladder cancer. , 2013, Urologic oncology.

[18]  Y. Uekado,et al.  Adjuvant chemotherapy for invasive bladder cancer , 2004, Cancer Chemotherapy and Pharmacology.

[19]  D. Silverman,et al.  Association between smoking and risk of bladder cancer among men and women. , 2011, JAMA.

[20]  J. Coebergh,et al.  Effects of age and comorbidity on treatment and survival of patients with muscle‐invasive bladder cancer , 2014, International journal of cancer.

[21]  W. Duncan,et al.  The results of a series of 963 patients with transitional cell carcinoma of the urinary bladder primarily treated by radical megavoltage X-ray therapy. , 1986, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[22]  Sam S. Chang,et al.  Alvimopan accelerates gastrointestinal recovery after radical cystectomy: a multicenter randomized placebo-controlled trial. , 2014, European urology.

[23]  R. Hautmann,et al.  The ileal neobladder in women: 9 years of experience with 18 patients. , 1996, The Journal of urology.

[24]  H. Salem,et al.  Primary and secondary malignant involvement of gynaecological organs at radical cystectomy for bladder cancer: Review of literature and retrospective analysis of 360 cases , 2012, Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology.

[25]  Sanjay G. Patel,et al.  Early and late perioperative outcomes following radical cystectomy: 90-day readmissions, morbidity and mortality in a contemporary series. , 2010, The Journal of urology.

[26]  M. Wirth,et al.  Relationship of the number of removed lymph nodes to bladder cancer and competing mortality after radical cystectomy. , 2014, European urology.

[27]  David C. Smith,et al.  Efficient delivery of radical cystectomy after neoadjuvant chemotherapy for muscle‐invasive bladder cancer , 2012, Cancer.

[28]  J. Gore,et al.  Impact of a bladder cancer diagnosis on smoking behavior. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  J. Cheville,et al.  Long‐term results of radical cystectomy and role of adjuvant chemotherapy for small cell carcinoma of the bladder , 2015, International journal of urology : official journal of the Japanese Urological Association.

[30]  J. Montie,et al.  Prostate capsule sparing versus nerve sparing radical cystectomy for bladder cancer: results of a randomized, controlled trial. , 2015, The Journal of urology.

[31]  N. Malats,et al.  Occupation and bladder cancer in a hospital-based case–control study in Spain , 2007, Occupational and Environmental Medicine.

[32]  A. Kotb,et al.  Safety of no bowel preparation before ileal urinary diversion , 2012, BJU International.

[33]  Katherine A. Hoadley,et al.  Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology , 2014, Proceedings of the National Academy of Sciences.

[34]  Ronald C Chen,et al.  Muscle‐invasive bladder cancer: evaluating treatment and survival in the National Cancer Data Base , 2014, BJU international.

[35]  A. Imai,et al.  Neoadjuvant gemcitabine and carboplatin followed by immediate cystectomy may be associated with a survival benefit in patients with clinical T2 bladder cancer , 2014, Medical Oncology.

[36]  D. Penson,et al.  Urinary functional outcome following radical cystoprostatectomy and ileal neobladder reconstruction in male patients. , 2013, The Journal of urology.

[37]  Sunil V. Rao,et al.  Red Blood Cell Transfusion: A Clinical Practice Guideline From the AABB* , 2012, Annals of Internal Medicine.

[38]  P. Nietert,et al.  Evaluation of urovysion and cytology for bladder cancer detection , 2013, Cancer cytopathology.

[39]  K. Baggerly,et al.  Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. , 2014, Cancer cell.

[40]  A. Vickers,et al.  Standardization of pelvic lymphadenectomy performed at radical cystectomy , 2006, Cancer.

[41]  A. Niemierko,et al.  Long-term outcomes of selective bladder preservation by combined-modality therapy for invasive bladder cancer: the MGH experience. , 2012, European urology.

[42]  B. Bochner,et al.  Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. , 2009, European urology.

[43]  M. Zelefsky,et al.  External beam radiation therapy for small cell carcinoma of the urinary bladder. , 2015, Practical radiation oncology.

[44]  Tony Fletcher,et al.  Sequence variant on 8q24 confers susceptibility to urinary bladder cancer , 2008, Nature Genetics.

[45]  J. Cheville,et al.  Sarcopenia in patients with bladder cancer undergoing radical cystectomy: Impact on cancer‐specific and all‐cause mortality , 2014, Cancer.

[46]  A. Vickers,et al.  Longitudinal risk of upper tract recurrence following radical cystectomy for urothelial cancer and the potential implications for long-term surveillance. , 2008, The Journal of urology.

[47]  K. Steven,et al.  Radical cystectomy: extending the limits of pelvic lymph node dissection improves survival for patients with bladder cancer confined to the bladder wall. , 1998, The Journal of urology.

[48]  R. Cowan,et al.  Phase II study of conformal hypofractionated radiotherapy with concurrent gemcitabine in muscle-invasive bladder cancer. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[49]  P. Dasgupta,et al.  Enhanced Recovery After Robot-assisted Radical Cystectomy: EAU Robotic Urology Section Scientific Working Group Consensus View. , 2016, European urology.

[50]  V. Reuter,et al.  Impact of the number of lymph nodes retrieved on outcome in patients with muscle invasive bladder cancer. , 2003, The Journal of urology.

[51]  J. Stein,et al.  Upper tract urothelial recurrence following radical cystectomy for transitional cell carcinoma of the bladder: an analysis of 1,069 patients with 10-year followup. , 2007, The Journal of urology.

[52]  Peter Clark,et al.  Contemporary management of the urethra in patients after radical cystectomy for bladder cancer. , 2005, The Urologic clinics of North America.

[53]  P. Pierorazio,et al.  Causes, Timing, Hospital Costs and Perioperative Outcomes of Index vs Nonindex Hospital Readmissions after Radical Cystectomy: Implications for Regionalization of Care , 2017, The Journal of urology.

[54]  F. Saad,et al.  Partial cystectomy does not undermine cancer control in appropriately selected patients with urothelial carcinoma of the bladder: a population-based matched analysist. , 2009, Urology.

[55]  P. Kantoff,et al.  Neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin with pegfilgrastim support in muscle-invasive urothelial cancer: pathologic, radiologic, and biomarker correlates. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[56]  Yair Lotan,et al.  Nomogram for predicting disease recurrence after radical cystectomy for transitional cell carcinoma of the bladder. , 2006, The Journal of urology.

[57]  J. Smith Urethral recurrence after cystoprostatectomy: implications for urinary diversion and monitoring. , 2005, The Journal of urology.

[58]  G. Muto,et al.  Stage‐specific impact of extended versus standard pelvic lymph node dissection in radical cystectomy , 2013, International journal of urology : official journal of the Japanese Urological Association.

[59]  W. Murphy,et al.  Urethral wash cytopathology for monitoring patients after cystoprostatectomy with urinary diversion , 2003, Cancer.

[60]  M. Faraday,et al.  Staying at the cutting edge: a review and analysis of evidence reporting and grading; the recommendations of the American Urological Association , 2009, BJU international.

[61]  T. Dorff,et al.  Neoadjuvant chemotherapy with gemcitabine/cisplatin vs. methotrexate/vinblastine/doxorubicin/cisplatin for muscle-invasive urothelial carcinoma of the bladder: a retrospective analysis from the University of Southern California. , 2013, Urologic oncology.

[62]  S. Daneshmand,et al.  A critical analysis of perioperative mortality from radical cystectomy. , 2006, The Journal of urology.

[63]  A. Goussia,et al.  Radical therapy for muscle-infiltrating bladder cancer (cystectomy or radiotherapy): does age affect the final therapeutic benefit for the patient? , 2008, Journal of B.U.ON. : official journal of the Balkan Union of Oncology.

[64]  S. Shariat,et al.  Stage specific lymph node metastasis mapping in radical cystectomy specimens. , 2004, The Journal of urology.

[65]  A. Vickers,et al.  Natural history of positive urinary cytology after radical cystectomy. , 2006, The Journal of urology.

[66]  D. Tilki,et al.  Urethral recurrence after cystectomy: current preventative measures, diagnosis and management , 2016, BJU international.

[67]  J. Wright,et al.  The association between extent of lymphadenectomy and survival among patients with lymph node metastases undergoing radical cystectomy , 2008, Cancer.

[68]  Jian-Min Yuan,et al.  Environmental tobacco smoke and bladder cancer risk in never smokers of Los Angeles County. , 2007, Cancer research.

[69]  M. Qiu,et al.  Meta-analysis of the relationship between slow acetylation of N-acetyl transferase 2 and the risk of bladder cancer. , 2015, Genetics and molecular research : GMR.

[70]  A. Jemal,et al.  Cancer statistics, 2017 , 2017, CA: a cancer journal for clinicians.

[71]  Wassim Kassouf,et al.  Partial cystectomy for muscle invasive urothelial carcinoma of the bladder: a contemporary review of the M. D. Anderson Cancer Center experience. , 2006, The Journal of urology.

[72]  R. Abouassaly,et al.  Increased Use of Cystectomy in Patients 75 and Older: A Contemporary Analysis of Survival and Perioperative Outcomes From the National Cancer Database. , 2017, Urology.

[73]  P. Cinciripini,et al.  Tobacco use and cessation for cancer survivors: An overview for clinicians , 2014, CA: a cancer journal for clinicians.

[74]  D. Penson,et al.  Pathological guidelines for orthotopic urinary diversion in women with bladder cancer: a review of the literature. , 2007, The Journal of urology.

[75]  Chia-Chien Hsu,et al.  The Delphi Technique: Making Sense of Consensus , 2007 .

[76]  F. Burkhard,et al.  Long-term outcome of ileal conduit diversion. , 2003, The Journal of urology.

[77]  Y. Lotan,et al.  Lymphovascular invasion is independently associated with overall survival, cause-specific survival, and local and distant recurrence in patients with negative lymph nodes at radical cystectomy. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[78]  S. Jahnson,et al.  Bladder carcinoma--a 20-year review of radical irradiation therapy. , 1991, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[79]  R. Collins,et al.  Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin. Overview of results of randomized trials in general, orthopedic, and urologic surgery. , 1988, The New England journal of medicine.

[80]  W. Krajewski,et al.  Urinary diversion metabolic complications - underestimated problem. , 2014, Advances in clinical and experimental medicine : official organ Wroclaw Medical University.

[81]  Sam S. Chang,et al.  Alvimopan, a peripherally acting μ-opioid receptor antagonist, is associated with reduced costs after radical cystectomy: economic analysis of a phase 4 randomized, controlled trial. , 2014, The Journal of urology.

[82]  C. Dinney,et al.  Determining the optimal time for radical cystectomy after neoadjuvant chemotherapy , 2018, BJU international.

[83]  M. Borghesi,et al.  The number of nodes removed as well as the template of the dissection is independently correlated to cancer-specific survival after radical cystectomy for muscle-invasive bladder cancer , 2013, International Urology and Nephrology.

[84]  K. Prabhash,et al.  Clinical Outcomes With Dose-Escalated Adaptive Radiation Therapy for Urinary Bladder Cancer: A Prospective Study. , 2016, International journal of radiation oncology, biology, physics.

[85]  J. Shah,et al.  Assessing Symptom Burden in Bladder Cancer: An Overview of Bladder Cancer Specific Health-Related Quality of Life Instruments , 2016, Bladder cancer.

[86]  M. Climent,et al.  Bladder preservation in selected patients with muscle-invasive bladder cancer by complete transurethral resection of the bladder plus systemic chemotherapy: long-term follow-up of a phase 2 nonrandomized comparative trial with radical cystectomy. , 2009, European urology.

[87]  J. Douketis,et al.  Anticoagulants (extended duration) for prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair , 2002 .

[88]  L. Collette,et al.  Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours. , 2006, European journal of cancer.

[89]  A. Kiltie,et al.  Similar treatment outcomes for radical cystectomy and radical radiotherapy in invasive bladder cancer treated at a United Kingdom specialist treatment center. , 2008, International journal of radiation oncology, biology, physics.

[90]  Arnulf Stenzl,et al.  Guidelines on Bladder Cancer Muscle-invasive and Metastatic , 2008 .

[91]  R. Hautmann,et al.  Orthotopic Ileal Neobladder in Females: Impact of the Urethral Resection Line on Functional Results , 2000, International Urogynecology Journal.

[92]  J. Stein,et al.  Pathologic guidelines for orthotopic urinary diversion in women with bladder cancer: a review of the literature. , 2006, Reviews in urology.

[93]  D. Hamstra,et al.  Concurrent gemcitabine and radiotherapy for the treatment of muscle-invasive bladder cancer: A pooled individual data analysis of eight phase I-II trials. , 2016, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[94]  K. Forde,et al.  Combined preoperative mechanical bowel preparation with oral antibiotics significantly reduces surgical site infection, anastomotic leak, and ileus after colorectal surgery. , 2015, Annals of surgery.

[95]  C. Fowler,et al.  Radical radiotherapy and salvage cystectomy for T2/3 cancer of the bladder. , 1988, Progress in clinical and biological research.

[96]  A. Vickers,et al.  Age‐adjusted Charlson comorbidity score is associated with treatment decisions and clinical outcomes for patients undergoing radical cystectomy for bladder cancer , 2008, Cancer.

[97]  D. Penson,et al.  Urinary functional outcomes in female neobladder patients , 2014, World Journal of Urology.

[98]  J. Husband,et al.  Bladder cancer: staging with CT and MR imaging. , 1989, Radiology.

[99]  M. Charlton,et al.  Bladder cancer collaborative stage variables and their data quality, usage, and clinical implications: A review of SEER data, 2004‐2010 , 2014, Cancer.

[100]  V. F. Marshall The relation of the preoperative estimate to the pathologic demonstration of the extent of vesical neoplasms. , 1952, The Journal of urology.

[101]  J. Cheville,et al.  The impact of squamous and glandular differentiation on survival after radical cystectomy for urothelial carcinoma. , 2012, The Journal of urology.

[102]  G. Sonpavde,et al.  A consensus definition of patients with metastatic urothelial carcinoma who are unfit for cisplatin-based chemotherapy. , 2011, The Lancet. Oncology.

[103]  J. Cheville,et al.  The impact of histological reclassification during pathology re-review--evidence of a Will Rogers effect in bladder cancer? , 2013, The Journal of urology.

[104]  S. Holmäng,et al.  Long-term followup of all patients with muscle invasive (stages T2, T3 and T4) bladder carcinoma in a geographical region. , 1997, The Journal of urology.

[105]  Choung-Soo Kim,et al.  FDG PET–CT for Lymph Node Staging of Bladder Cancer: A Prospective Study of Patients with Extended Pelvic Lymphadenectomy , 2015, Annals of Surgical Oncology.

[106]  M. Hawn,et al.  Oral Antibiotic Bowel Preparation Significantly Reduces Surgical Site Infection Rates and Readmission Rates in Elective Colorectal Surgery. , 2015, Annals of surgery.

[107]  H. Barlebo,et al.  Treatment of advanced bladder cancer category T2 T3 and T4a. A randomized multicenter study of preoperative irradiation and cystectomy versus radical irradiation and early salvage cystectomy for residual tumor. DAVECA protocol 8201. Danish Vesical Cancer Group. , 1991, Scandinavian journal of urology and nephrology. Supplementum.

[108]  A. Horgan,et al.  Preoperative Intensive, Community-Based vs. Traditional Stoma Education: A Randomized, Controlled Trial , 2005, Diseases of the colon and rectum.

[109]  Núria Malats,et al.  Smoking and Bladder Cancer in Spain: Effects of Tobacco Type, Timing, Environmental Tobacco Smoke, and Gender , 2006, Cancer Epidemiology Biomarkers & Prevention.

[110]  A. Kader,et al.  Risk factors for infectious readmissions following radical cystectomy: results from a prospective multicenter dataset , 2016, Therapeutic advances in urology.

[111]  W. Kassouf,et al.  Practice patterns and recurrence after partial cystectomy for bladder cancer , 2010, World Journal of Urology.

[112]  S. Boorjian,et al.  Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin is safe, effective, and efficient neoadjuvant treatment for muscle-invasive bladder cancer: results of a multicenter phase II study with molecular correlates of response and toxicity. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[113]  Y. Lotan,et al.  Comprehensive handbook for developing a bladder cancer cystectomy database. , 2013, Urologic oncology.

[114]  M. Dimopoulos,et al.  Prospective, open-label, randomized, phase III study of two dose-dense regimens MVAC versus gemcitabine/cisplatin in patients with inoperable, metastatic or relapsed urothelial cancer: a Hellenic Cooperative Oncology Group study (HE 16/03). , 2013, Annals of oncology : official journal of the European Society for Medical Oncology.

[115]  L. True,et al.  The initial results in muscle-invading bladder cancer of RTOG 95-06: phase I/II trial of transurethral surgery plus radiation therapy with concurrent cisplatin and 5-fluorouracil followed by selective bladder preservation or cystectomy depending on the initial response. , 2000, The oncologist.

[116]  Y. Lotan,et al.  Gender and Bladder Cancer: A Collaborative Review of Etiology, Biology, and Outcomes. , 2016, European urology.

[117]  K. Fearon,et al.  Guidelines for Perioperative Care in Elective Colonic Surgery: Enhanced Recovery after Surgery (eras Clinical Nutrition , 2022 .

[118]  Xiaoping Su,et al.  Intrinsic basal and luminal subtypes of muscle-invasive bladder cancer , 2014, Nature Reviews Urology.

[119]  C. Fowler,et al.  Reappraisal of the role of radical radiotherapy and salvage cystectomy in the treatment of invasive (T2/T3) bladder cancer. , 1988, British journal of urology.

[120]  P. Spiess,et al.  Neoadjuvant Dose Dense MVAC versus Gemcitabine and Cisplatin in Patients with cT3‐4aN0M0 Bladder Cancer Treated with Radical Cystectomy , 2018, The Journal of urology.

[121]  R. Millikan,et al.  Refining patient selection for neoadjuvant chemotherapy before radical cystectomy. , 2014, The Journal of urology.

[122]  R. Hautmann,et al.  ICUD-EAU International Consultation on Bladder Cancer 2012: Urinary diversion. , 2013, European urology.

[123]  F. Montorsi,et al.  Systematic review and cumulative analysis of oncologic and functional outcomes after robot-assisted radical cystectomy. , 2015, European urology.

[124]  S. Pal,et al.  Retrospective analysis of clinical outcomes with neoadjuvant cisplatin-based regimens for muscle-invasive bladder cancer. , 2012, Clinical genitourinary cancer.

[125]  R. Millikan,et al.  Evidence supporting preoperative chemotherapy for small cell carcinoma of the bladder: a retrospective review of the M. D. Anderson cancer experience. , 2004, The Journal of urology.

[126]  T. Ørntoft,et al.  Paired Exome Analysis Reveals Clonal Evolution and Potential Therapeutic Targets in Urothelial Carcinoma. , 2016, Cancer research.

[127]  Jae K. Lee,et al.  A strategy for predicting the chemosensitivity of human cancers and its application to drug discovery , 2007, Proceedings of the National Academy of Sciences.

[128]  A. Zietman,et al.  Selective bladder conservation using transurethral resection, chemotherapy, and radiation: management and consequences of Ta, T1, and Tis recurrence within the retained bladder. , 2001, Urology.

[129]  B. Trock,et al.  Blood Transfusion is Associated with Increased Perioperative Morbidity and Adverse Oncologic Outcomes in Bladder Cancer Patients Receiving Neoadjuvant Chemotherapy and Radical Cystectomy , 2016, Annals of Surgical Oncology.

[130]  B. Lamb,et al.  Complications of Radical Cystectomy and Orthotopic Reconstruction , 2015, Advances in urology.

[131]  F. Marshall,et al.  Local recurrence and survival following nerve sparing radical cystoprostatectomy for bladder cancer: 10-year followup. , 1996, The Journal of urology.

[132]  A. Pycha,et al.  Does extended lymphadenectomy increase the morbidity of radical cystectomy? , 2004, BJU international.

[133]  P. Thall,et al.  Phase II clinical trial of neoadjuvant alternating doublet chemotherapy with ifosfamide/doxorubicin and etoposide/cisplatin in small-cell urothelial cancer. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[134]  P. Javlé,et al.  Orthotopic neobladder versus ileal conduit urinary diversion after cystectomy--a quality-of-life based comparison. , 2009, Annals of the Royal College of Surgeons of England.

[135]  W. Meinhardt,et al.  Local control rate and prognosis after sequential chemoradiation for small cell carcinoma of the bladder , 2013, International journal of urology : official journal of the Japanese Urological Association.

[136]  J. Thüroff,et al.  Lymphadenectomy in patients with transitional cell carcinoma of the urinary bladder; significance for staging and prognosis , 2000, BJU international.

[137]  Andrew H. Beck,et al.  Interobserver Reproducibility in the Diagnosis of Invasive Micropapillary Carcinoma of the Urinary Tract Among Urologic Pathologists , 2010, The American journal of surgical pathology.

[138]  L. Collette,et al.  Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial. , 2015, The Lancet. Oncology.

[139]  D. Amadori,et al.  Gemcitabine plus cisplatin versus gemcitabine plus carboplatin as first-line chemotherapy in advanced transitional cell carcinoma of the urothelium: results of a randomized phase 2 trial. , 2007, European urology.

[140]  A. Hart,et al.  Survival after bladder-preservation with brachytherapy versus radical cystectomy; a single institution experience. , 2005, European urology.

[141]  S Kamen,et al.  The task force. , 1976, Journal of hospital dental practice.

[142]  J. Manola,et al.  Phase III trial of methotrexate, vinblastine, doxorubicin, and cisplatin versus carboplatin and paclitaxel in patients with advanced carcinoma of the urothelium , 2004, Cancer.

[143]  P. Wille-Jørgensen,et al.  Mechanical bowel preparation for elective colorectal surgery. , 2009, The Cochrane database of systematic reviews.

[144]  B. Shayegan,et al.  Management of the urethra in urothelial bladder cancer. , 2013, Canadian Urological Association journal = Journal de l'Association des urologues du Canada.

[145]  F. Carli,et al.  Optimizing a frail elderly patient for radical cystectomy with a prehabilitation program. , 2014, Canadian Urological Association journal = Journal de l'Association des urologues du Canada.

[146]  Mark W. Ball,et al.  Accuracy of urethral frozen section during radical cystectomy for bladder cancer. , 2016, Urologic oncology.

[147]  Scott Harris,et al.  A Meta-analysis of the Effectiveness of the Opioid Receptor Antagonist Alvimopan in Reducing Hospital Length of Stay and Time to GI Recovery in Patients Enrolled in a Standardized Accelerated Recovery Program After Abdominal Surgery , 2012, Diseases of the colon and rectum.

[148]  C. Dinney,et al.  Prostatic urethral biopsy has limited usefulness in counseling patients regarding final urethral margin status during orthotopic neobladder reconstruction. , 2008, The Journal of urology.

[149]  C. Stief,et al.  Malnutrition and clinical outcome in urological patients , 2011, European journal of medical research.

[150]  D. Bergqvist Low molecular weight heparin for the prevention of venous thromboembolism after abdominal surgery , 2004, The British journal of surgery.

[151]  Badrinath R Konety,et al.  Extent of pelvic lymphadenectomy and its impact on outcome in patients diagnosed with bladder cancer: analysis of data from the Surveillance, Epidemiology and End Results Program data base. , 2003, The Journal of urology.

[152]  William Wheeler,et al.  A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci , 2010, Nature Genetics.

[153]  M. Zeegers,et al.  Mechanisms of recurrence of Ta/T1 bladder cancer. , 2010, Annals of the Royal College of Surgeons of England.

[154]  Michael W Kattan,et al.  Prospectively packaged lymph node dissections with radical cystectomy: evaluation of node count variability and node mapping. , 2004, The Journal of urology.

[155]  W. Mcdougal,et al.  Metabolic consequences of urinary diversion through intestinal segments. , 1991, The Urologic clinics of North America.

[156]  M. Gray,et al.  Does preoperative teaching and stoma site marking affect surgical outcomes in patients undergoing ostomy surgery? , 2007, Journal of wound, ostomy, and continence nursing : official publication of The Wound, Ostomy and Continence Nurses Society.

[157]  S. Groshen,et al.  Risk factors for patients with pelvic lymph node metastases following radical cystectomy with en bloc pelvic lymphadenectomy: concept of lymph node density. , 2003, The Journal of urology.

[158]  G. Dalbagni,et al.  Value of urethral wash cytology in the retained male urethra after radical cystoprostatectomy. , 2003, The Journal of urology.

[159]  M. L. Calle,et al.  Genetic susceptibility to distinct bladder cancer subphenotypes. , 2010, European urology.

[160]  A. Zietman,et al.  Organ conservation in invasive bladder cancer by transurethral resection, chemotherapy and radiation: results of a urodynamic and quality of life study on long-term survivors. , 2003, The Journal of urology.

[161]  G. Muto,et al.  Adjuvant chemotherapy with cisplatin and gemcitabine versus chemotherapy at relapse in patients with muscle-invasive bladder cancer submitted to radical cystectomy: an Italian, multicenter, randomized phase III trial. , 2012, Annals of oncology : official journal of the European Society for Medical Oncology.

[162]  Chin-Lee Wu,et al.  Long-Term Outcomes of Organ Preservation in Patients with Small Cell Carcinoma of the Bladder , 2015, Urologia Internationalis.

[163]  H. Grossman,et al.  Surgical factors influence bladder cancer outcomes: a cooperative group report. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[164]  C. Turkelson,et al.  American Academy of Orthopaedic Surgeons clinical practice guideline on: preventing venous thromboembolic disease in patients undergoing elective hip and knee arthroplasty. , 2012, The Journal of bone and joint surgery. American volume.

[165]  V. Laudone,et al.  Comparing Open Radical Cystectomy and Robot-assisted Laparoscopic Radical Cystectomy: A Randomized Clinical Trial. , 2015, European urology.

[166]  W. Lowrance,et al.  Contemporary open radical cystectomy: analysis of perioperative outcomes. , 2008, The Journal of urology.

[167]  Mary R. Kwaan,et al.  Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery. , 2018, The Cochrane database of systematic reviews.

[168]  Paul Russo,et al.  Partial cystectomy: a contemporary review of the Memorial Sloan-Kettering Cancer Center experience and recommendations for patient selection. , 2004, The Journal of urology.

[169]  L. Stassen,et al.  Mechanical bowel preparation for elective colorectal surgery: a multicentre randomised trial , 2007, The Lancet.

[170]  J. Cheville,et al.  Outcomes following radical cystectomy for nested variant of urothelial carcinoma: a matched cohort analysis. , 2013, The Journal of urology.

[171]  B. Bochner,et al.  Pathological response to neoadjuvant chemotherapy for muscle‐invasive micropapillary bladder cancer , 2013, BJU international.

[172]  S. Groshen,et al.  Urethral tumor recurrence following cystectomy and urinary diversion: clinical and pathological characteristics in 768 male patients. , 1999, The Journal of urology.

[173]  A. Roychoudhury,et al.  Relative efficacy of perioperative gemcitabine and cisplatin versus methotrexate, vinblastine, adriamycin, and cisplatin in the management of locally advanced urothelial carcinoma of the bladder. , 2012, Urology.

[174]  B. Somani,et al.  Recent Trends in Postcystectomy Health-related Quality of Life (QoL) Favors Neobladder Diversion: Systematic Review of the Literature. , 2016, Urology.

[175]  A. Zietman,et al.  Bladder Preservation With Twice-a-Day Radiation Plus Fluorouracil/Cisplatin or Once Daily Radiation Plus Gemcitabine for Muscle-Invasive Bladder Cancer: NRG/RTOG 0712-A Randomized Phase II Trial. , 2019, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[176]  L. Carmignani,et al.  Upper urinary tract recurrence following radical cystectomy for bladder cancer: a meta-analysis on 13,185 patients. , 2012, The Journal of urology.

[177]  N. Dubrawsky Cancer statistics , 1989, CA: a cancer journal for clinicians.

[178]  T. Lebret,et al.  Urethral Recurrence of Transitional Cell Carcinoma of the Bladder , 1998, European Urology.

[179]  S. Fosså,et al.  Bladder cancer definitive radiation therapy of muscle‐invasive bladder cancer: A retrospective analysis of 317 patients , 1993, Cancer.

[180]  E. Amini,et al.  Long-term complications of urinary diversion , 2015, Current opinion in urology.

[181]  S. Groshen,et al.  Radical cystectomy for primary neuroendocrine tumors of the bladder: the university of southern california experience. , 2005, The Journal of urology.

[182]  J. Dunst,et al.  Combined-modality treatment and selective organ preservation in invasive bladder cancer: long-term results. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[183]  E. Klein,et al.  Outcome after radical cystectomy with limited or extended pelvic lymph node dissection. , 2008, Journal of Urology.

[184]  S. Hutchings,et al.  Occupation and cancer in Britain , 2010, British Journal of Cancer.

[185]  Jonathan E. Helm,et al.  Sharpening the focus on causes and timing of readmission after radical cystectomy for bladder cancer , 2014, Cancer.

[186]  A. Goenka,et al.  Quality of Life Outcomes for Bladder Cancer Patients Undergoing Bladder Preservation with Radiotherapy , 2015, Current Urology Reports.

[187]  F. Montorsi,et al.  Stage‐specific impact of pelvic lymph node dissection on survival in patients with non‐metastatic bladder cancer treated with radical cystectomy , 2012, BJU international.

[188]  H. Herr Outcome of patients who refuse cystectomy after receiving neoadjuvant chemotherapy for muscle-invasive bladder cancer. , 2008, European urology.

[189]  Weichen Xu,et al.  Postoperative Pain Management after Radical Cystectomy: Comparing Traditional versus Enhanced Recovery Protocol Pathway. , 2015, The Journal of urology.

[190]  H. Scher,et al.  Neoadjuvant chemotherapy and bladder-sparing surgery for invasive bladder cancer: ten-year outcome. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[191]  S. Phillips,et al.  Effect of preoperative nutritional deficiency on mortality after radical cystectomy for bladder cancer. , 2011, The Journal of urology.

[192]  John T. Wei,et al.  Development and validation of the Bladder Cancer Index: a comprehensive, disease specific measure of health related quality of life in patients with localized bladder cancer. , 2010, The Journal of urology.

[193]  A. Zietman,et al.  Phase I-II RTOG study (99-06) of patients with muscle-invasive bladder cancer undergoing transurethral surgery, paclitaxel, cisplatin, and twice-daily radiotherapy followed by selective bladder preservation or radical cystectomy and adjuvant chemotherapy. , 2009, Urology.

[194]  A. Zietman,et al.  Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial. , 2013, The Lancet. Oncology.

[195]  R. Zlotecki,et al.  Treatment of Small Cell Carcinoma of the Bladder With Chemotherapy and Radiation after Transurethral Resection of a Bladder Tumor , 2016, American journal of clinical oncology.

[196]  Cary Siegel,et al.  Prospective study of [18F]fluorodeoxyglucose positron emission tomography/computed tomography for staging of muscle-invasive bladder carcinoma. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[197]  E. Elkin,et al.  Risk of fracture after radical cystectomy and urinary diversion for bladder cancer. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[198]  M. Tsivian,et al.  The characteristics of bladder cancer after radiotherapy for prostate cancer. , 2013, Urologic oncology.

[199]  S. Shariat,et al.  Effect of smoking on outcomes of urothelial carcinoma: a systematic review of the literature. , 2014, European urology.

[200]  John D Seigne,et al.  Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer: AUA/SUO Guideline. , 2016, The Journal of urology.

[201]  Paolo Vineis,et al.  A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer , 2010, Nature Genetics.

[202]  A. Gerbaulet,et al.  Interstitial iridium-192 for bladder cancer (a multicentric survey: 205 patients). , 1992, International Journal of Radiation Oncology, Biology, Physics.

[203]  Steven L. Chang,et al.  Adjuvant chemotherapy for invasive bladder cancer: a 2013 updated systematic review and meta-analysis of randomized trials. , 2014, European urology.

[204]  S. Kropf,et al.  Extended radical lymphadenectomy in patients with urothelial bladder cancer: results of a prospective multicenter study. , 2004, The Journal of urology.

[205]  M. Metcalfe,et al.  Role of preoperative carbohydrate loading: a systematic review , 2014, Annals of the Royal College of Surgeons of England.

[206]  J. Cheville,et al.  The impact of perioperative blood transfusion on cancer recurrence and survival following radical cystectomy. , 2013, European urology.

[207]  F. Freiha,et al.  A randomized trial of radical cystectomy versus radical cystectomy plus cisplatin, vinblastine and methotrexate chemotherapy for muscle invasive bladder cancer. , 1996, The Journal of urology.

[208]  F. Burkhard,et al.  Super extended versus extended pelvic lymph node dissection in patients undergoing radical cystectomy for bladder cancer: a comparative study. , 2011, The Journal of urology.

[209]  David C. Smith,et al.  Prospective quality-of-life assessment in patients receiving concurrent gemcitabine and radiotherapy as a bladder preservation strategy. , 2004, Urology.

[210]  J. Stein,et al.  Indications and technique of the orthotopic neobladder in women. , 2002, The Urologic clinics of North America.

[211]  H. V. Van Poppel,et al.  Metabolic Changes after Urinary Diversion , 2011, Advances in urology.

[212]  C. la Vecchia,et al.  The Role of Tobacco Smoke in Bladder and Kidney Carcinogenesis: A Comparison of Exposures and Meta-analysis of Incidence and Mortality Risks. , 2016, European urology.

[213]  S. Gabriel,et al.  Somatic ERCC2 mutations correlate with cisplatin sensitivity in muscle-invasive urothelial carcinoma. , 2014, Cancer discovery.

[214]  L. Holmberg,et al.  Neoadjuvant Cisplatin-Methotrexate Chemotherapy for Invasive Bladder Cancer - Nordic Cystectomy Trial 2 , 2002, Scandinavian journal of urology and nephrology.

[215]  S. Weber,et al.  The impact of mechanical bowel preparation on postoperative complications for patients undergoing cystectomy and urinary diversion. , 2012, The Journal of urology.

[216]  Michael W Kattan,et al.  Postoperative nomogram predicting risk of recurrence after radical cystectomy for bladder cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[217]  T. Kessler,et al.  Twenty years experience with an ileal orthotopic low pressure bladder substitute--lessons to be learned. , 2006, The Journal of urology.

[218]  S. Shariat,et al.  Is continent cutaneous urinary diversion a suitable alternative to orthotopic bladder substitute and ileal conduit after cystectomy? , 2015, BJU international.

[219]  W. Mackillop,et al.  Lymph node counts are valid indicators of the quality of surgical care in bladder cancer: a population-based study. , 2015, Urologic oncology.

[220]  D. Parekh,et al.  Perioperative outcomes and oncologic efficacy from a pilot prospective randomized clinical trial of open versus robotic assisted radical cystectomy. , 2013, The Journal of urology.

[221]  John D. Roberts,et al.  RTOG 97-06: initial report of a phase I-II trial of selective bladder conservation using TURBT, twice-daily accelerated irradiation sensitized with cisplatin, and adjuvant MCV combination chemotherapy. , 2003, International journal of radiation oncology, biology, physics.

[222]  U. Studer,et al.  Orthotopic ileal bladder substitution in women: factors influencing urinary incontinence and hypercontinence. , 2015, European urology.

[223]  Nicholas J Vogelzang,et al.  Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. , 2003, The New England journal of medicine.

[224]  T. Terada Small cell carcinoma of the urinary bladder. , 2012, International journal of clinical and experimental pathology.

[225]  Ronald C. Chen,et al.  Patterns of Bladder Preservation Therapy Utilization for Muscle-Invasive Bladder Cancer , 2016, Bladder cancer.

[226]  S. Fosså,et al.  Neoadjuvant chemotherapy in bladder cancer: a randomized study. Nordic Cystectomy Trial I. , 1993, Scandinavian journal of urology and nephrology.

[227]  R. Leveillee,et al.  AUA Best Practice Statement for the prevention of deep vein thrombosis in patients undergoing urologic surgery. , 2009, The Journal of urology.

[228]  D. Silverman,et al.  Hair dye use and risk of bladder cancer in the New England bladder cancer study , 2011, International journal of cancer.

[229]  S. Raab Comparison of ImmunoCyt, UroVysion, and Urine Cytology in Detection of Recurrent Urothelial Carcinoma: A “Split-Sample” Study , 2010 .

[230]  Cui Yu,et al.  Gemcitabine/cisplatin versus methotrexate/vinblastine/doxorubicin/cisplatin for muscle-invasive bladder cancer: A systematic review and meta-analysis , 2018, Journal of cancer research and therapeutics.

[231]  T. Kakizoe,et al.  Transitional cell carcinoma of the urethra in men following cystectomy for bladder cancer: multivariate analysis for risk factors. , 1991, The Journal of urology.

[232]  E. Wallen,et al.  Prospective randomized controlled trial of robotic versus open radical cystectomy for bladder cancer: perioperative and pathologic results. , 2010, European urology.

[233]  A. Harraz,et al.  Renal function evaluation in patients undergoing orthotopic bladder substitution: a systematic review of literature , 2014, BJU international.

[234]  J. Cheville,et al.  Clinical predictors and survival outcome of patients receiving suboptimal neoadjuvant chemotherapy and radical cystectomy for muscle-invasive bladder cancer: a single-center experience , 2019, World Journal of Urology.

[235]  J. Efstathiou,et al.  Complications and long-term results of salvage cystectomy after failed bladder sparing therapy for muscle invasive bladder cancer. , 2012, The Journal of urology.

[236]  J. Cheville,et al.  Delaying Radical Cystectomy After Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer is Associated with Adverse Survival Outcomes. , 2019, European urology oncology.

[237]  M. Ghoneim,et al.  Surgical complications following radical cystectomy and orthotopic neobladders in women. , 2008, The Journal of urology.

[238]  P. Warde,et al.  Bladder cancer: long-term follow-up results of patients treated with radical radiation. , 1991, Clinical oncology (Royal College of Radiologists (Great Britain)).

[239]  D. Parekh,et al.  Health‐related quality of life from a prospective randomised clinical trial of robot‐assisted laparoscopic vs open radical cystectomy , 2014, BJU international.

[240]  T. Clozel,et al.  Predictors of Survival in Patients With Soft Tissue Surgical Margin Involvement at Radical Cystectomy , 2013, Annals of Surgical Oncology.

[241]  K. Nakagawa,et al.  Role of pelvic lymph node dissection in lymph node-negative patients with invasive bladder cancer. , 2010, Japanese journal of clinical oncology.

[242]  A. El-Hefnawy,et al.  Female sexual dysfunction post radical cystectomy and urinary diversion , 2016, Climacteric : the journal of the International Menopause Society.

[243]  Mårten Fernö,et al.  A Molecular Taxonomy for Urothelial Carcinoma , 2012, Clinical Cancer Research.

[244]  G. Muto,et al.  Complications following radical cystectomy for bladder cancer in the elderly. , 2009, European urology.

[245]  W. H. Kern,et al.  The role of adjuvant chemotherapy following cystectomy for invasive bladder cancer: a prospective comparative trial. , 1991, The Journal of urology.

[246]  I. Shabo,et al.  PET/CT versus conventional CT for detection of lymph node metastases in patients with locally advanced bladder cancer , 2015, BMC Urology.

[247]  Sanjay G. Patel,et al.  Locoregional small cell carcinoma of the bladder: clinical characteristics and treatment patterns. , 2014, The Journal of urology.

[248]  W. Mackillop,et al.  Concurrent chemoradiotherapy for bladder cancer: Practice patterns and outcomes in the general population. , 2018, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[249]  H. Bartelink,et al.  Organ preservation in invasive bladder cancer: brachytherapy, an alternative to cystectomy and combined modality treatment? , 2005, International journal of radiation oncology, biology, physics.

[250]  C. Vale Adjuvant chemotherapy for invasive bladder cancer (individual patient data). , 2006, The Cochrane database of systematic reviews.

[251]  H. Herr,et al.  Transurethral resection of muscle-invasive bladder cancer: 10-year outcome. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[252]  R. Hautmann,et al.  Lessons learned from 1,000 neobladders: the 90-day complication rate. , 2010, The Journal of urology.

[253]  J. Cheville,et al.  Risk factors and outcomes of urethral recurrence following radical cystectomy. , 2011, European urology.

[254]  M. Ducreux,et al.  Adjuvant chemotherapy in locally advanced bladder cancer , 2015 .