Attention: Restrictions on use of AUA, AUAER, and UCF content in third party applications, including artificial intelligence technologies, such as large language models and generative AI.
You are prohibited from using or uploading content you accessed through this website into external applications, bots, software, or websites, including those using artificial intelligence technologies and infrastructure, including deep learning, machine learning and large language models and generative AI.

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

Using AUA Guidelines

This AUA guideline is provided free of use to the general public for academic and research purposes. However, any person or company accessing AUA guidelines for promotional or commercial use must obtain a licensed copy. To obtain the licensable copy of this guideline, please contact Keith Price at kprice@auanet.org.

To cite this guideline:

Holzbeierlein J, Bixler BR, Buckley DI, et al. Treatment of non-metastatic muscle-invasive bladder cancer: AUA/ASCO/SUO guideline (2017; amended 2020, 2024). J Urol. Published online April 25, 2024. doi:10.1097/JU.0000000000003981 https://www.auajournals.org/doi/10.1097/JU.0000000000003981

Published 2017; Amended 2020, 2024

Unabridged version of this Guideline [pdf]
Algorithm associated with this Guideline [pdf]
Cancer Care Ontario Endorsement 
Español translated 2017 guideline courtesy of Confederacion Americana de Urologia (CAU) [pdf]

Panel Members

Sam S. Chang, MD, MBA; Bernard H. Bochner, MD; Roger Chou, MD; Robert Dreicer, MD, MS, MACP; Ashish M. Kamat, MD, MBBS; Seth P. Lerner, MD; Yair Lotan, MD; Joshua J. Meeks, MD, PhD; Jeff M. Michalski, MD, MBA; Todd M. Morgan, MD; Diane Z. Quale; Jonathan E. Rosenberg, MD; Anthony L. Zietman, MD; Jeffrey M. Holzbeierlein, MD

2020 Amendment Panel

James M. McKiernan, MD; Christopher B. Anderson, MD; Sam S. Chang, MD, MBA; John L. Gore, MD; Jeffrey M. Holzbeierlein, MD

2024 Amendment Panel

Jeffrey M. Holzbeierlein, MD; Sam S. Chang, MD, MBA; Andrew C. James, MD; James M. McKiernan, MD; Anne Schuckman, MD

Staff and Consultants

David I. Buckley, MD, MPH; Rebecca S. Holmes, MD, MS; Brooke R. Bixler, MPH; Erin Kirkby, MS

SUMMARY

Purpose

Although representing approximately 25% of patients diagnosed with bladder cancer, muscle-invasive bladder cancer (MIBC) carries a significant risk of death that has not significantly changed in decades. Increasingly, clinicians and patients recognize the importance of multidisciplinary collaborative efforts that take into account survival and quality of life (QOL) concerns. For the first time for any type of malignancy, the American Urological Association (AUA), the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO), and the Society of Urologic Oncology (SUO) collaborated on an evidence-based guideline. This guideline provides a risk-stratified clinical framework for the management of muscle-invasive urothelial bladder cancer and is designed to be used in conjunction with the associated treatment algorithm.

Methodology

The systematic review utilized to inform this guideline was conducted by a methodology team at the Pacific Northwest Evidence-based Practice Center. The original review was funded by the Agency for Healthcare Research and Quality (AHRQ), and a subsequent supplemental report was funded by the AUA to address additional key questions and more recently published literature. A research librarian experienced in conducting literature searches for comparative effectiveness reviews searched in Ovid MEDLINE® (January 1990 to October 2014), the Cochrane Central Register of Controlled Trials (through September 2014), the Cochrane Database of Systematic Reviews (through September 2014), Health Technology Assessments (through Third Quarter 2014), the National Health Sciences Economic Evaluation Database (through Third Quarter 2014), and the Database of Abstracts of Reviews of Effects (through Third Quarter 2014) to capture published and gray literature. The methodology team searched for unpublished studies in clinical trial registries (ClinicalTrials.gov, Current Controlled Trials, ClinicalStudyResults.org and the World Health Organization International Clinical Trials Registry Platform) and regulatory documents (Drugs@FDA.gov and FDA Medical Devices Registration and Listing). A supplemental search of Ovid MEDLINE and Cochrane Central Register of Controlled Trials was conducted to capture additional published literature through February 2, 2016. The guideline underwent review in 2020. The updated search (July 1, 2016 to May 18, 2020) identified 2,005 abstracts, of which 38 met inclusion criteria. An additional review was performed in 2023. The updated search (May 2020 to November 2023) identified 3,739 abstracts, of which 46 met inclusion criteria. When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A (high), B (moderate) or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. 

GUIDELINE STATEMENTS

Initial Patient Evaluation and Counseling

  1. Prior to treatment consideration, a full history and physical exam should be performed, including an exam under anesthesia, at the time of transurethral resection of bladder tumor (TURBT) for a suspected invasive cancer. (Clinical Principle)
  2. Prior to muscle-invasive bladder cancer management, clinicians should perform a complete staging evaluation, including imaging of the chest and cross sectional imaging of the abdomen and pelvis with intravenous contrast if not contraindicated. Laboratory evaluation should include a comprehensive metabolic panel (complete blood count, liver function tests, alkaline phosphatase, and renal function). (Clinical Principle)
  3. An experienced genitourinary pathologist should review the pathology of a patient when variant histology is suspected or if muscle invasion is equivocal (e.g., micropapillary, nested, plasmacytoid, neuroendocrine, sarcomatoid, extensive squamous or glandular differentiation). (Clinical Principle)
  4. For patients with newly diagnosed muscle-invasive bladder cancer, curative treatment options should be discussed before determining a plan of therapy that is based on both patient comorbidity and tumor characteristics. Patient evaluation should be completed using a multidisciplinary approach. (Clinical Principle)
  5. Prior to treatment, clinicians should counsel patients regarding complications and the implications of treatment on QOL (e.g., impact on continence, sexual function, fertility, bowel dysfunction, metabolic problems). (Clinical Principle)

Treatment

Neoadjuvant/Adjuvant Chemotherapy

  1. Utilizing a multidisciplinary approach, clinicians should offer cisplatin-based neoadjuvant chemotherapy (NAC) to eligible radical cystectomy patients prior to cystectomy. (Strong Recommendation; Evidence Level: Grade B)
  2. Clinicians should not prescribe carboplatin-based NAC for clinically resectable stage cT2-T4aN0 bladder cancer. Patients ineligible for cisplatin-based NAC should proceed to definitive locoregional therapy or clinical trial. (Expert Opinion)
  3. Clinicians should perform radical cystectomy as soon as possible following a patient’s completion of and recovery from NAC (ideally within 12 weeks unless medically inadvisable). (Expert Opinion)
  4. Patients who have not received cisplatin-based NAC and have pT3-4and/or N+ disease at cystectomy should be offered adjuvant cisplatin-based chemotherapy or adjuvant immunotherapy. Patients who have received cisplatin-based chemotherapy and have pT2-4and/or N+ at cystectomy should be offered adjuvant immunotherapy. (Moderate Recommendation; Evidence Level: Grade C)

Radical Cystectomy

  1. Clinicians should offer radical cystectomy with bilateral pelvic lymphadenectomy for surgically eligible patients with resectable non-metastatic (M0) muscle-invasive bladder cancer. (Strong Recommendation; Evidence Level: Grade B)
  2. When performing a standard radical cystectomy with curative intent, clinicians should remove the bladder, prostate, and seminal vesicles in males; clinicians should remove the bladder in females and should consider removal of adjacent reproductive organs based on individual disease characteristics and need to obtain negative margins. Organ sparing procedures in females should be considered based on disease location and characteristics on an individual basis. (Clinical Principle)
  3. Clinicians should discuss and consider sexual function preserving procedures for patients with organ-confined disease and absence of bladder neck, urethra, and prostate (male) involvement. (Moderate Recommendation; Evidence Level: Grade C)

Urinary Diversion

  1. In patients undergoing radical cystectomy, ileal conduit, continent cutaneous, and orthotopic neobladder urinary diversions should all be discussed. (Clinical Principle)
  2. In patients receiving an orthotopic urinary diversion, clinicians must verify a negative urethral margin. (Clinical Principle)

Perioperative Surgical Management

  1. Clinicians should attempt to optimize patient performance status (PS) in the perioperative setting. (Expert Opinion)
  2. Perioperative pharmacologic thromboembolic prophylaxis should be given to patients undergoing radical cystectomy. (Strong Recommendation; Evidence Level: Grade B)
  3. In patients undergoing radical cystectomy µ -opioid antagonist therapy should be used to accelerate gastrointestinal recovery, unless contraindicated. (Strong Recommendation; Evidence Level: Grade B)
  4. Patients should receive detailed teaching regarding care of urinary diversion prior to discharge from the hospital. (Clinical Principle)

Pelvic Lymphadenectomy

  1. Clinicians must perform a bilateral pelvic lymphadenectomy at the time of any surgery with curative intent. (Strong Recommendation; Evidence Level: Grade B)
  2. When performing bilateral pelvic lymphadenectomy, clinicians should remove, at a minimum, the external and internal iliac and obturator lymph nodes (standard lymphadenectomy). (Clinical Principle)

Bladder Preserving Approaches

Patient Selection

  1. For patients with newly diagnosed non-metastatic muscle-invasive bladder cancer who desire to retain their bladder, and for those with significant comorbidities for whom radical cystectomy is not a treatment option, clinicians should offer bladder preserving therapy when clinically appropriate. (Clinical Principle)
  2. In patients under consideration for bladder preserving therapy, maximal debulking TURBT and assessment of multifocal disease/carcinoma in situ (CIS) should be performed. (Strong Recommendation; Evidence Level: Grade C)

Maximal TURBT and Partial Cystectomy

  1. Patients with muscle-invasive bladder cancer who are medically fit and consent to radical cystectomy should not undergo partial cystectomy or maximal TURBT as primary curative therapy. (Moderate Recommendation; Evidence Level: Grade C)

Primary Radiation Therapy

  1. For patients with muscle-invasive bladder cancer, clinicians should not offer radiation therapy alone as a curative treatment. (Strong Recommendation; Evidence Level: Grade C)

Multi-Modal Bladder Preserving Therapy

  1. For patients with muscle-invasive bladder cancer who have elected tri-modality therapy with organ preservation, clinicians should offer maximal TURBT followed by chemotherapy combined with external beam radiation therapy (EBRT). Planned cystoscopic surveillance per high-risk NMIBC schedule should be performed. (Strong Recommendation; Evidence Level: Grade B)
  2. Radiation sensitizing chemotherapy should be included when using multimodal therapy with curative intent. (Strong Recommendation; Evidence Level: Grade B)
  3. Following completion of bladder preserving therapy, clinicians should perform regular surveillance with computed tomography (CT) scans, cystoscopy, and urine cytology. (Strong Recommendation; Evidence Level: Grade C)

Bladder Preserving Treatment Failure

  1. In patients who are medically fit and have residual or recurrent muscle-invasive disease following bladder preserving therapy, clinicians should offer radical cystectomy with bilateral pelvic lymphadenectomy. (Strong Recommendation; Evidence Level: Grade C)
  2. In patients who have a non-muscle invasive recurrence after bladder preserving therapy, clinicians may offer either local measures, such as TURBT with intravesical therapy, or radical cystectomy with bilateral pelvic lymphadenectomy. (Moderate Recommendation; Evidence Level: Grade C)

Patient Surveillance and Follow Up

Imaging

  1. Clinicians should obtain chest imaging and cross-sectional imaging of the abdomen and pelvis with CT or magnetic resonance imaging (MRI) at 6-12 month intervals for 2-3 years and then may continue annually. (Expert Opinion)  

Laboratory Values and Urine Markers

  1. Following therapy for muscle-invasive bladder cancer, patients should undergo laboratory assessment at three to six month intervals for two to three years and then annually thereafter. (Expert Opinion)
  2. Following radical cystectomy in patients with a retained urethra, clinicians should monitor the urethral remnant for recurrence. (Expert Opinion)

Patient Survivorship

  1. Clinicians should discuss with patients how they are coping with their bladder cancer diagnosis and treatment and should recommend that patients consider participating in cancer support groups or consider receiving individual counseling. (Expert Opinion)
  2. Clinicians should encourage bladder cancer patients to adopt healthy lifestyle habits, including smoking cessation, exercise, and a healthy diet, to improve long-term health and QOL. (Expert Opinion)

Variant Histology

  1. In patients diagnosed with variant histology, clinicians should consider unique clinical characteristics that may require divergence from standard evaluation and management for urothelial carcinoma. (Expert Opinion)

INTRODUCTION

Methodology

Systematic Review

The systematic review utilized to inform this guideline was conducted by a methodology team at the Pacific Northwest Evidence-based Practice Center. The original review was funded by AHRQ,1 and a subsequent supplemental report was funded by the AUA to address additional key questions and more recently published literature. A research librarian experienced in conducting literature searches for comparative effectiveness reviews searched in Ovid MEDLINE® (January 1990 to October 2014), the Cochrane Central Register of Controlled Trials (through September 2014), the Cochrane Database of Systematic Reviews (through September 2014), Health Technology Assessments (through Third Quarter 2014), the National Health Sciences Economic Evaluation Database (through Third Quarter 2014), and the Database of Abstracts of Reviews of Effects (through Third Quarter 2014) to capture published and gray literature. The methodology team searched for unpublished studies in clinical trial registries (ClinicalTrials.gov, Current Controlled Trials, ClinicalStudyResults.org and the World Health Organization International Clinical Trials Registry Platform) and regulatory documents (Drugs@FDA.gov and FDA Medical Devices Registration and Listing). Reference lists of relevant studies and previous systematic reviews were hand-searched for additional studies. Scientific information packets were solicited from drug and device manufacturers and via a notice published in the Federal Register. Initial Database searches resulted in 3,921 potentially relevant articles. After dual review of abstracts and titles, 295 articles were selected for full-text dual review, and 39 studies (in 41 publications) were determined to meet inclusion criteria and were included in this review. A supplemental search of Ovid MEDLINE and Cochrane Central Register of Controlled Trials was conducted to capture additional published literature through February 2, 2016.

In 2020, the MIBC guideline was updated through the AUA amendment process in which newly published literature is reviewed and integrated into previously published guidelines in an effort to maintain currency. The amendment allowed for the incorporation of additional literature released since the initial publication of this guideline in 2017. For this literature review the methodology team searched Ovid MEDLINE(R) ALL from July 1, 2016 to May 18, 2020 (overlapping with search dates for the 2016 review ending October 6, 2016), and eliminated duplicate abstracts reviewed for earlier reports. The literature search identified 2,005 abstracts, of which 38 met inclusion criteria. Two of these citations were from secondary publications of another study included in this update or a previous report. Seven abstracts reported RCTs, 29 observational studies, and 2 systematic reviews.

An additional update was performed in 2023. The updated search gathered literature from May 2020 to November 2023 using Ovid MEDLINE(R) ALL and eliminated duplicate abstracts reviewed for earlier reports. This review identified 3,739 abstracts, of which 46 met inclusion criteria. Eleven of these citations were from secondary publications of another study included in this update or a previous report. Nine studies were randomized controlled trials (RCTs), two non-randomized trials, 19 observational studies, and five systematic reviews.

Data Extraction and Data Management

The methodology team extracted the following information into evidence tables: study design; setting; inclusion and exclusion criteria; dose and duration of treatment for experimental and control groups; duration of follow up; number of subjects screened, eligible, and enrolled; population ES-5 characteristics (including age, race/ethnicity, sex, stage of disease, and functional status); results; adverse events; withdrawals due to adverse events; and sources of funding. Methodologists verified or calculated relative risks and associated 95% confidence intervals (CIs) based on the information provided (sample sizes and incidence of outcomes in each intervention group). Methodologists noted discrepancies between calculated and reported results when present. Data extraction for each study was completed by one investigator and independently reviewed for accuracy and completeness by a second investigator.

Assessment of the Risk of Bias of Individual Studies

The methodology team assessed the risk of bias for RCTs and observational studies using criteria adapted from those developed by the U.S. Preventive Services Task Force.2, 3 These criteria were applied in conjunction with the approach recommended in the AHRQ Methods Guide3 for medical interventions. Two investigators independently assessed the risk of bias of each study. Discrepancies were resolved through discussion and consensus. Each study was rated as low, medium, or high risk of bias. Methodologists rated the quality of each RCT based on the methods used for randomization, allocation concealment, and blinding; the similarity of compared groups at baseline; whether attrition was adequately reported and acceptable; similarity in use of co-interventions; compliance with allocated treatments; the use of intent-to-treat analysis; and avoidance of selective outcomes reporting.2 Methodologists rated the quality of each cohort study based on whether it enrolled a consecutive or random sample of patients meeting inclusion criteria; whether it evaluated comparable groups; whether rates of loss to follow up were reported and acceptable; whether it used accurate methods for ascertaining exposures, potential confounders, and outcomes; and whether it performed adjustment for important potential confounders (defined as a minimum of age, sex, tumor stage, and tumor grade).2 Studies rated low risk of bias were considered to have no more than very minor methodological shortcomings with their results likely to be valid. Studies rated medium risk of bias have some methodological shortcomings, but no flaw or combination of flaws judged likely to cause major bias. In some cases, the article did not report important information, making it difficult to assess its methods or potential limitations. The category of medium risk of bias is broad, and studies with this rating vary in their strengths and weaknesses; the results of some studies assessed to have medium risk of bias are likely to be valid, while others may be only possibly valid. Studies rated high risk of bias have significant flaws that may invalidate the results. They have a serious or fatal flaw or combination of flaws in design, analysis, or reporting; large amounts of missing information (including publication of only preliminary results in a subgroup of patients randomized); or serious discrepancies in reporting. Methodologists did not exclude studies rated as having high risk of bias a priori, but they were considered the least reliable when synthesizing the evidence, particularly when discrepancies between studies were present.

Determination of Evidence Strength

The Grading of Recommendations Assessment, Development, and Evaluation (GRADE)4 system was used to determine the aggregate evidence quality for each outcome, or group of related outcomes, informing Key Questions.  GRADE defines a body of evidence in relation to how confident guideline developers can be that the estimate of effects as reported by that body of evidence is correct.  Evidence is categorized as high, moderate, low and very low, and assessment is based on the aggregate risk of bias for the evidence base, plus limitations introduced as a consequence of inconsistency, indirectness, imprecision and publication bias across the studies.  Upgrading of evidence is possible if the body of evidence indicates a large effect or if confounding factors would suggest either spurious effects or would reduce the demonstrated effect. 

The AUA employs a 3-tiered strength of evidence system to underpin evidence-based guideline statements.  Table 1 summarizes the GRADE categories, definitions and how these categories translate to the AUA strength of evidence categories.  High certainty by GRADE translates to AUA A category strength of evidence, moderate to B, and both low and very low to C. 

TABLE 1: Strength of Evidence Definition

AUA Strength of Evidence Category

GRADE Certainty Rating

Definition

A

High

• Very confident that the true effect lies close to that of the estimate of the effect

B

Moderate

•Moderately confident in the effect estimate

• The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different

C

Low
 

 

 

Very Low

• Confidence in the effect estimate is limited

• The true effect may be substantially different from the estimate of the effect

 

• Very little confidence in the effect estimate

• The true effect is likely to be substantially different from the estimate of effect

 

AUA Nomenclature: Linking Statement Type to Evidence Strength

The AUA nomenclature system explicitly links statement type to body of evidence strength, level of certainty, magnitude of benefit or risk/burdens, and the Panel’s judgment regarding the balance between benefits and risks/burdens (Table 2). Strong Recommendations are directive statements that an action should (benefits outweigh risks/burdens) or should not (risks/burdens outweigh benefits) be undertaken because net benefit or net harm is substantial. Moderate Recommendations are directive statements that an action should (benefits outweigh risks/burdens) or should not (risks/burdens outweigh benefits) be undertaken because net benefit or net harm is moderate. Conditional Recommendations are non-directive statements used when the evidence indicates that there is no apparent net benefit or harm or when the balance between benefits and risks/burden is unclear. All three statement types may be supported by any body of evidence strength grade. Body of evidence strength Grade A in support of a Strong or Moderate Recommendation indicates that the statement can be applied to most patients in most circumstances and that future research is unlikely to change confidence. Body of evidence strength Grade B in support of a Strong or Moderate Recommendation indicates that the statement can be applied to most patients in most circumstances but that better evidence could change confidence. Body of evidence strength Grade C in support of a Strong or Moderate Recommendation indicates that the statement can be applied to most patients in most circumstances but that better evidence is likely to change confidence. Body of evidence strength Grade C is only rarely used in support of a Strong Recommendation. Conditional Recommendations also can be supported by any evidence strength. When body of evidence strength is Grade A, the statement indicates that benefits and risks/burdens appear balanced, the best action depends on patient circumstances, and future research is unlikely to change confidence. When body of evidence strength Grade B is used, benefits and risks/burdens appear balanced, the best action also depends on individual patient circumstances and better evidence could change confidence. When body of evidence strength Grade C is used, there is uncertainty regarding the balance between benefits and risks/burdens, alternative strategies may be equally reasonable, and better evidence is likely to change confidence.

Where gaps in the evidence existed, the Panel provides guidance in the form of Clinical Principles or Expert Opinion with consensus achieved using a modified Delphi technique if differences of opinion emerged.5 A Clinical Principle is a statement about a component of clinical care that is widely agreed upon by urologists or other clinicians for which there may or may not be evidence in the medical literature. Expert Opinion refers to a statement, achieved by consensus of the Panel, that is based on members' clinical training, experience, knowledge, and judgment for which there may or may not be evidence in the medical literature.

TABLE 2: AUA Nomenclature Linking Statement Type to Level of Certainty, Magnitude of Benefit or Risk/Burden, and Body of Evidence Strength

 

Evidence Strength A

(High Certainty)

Evidence Strength B

(Moderate Certainty)

Evidence Strength C

(Low Certainty)

Strong Recommendation

 

(Net benefit or harm substantial)

Benefits > Risks/Burdens (or vice versa)

Net benefit (or net harm) is substantial

Applies to most patients in most circumstances and future research is unlikely to change confidence

Benefits > Risks/Burdens (or vice versa)

Net benefit (or net harm) is substantial

Applies to most patients in most circumstances but better evidence could change confidence

 

Benefits > Risks/Burdens (or vice versa)

Net benefit (or net harm) appears substantial

Applies to most patients in most circumstances but better evidence is likely to change confidence

(rarely used to support a Strong Recommendation)

Moderate Recommendation

 

(Net benefit or harm moderate)

Benefits > Risks/Burdens (or vice versa)

Net benefit (or net harm) is moderate

Applies to most patients in most circumstances and future research is unlikely to change confidence

Benefits > Risks/Burdens (or vice versa)

Net benefit (or net harm) is moderate

Applies to most patients in most circumstances but better evidence could change confidence

Benefits > Risks/Burdens (or vice versa)

Net benefit (or net harm) appears moderate

Applies to most patients in most circumstances but better evidence is likely to change confidence

Conditional Recommendation

 

(No apparent net benefit or harm)

Benefits = Risks/Burdens

Best action depends on individual patient circumstances

Future research unlikely to change confidence

Benefits = Risks/Burdens

Best action appears to depend on individual patient circumstances

Better evidence could change confidence

Balance between Benefits & Risks/Burdens unclear

Alternative strategies may be equally reasonable

Better evidence likely to change confidence

Clinical Principle

A statement about a component of clinical care that is widely agreed upon by urologists or other clinicians for which there may or may not be evidence in the medical literature

Expert Opinion

A statement, achieved by consensus of the Panel, that is based on members' clinical training, experience, knowledge, and judgment for which may or may not be evidence in the medical literature

Process

The Muscle-Invasive Bladder Cancer Panel was created in 2014 by the American Urological Association Education and Research, Inc. (AUA). The Practice Guidelines Committee (PGC) of the AUA selected the Panel Chair who in turn appointed the Vice Chair. In a collaborative process, additional Panel members, including additional members of ASTRO, ASCO, and SUO, with specific expertise in this area were then nominated and approved by the PGC. The AUA conducted a thorough peer review process. The draft guideline document was distributed to 128 peer reviewers, 67 of which submitted comments. The Panel reviewed and discussed all submitted comments and revised the draft as needed. Once finalized, the guideline was submitted for approval to the PGC and Science and Quality Council. Then it was submitted to the AUA, ASTRO, ASCO, and SUO Board of Directors for final approval. Panel members received no remuneration for their work. This represents the first joint guidelines by these organizations.

The 2020 and 2024 amendments also underwent peer review. The draft 2020 amendment was distributed to 69 peer reviewers, 18 of whom submitted 38 comments. The 2024 amendment was distributed to 61 peer reviewers, 20 of whom submitted 67 comments. Following each amendment, Panels reviewed and discussed all submitted comments and revised the draft as needed. Once finalized, the amendments were submitted for approval.

Background

Epidemiology

There are 83,190 new cases of bladder cancer and 16,840 bladder cancer deaths estimated for 2024 in the U.S.6 Approximately 25% of newly diagnosed patients have muscle-invasive disease,7, 8 a rate that has not changed over the last 10 years based on data from the Surveillance, Epidemiology, and End Results (SEER) registry.9 In addition, up to 50% or more patients with high-risk non-muscle invasive bladder cancer (NMIBC) can progress to invasive disease. The male to female ratio is 3:1, and disease incidence increases with age. While rates of bladder cancer are higher in Caucasians than other ethnicities, disease specific survival is worse overall for African-Americans.8, 10

Etiology

All of the factors that contribute to the development of bladder cancer are not completely understood, but exposure to carcinogens (e.g., tobacco smoke) is the primary cause with some impact from genetic susceptibility. Smoking tobacco is the most important and common risk factor and is estimated to contribute to the development of 50% of bladder tumors, with current smokers at higher risk than former smokers.11, 12 Former smoking increases the risk of bladder cancer by a factor of 2.2 (95% CI: 2.0 to 2.4), and current smoking by a factor of 4.1 (95% CI: 3.7 to 4.5) compared to never having smoked.11 Second hand smoke can also increase the risk for the development of bladder cancer.13 Following smoking, another risk factor that predisposes to bladder cancer is occupational exposure to carcinogens, namely aromatic amines (benzidine, 4-aminobiphenyl, 2-naphthylamine, 4-chloro-o-toluidine), polycyclic aromatic hydrocarbons, and chlorinated hydrocarbons, which contribute to approximately 20% of all bladder cancers.14-16 Occupational exposure accounts for 25% of bladder cancer diagnoses in men and 11% in women.17

There are several other well-documented risk factors. Pelvic radiation for other malignancies increases the likelihood of developing bladder cancer with a hazard ratio (HR) of 1.7.18 In addition, exposure to S. haematobium infection is predominantly associated with an increased risk of squamous cell carcinoma of the bladder and is a significant clinical problem in many developing nations. This disease process is a much less common entity in the United States and not the major focus of this report.

Genetic predisposition to bladder cancer has been linked to genes involved in metabolism of carcinogens such as N-acetyl transferase and GSTM1-null genotypes.19 Large genome-wide association studies have also found sequence variants that can increase the risk for bladder cancer, such as subjects with urea transporter gene SLC14A that is associated with renal urine concentration, and thus with variations in contact of carcinogens with urothelial surfaces.20-24

Urothelial carcinoma is often multifocal with a high rate of recurrence; the exact etiology of this characteristic is currently unknown. Two of the most commonly held theories: 1) a genetic field defect exists with multiple new tumors spontaneously arising or, 2) the local reimplantation of tumor cells occurs with tumor resection. Evidence suggests that tumor reimplantation or submucosal migration may be early mechanisms for multifocality.25 Multifocal tumors as well as upper tract and lower tract lesions arising in one individual may demonstrate clonality.26

Prognosis

The overall prognosis of patients with MIBC has not changed in the last 30 years. In patients who undergo cystectomy, systemic recurrence rates vary by stage, but range from 20-30% for pathologic stage pT2, 40% for pT3, >50% for pT4 and approximately 70% for node-positive disease.27, 28 Most recurrences will occur within the first two to three years after cystectomy, and at this time, most patients with recurrence after cystectomy are not cured with current systemic therapies.29

A pooled analysis of multiple prospective Radiation Therapy Oncology Group (RTOG) protocols evaluating bladder preserving combined-modality therapy for MIBC with a median follow up of 4.3 years found the 5- and 10-year overall survival rates were 57% and 36%, respectively, and the 5- and 10-year disease specific survival rates were 71% and 65%, respectively.30

The dominant pathologic predictors for recurrence and survival are tumor stage and nodal status. Other prognostic factors include gender, presence of hydronephrosis, lymphovascular invasion, soft tissue margin status, and molecular subtyping characteristics.31-36 Variant histology has become better described and recognized, and the treatment for these cancers may vary from conventional urothelial carcinoma. There is also a significant impact of treatment choices on outcome with the type and timing of therapy playing an important role.37, 38

Scope

This evidence-based guideline for clinically non-metastatic muscle-invasive urothelial bladder cancer (cT2-T4N0M0) focuses on the evaluation, treatment, and surveillance of MIBC and is guided toward curative intent. The treatment of patients with clinically evident metastatic bladder cancer is outside the context of this guideline and will not be discussed. Optimal initial evaluation of patients with MIBC, including imaging and proper staging, are discussed. The role of radical cystectomy and bilateral pelvic lymphadenectomy is defined. Bladder preserving regimens such as a multi-modal approach that combines maximal TURBT, chemotherapy and radiation therapy as well as partial cystectomy, radiation alone and maximal TURBT alone, are assessed.

In addition, this guideline will discuss QOL aspects of care and the importance of careful patient counseling. The guidelines will also address timing and mode of testing used in surveillance of disease. Finally, there will be a section devoted to variant histology and the current unique aspects of care for certain non-urothelial cancers of the bladder.

GUIDELINE STATEMENTS

Initial Patient Evaluation & Counseling

Guideline Statement 1

Prior to treatment consideration, a full history and physical exam should be performed, including an exam under anesthesia, at the time of transurethral resection of bladder tumor (TURBT) for a suspected invasive cancer. (Clinical Principle)

Discussion


Guideline Statement 2

Prior to muscle-invasive bladder cancer management, clinicians should perform a complete staging evaluation, including imaging of the chest and cross sectional imaging of the abdomen and pelvis with intravenous contrast if not contraindicated. Laboratory evaluation should include a comprehensive metabolic panel (complete blood count, liver function tests, alkaline phosphatase, and renal function). (Clinical Principle)

Discussion


Guideline Statement 3

An experienced genitourinary pathologist should review the pathology of a patient when variant histology is suspected or if muscle invasion is equivocal (e.g., micropapillary, nested, plasmacytoid, neuroendocrine, sarcomatoid, extensive squamous or glandular differentiation). (Clinical Principle)

Discussion


Guideline Statement 4

For patients with newly diagnosed muscle-invasive bladder cancer, curative treatment options should be discussed before determining a plan of therapy that is based on both patient comorbidity and tumor characteristics. Patient evaluation should be completed using a multidisciplinary approach. (Clinical Principle)

Discussion


Guideline Statement 5

Prior to treatment, clinicians should counsel patients regarding complications and the implications of treatment on QOL (e.g., impact on continence, sexual function, fertility, bowel dysfunction, metabolic problems). (Clinical Principle)

Discussion


Treatment

Neoadjuvant/Adjuvant Chemotherapy

Guideline Statement 6

Utilizing a multidisciplinary approach, clinicians should offer cisplatin-based neoadjuvant chemotherapy (NAC) to eligible radical cystectomy patients prior to cystectomy. (Strong Recommendation; Evidence Level: Grade B)

Discussion


Guideline Statement 7

Clinicians should not prescribe carboplatin-based NAC for clinically resectable stage cT2-T4aN0 bladder cancer. Patients ineligible for cisplatin-based NAC should proceed to definitive locoregional therapy or clinical trial. (Expert Opinion)

Discussion


Guideline Statement 8

Clinicians should perform radical cystectomy as soon as possible following a patient’s completion of and recovery from NAC (ideally within 12 weeks unless medically inadvisable). (Expert Opinion)

Discussion


Guideline Statement 9

Patients who have not received cisplatin-based NAC and have pT3-4and/or N+ disease at cystectomy should be offered adjuvant cisplatin-based chemotherapy or adjuvant immunotherapy. Patients who have received cisplatin-based chemotherapy and have pT2-4and/or N+ at cystectomy should be offered adjuvant immunotherapy. (Moderate Recommendation; Evidence Level: Grade C)

Discussion


Radical Cystectomy

Guideline Statement 10

Clinicians should offer radical cystectomy with bilateral pelvic lymphadenectomy for surgically eligible patients with resectable non-metastatic (M0) muscle-invasive bladder cancer. (Strong Recommendation; Evidence Level: Grade B)

Discussion


Guideline Statement 11

When performing a standard radical cystectomy with curative intent, clinicians should remove the bladder, prostate, and seminal vesicles in males; clinicians should remove the bladder in females and should consider removal of adjacent reproductive organs based on individual disease characteristics and need to obtain negative margins. Organ sparing procedures in females should be considered based on disease location and characteristics on an individual basis. (Clinical Principle)

Discussion


Guideline Statement 12

Clinicians should discuss and consider sexual function preserving procedures for patients with organ-confined disease and absence of bladder neck, urethra, and prostate (male) involvement. (Moderate Recommendation; Evidence Level: Grade C)

Discussion


Urinary Diversion

Guideline Statement 13

In patients undergoing radical cystectomy, ileal conduit, continent cutaneous, and orthotopic neobladder urinary diversions should all be discussed. (Clinical Principle)

Discussion


Guideline Statement 14

In patients receiving an orthotopic urinary diversion, clinicians must verify a negative urethral margin. (Clinical Principle)

Discussion


Perioperative Surgical Management

Guideline Statement 15

Clinicians should attempt to optimize patient performance status (PS) in the perioperative setting. (Expert Opinion)

Discussion


Guideline Statement 16

Perioperative pharmacologic thromboembolic prophylaxis should be given to patients undergoing radical cystectomy. (Strong Recommendation; Evidence Level: Grade B)

Discussion


Guideline Statement 17

In patients undergoing radical cystectomy µ -opioid antagonist therapy should be used to accelerate gastrointestinal recovery, unless contraindicated. (Strong Recommendation; Evidence Level: Grade B)

Discussion


Guideline Statement 18

Patients should receive detailed teaching regarding care of urinary diversion prior to discharge from the hospital. (Clinical Principle)

Discussion


Pelvic Lymphadenectomy

Guideline Statement 19

Clinicians must perform a bilateral pelvic lymphadenectomy at the time of any surgery with curative intent. (Strong Recommendation; Evidence Level: Grade B)

Discussion


Guideline Statement 20

When performing bilateral pelvic lymphadenectomy, clinicians should remove, at a minimum, the external and internal iliac and obturator lymph nodes (standard lymphadenectomy). (Clinical Principle)

Discussion


Bladder Preserving Approaches

Patient Selection

A multi-modal bladder preserving approach with its merits and disadvantages should be discussed in each individual case. The studies that support bladder preserving strategies generally have highly select patient populations. There are currently no randomized trials comparing NAC and radical cystectomy versus multi-modality bladder preserving therapies. In reviewing the available studies regarding multi-modal bladder preserving protocols that employ TURBT, radiation therapy, and chemotherapy for carefully selected patients, the Panel found no strong evidence to determine whether or not immediate cystectomy improved survival when compared to initial bladder sparing protocols that employ salvage cystectomy as therapy for persistent bladder cancer.126-132, 134 In addition, no high quality evidence directly compares QOL between the different treatment options; instead a number of studies report on health-related QOL outcomes and draw comparisons to other therapies. The Panel also recognizes that other non-multi-modal bladder–preserving regimens, although having less oncologic efficacy as well as less data, do exist and may be a reasonable option for certain patients, especially those who have poorer PS.

Guideline Statement 21

For patients with newly diagnosed non-metastatic muscle-invasive bladder cancer who desire to retain their bladder, and for those with significant comorbidities for whom radical cystectomy is not a treatment option, clinicians should offer bladder preserving therapy when clinically appropriate. (Clinical Principle)

Discussion


Guideline Statement 22

In patients under consideration for bladder preserving therapy, maximal debulking TURBT and assessment of multifocal disease/carcinoma in situ (CIS) should be performed. (Strong Recommendation; Evidence Level: Grade C)

Discussion


Maximal TURBT and Partial Cystectomy

Guideline Statement 23

Patients with muscle-invasive bladder cancer who are medically fit and consent to radical cystectomy should not undergo partial cystectomy or maximal TURBT as primary curative therapy. (Moderate Recommendation; Evidence Level: Grade C)

Discussion


Primary Radiation Therapy

Guideline Statement 24

For patients with muscle-invasive bladder cancer, clinicians should not offer radiation therapy alone as a curative treatment. (Strong Recommendation; Evidence Level: Grade C)

Discussion


Multi-Modal Bladder Preserving Therapy

Guideline Statement 25

For patients with muscle-invasive bladder cancer who have elected tri-modality therapy with organ preservation, clinicians should offer maximal TURBT followed by chemotherapy combined with external beam radiation therapy (EBRT). Planned cystoscopic surveillance per high-risk NMIBC schedule should be performed. (Strong Recommendation; Evidence Level: Grade B)

Discussion


Guideline Statement 26

Radiation sensitizing chemotherapy should be included when using multimodal therapy with curative intent. (Strong Recommendation; Evidence Level: Grade B)

Discussion


Guideline Statement 27

Following completion of bladder preserving therapy, clinicians should perform regular surveillance with computed tomography (CT) scans, cystoscopy, and urine cytology. (Strong Recommendation; Evidence Level: Grade C)

Discussion


Bladder Preserving Treatment Failure

Guideline Statement 28

In patients who are medically fit and have residual or recurrent muscle-invasive disease following bladder preserving therapy, clinicians should offer radical cystectomy with bilateral pelvic lymphadenectomy. (Strong Recommendation; Evidence Level: Grade C)

Discussion


Guideline Statement 29

In patients who have a non-muscle invasive recurrence after bladder preserving therapy, clinicians may offer either local measures, such as TURBT with intravesical therapy, or radical cystectomy with bilateral pelvic lymphadenectomy. (Moderate Recommendation; Evidence Level: Grade C)

Discussion


Patient Surveillance & Follow Up

Imaging

Guideline Statement 30

Clinicians should obtain chest imaging and cross sectional imaging of the abdomen and pelvis with CT or magnetic resonance imaging (MRI) at 6-12 month intervals for 2-3 years and then may continue annually. (Expert Opinion)

Discussion


Laboratory Values and Urine Markers

Guideline Statement 31

Following therapy for muscle-invasive bladder cancer, patients should undergo laboratory assessment at three to six month intervals for two to three years and then annually thereafter. (Expert Opinion)

Discussion


Guideline Statement 32

Following radical cystectomy in patients with a retained urethra, clinicians should monitor the urethral remnant for recurrence. (Expert Opinion)

Discussion


Patient Survivorship

Guideline Statement 33

Clinicians should discuss with patients how they are coping with their bladder cancer diagnosis and treatment and should recommend that patients consider participating in a cancer support group or consider receiving individual counseling. (Expert Opinion)

Discussion


Guideline Statement 34

Clinicians should encourage bladder cancer patients to adopt healthy lifestyle habits, including smoking cessation, exercise, and a healthy diet, to improve long-term health and QOL. (Expert Opinion)

Discussion


Variant Histology

Guideline Statement 35

In patients diagnosed with variant histology, clinicians should consider unique clinical characteristics that may require divergence from standard evaluation and management for urothelial carcinoma. (Expert Opinion)

Discussion


FUTURE DIRECTIONS

Several key areas of future research need emphasis to improve clinical care and provide a path to better patient outcomes with invasive bladder cancer.

Detection and markers.  Improved imaging modalities to better locally stage tumors and define extent of disease are needed. This includes cystoscopic and radiographic imaging of local disease and more effective and accurate evaluation techniques of regional lymphatics and distant sites. The role of MRI, vesical imaging-reporting and data system (VI-RADS) for local staging and defining the role of PET imaging, the best PET imaging agent, and the investigation/validation of other novel technologies are deemed high-priority.

Urine cytology can be used to monitor for recurrence after TURBT and cystectomy, but difficulties with interpretation after urinary diversion have limited its usefulness after bladder removal. Radiation therapy can alter the appearance of shed cells and oftentimes result in atypical results. Current urinary markers have a limited role in the routine monitoring for recurrence of urothelial carcinoma after radical cystectomy due to false positive rate. Future studies should focus on the development of urinary and serum-based markers that can be used to identify early urothelial based and/or distant recurrences.

Increased knowledge gained from comprehensive genetic studies of invasive bladder cancer should be utilized to identify and validate markers that could be used to guide diagnosis and therapeutic decision making. This would include the identification of prognostic markers capable of stratifying patients at risk for advanced disease, predictive markers for the response to chemotherapeutic/immunotherapeutic agents as well as radiation-based therapies. In addition, further studies are needed to evaluate and validate the prognostic and predictive information obtained from novel molecular classifications of bladder cancer.

Therapy. The rapid introduction of novel immunotherapeutic agents for treatment of bladder cancer has begun to show promise. Phase II and III studies have now demonstrated significant antitumor activity of the anti-PD-1 and anti-PDL-1 antibodies in the metastatic setting.  Additional studies are needed to further define the role of these agents alone or in combination with other therapies for all stages of bladder cancer.

In addition, further studies are needed to better integrate multi-modal therapy in patients with invasive bladder cancer. Specific examples include the role for AC or immunotherapy in patients who have previously received NAC followed by surgery but still possess high-risk pathology (residual invasive disease or regional lymph node involvement) and the role of immunotherapy in bladder preservation. A phase I trial investigating the addition of concurrent immune-checkpoint inhibition to chemoradiation for bladder preservation in patients with muscle-invasive disease found high rates of metastasis-free and overall survival, and a phase III trial (NCT03775265) investigating the role of atezolizumab with chemoradiation recently completed  enrollment and will provide further data regarding the role of immunotherapy with bladder preservation.291 Additionally, the role of radiation in patients undergoing radical cystectomy for T3 and T4 disease, including the use of intraoperative radiation therapy, is yet to be clearly defined.

Robotic cystectomy has been adopted as a surgical option for the treatment of patients with invasive bladder cancer with the hope that it will improve the morbidity associated with radical cystectomy. RCTs have shown decreased blood loss with robotic cystectomy as compared to open cystectomy with no difference in complications, length of hospitalization, readmission rates, pain, QOL, or postoperative mortality and no difference in short-term progression-free survival.292, 293 Long-term data is needed to demonstrate the oncologic efficacy, potential for improved clinical outcomes, and QOL using this technology compared to standard open techniques.

Tissue regenerative technology continues to advance, stimulating the hope that organ replacement may be available in the future. Support of basic and translational research is needed to move tissue regeneration forward into clinical use for patients who require bladder removal for invasive bladder cancer.

The currently unpublished SWOG S1011 trial compared extended LND with standard LND and found no significant difference in DFS or overall survival.219 However, presentation of unpublished long-term follow-up of the German LEA AUO AB 25/02 trial suggests improvement in survival associated with an extended LND.220

In addition, studies emphasizing PROs after treatment for invasive bladder cancer are needed. This information is necessary to help further support patient centered outcomes and identify specific areas of treatment that require further attention to improve patient QOL.

Surveillance. Finally, the optimal strategies for surveillance after definitive treatment for invasive bladder cancer to identify pelvic, distant, and urothelial recurrences need to be defined. The role of specific imaging tests and laboratory studies as well as their appropriate interval has yet to be established. Some evidence suggests a potential role for circulating tumor cell DNA (ctDNA) in detecting recurrence and progression following radical cystectomy. Future studies are needed to further define the potential role of ctDNA for surveillance.

ABBREVIATIONS

5-FU

5-fluorouracil

AC

Adjuvant chemotherapy

AHRQ

Agency for Healthcare Research and Quality

ASCO

American Society of Clinical Oncology

ASTRO

American Society for Radiation Oncology

AUA

American Urological Association

CIS

Carcinoma in situ

ctDNA

Circulating tumor cell DNA

CI

Confidence interval

CMV

Cisplatin, methotrexate and vinblastine

CT

Computed tomography

ddMVAC

Dose-dense methotrexate, vinblastine, Adriamycin, and cisplatin

DFS

Disease free survival

EBRT

External beam radiation therapy

GC

Gemcitabine and cisplatin

GRADE

Grading of Recommendations Assessment, Development, and Evaluation

HR

Hazard ratio

LND

Lymph node dissection

MIBC

Muscle invasive bladder cancer

MRI

Magnetic resonance imaging

MVAC

Methotrexate, vinblastine, Adriamycin, and cisplatin

NAC

Neoadjuvant chemotherapy

NMIBC

Non-muscle invasive bladder cancer

PGC

Practice Guidelines Committee

PS

Performance status

RCT

Randomized controlled trial

RTOG

Radiation Therapy Oncology Group

SEER

Surveillance, Epidemiology, and End Results

SUO

Society of Urologic Oncology

TURBT

Transurethral resection of bladder tumor

QOL

Quality of life

VI-RADS

Vesical imaging-reporting and data system

Tools and Resources

REFERENCES

  1. Chou, R., Buckley, D., Fu, R. et al: Ahrq comparative effectiveness reviews. In: Emerging approaches to diagnosis and treatment of non–muscle-invasive bladder cancer. Rockville (MD): Agency for Healthcare Research and Quality (US), 2015
  2. U.S. Preventive services task force procedure manual: AHRQ Publication No. 08-05118- EF, 2008
  3. Methods guide for effectiveness and comparative effectiveness reviews. Agency for healthcare research and quality. Rockville, MD, 2014
  4. Guyatt G, Oxman AD, Akl EA et al: Grade guidelines: 1. Introduction-grade evidence profiles and summary of findings tables. J Clin Epidemiol 2011; 64: 383.
  5. Hsu, C.-C.: Practical assessment, research, and evaluation practical assessment, research, and evaluation. 2007, 12:1.
  6. Siegel, R. L., Giaquinto, A. N., and Jemal, A.: Cancer statistics, 2024. CA: A Cancer Journal for Clinicians 2024, 74:12.
  7. Smith, A. B., Deal, A. M., Woods, M. E. et al: Muscle-invasive bladder cancer: Evaluating treatment and survival in the national cancer data base. BJU Int 2014, 114:719.
  8. Burger, M., Catto, J. W., Dalbagni, G. et al: Epidemiology and risk factors of urothelial bladder cancer. Eur Urol 2013, 63:234.
  9. Charlton, M. E., Adamo, M. P., Sun, L. and Deorah, S.: Bladder cancer collaborative stage variables and their data quality, usage, and clinical implications: A review of seer data, 2004-2010. Cancer 2014, 120 Suppl 23:3815.
  10. Siegel, R. L., Miller, K. D. and Jemal, A.: Cancer statistics, 2017. CA Cancer J Clin 2017, 67:7.
  11. Freedman, N. D., Silverman, D. T., Hollenbeck, A. R. et al: Association between smoking and risk of bladder cancer among men and women. Jama 2011, 306:737.
  12. Samanic, C., Kogevinas, M., Dosemeci, M. et al: Smoking and bladder cancer in spain: Effects of tobacco type, timing, environmental tobacco smoke, and gender. Cancer Epidemiol Biomarkers Prev 2006, 15:1348.
  13. Jiang, X., Yuan, J. M., Skipper, P. L. et al: Environmental tobacco smoke and bladder cancer risk in never smokers of los angeles county. Cancer Res 2007, 67:7540.
  14. Rushton, L., Bagga, S., Bevan, R. et al: Occupation and cancer in britain. Br J Cancer 2010, 102:1428.
  15. Samanic, C. M., Kogevinas, M., Silverman, D. T. et al: Occupation and bladder cancer in a hospital-based case-control study in spain. Occup Environ Med 2008, 65:347.
  16. Koutros, S., Silverman, D. T., Baris, D. et al: Hair dye use and risk of bladder cancer in the new england bladder cancer study. Int J Cancer 2011, 129:2894.
  17. Poel, H., Mungan, N. and Witjes, J.: Bladder cancer in women. International urogynecology journal and pelvic floor dysfunction 1999, 10:207.
  18. Abern, M. R., Dude, A. M., Tsivian, M. and Coogan, C. L.: The characteristics of bladder cancer after radiotherapy for prostate cancer. Urol Oncol 2013, 31:1628.
  19. An, Y., Li, H., Wang, K. J. et al: Meta-analysis of the relationship between slow acetylation of n-acetyl transferase 2 and the risk of bladder cancer. Genet Mol Res 2015, 14:16896.
  20. Guey, L. T., García-Closas, M., Murta-Nascimento, C. et al: Genetic susceptibility to distinct bladder cancer subphenotypes. Eur Urol 2010, 57:283.
  21. Kiemeney, L. A., Sulem, P., Besenbacher, S. et al: A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer. Nat Genet 2010, 42:415.
  22. Kiemeney, L. A., Thorlacius, S., Sulem, P. et al: Sequence variant on 8q24 confers susceptibility to urinary bladder cancer. Nat Genet 2008, 40:1307.
  23. Rothman, N., Garcia-Closas, M., Chatterjee, N. et al: A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci. Nat Genet 2010, 42:978.
  24. Wu, X., Ye, Y. and Kiemeney, L. A.: A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci. Nat Genet 2009, 41:991.
  25. Bryan, R. T., Collins, S. I., Daykin, M. C. et al: Mechanisms of recurrence of ta/t1 bladder cancer. Ann R Coll Surg Engl 2010, 92:519.
  26. Lamy, P., Nordentoft, I., Birkenkamp-Demtröder, K. et al: Paired exome analysis reveals clonal evolution and potential therapeutic targets in urothelial carcinoma. Cancer Res 2016, 76:5894.
  27. Karakiewicz, P. I., Shariat, S. F., Palapattu, G. S. et al: Nomogram for predicting disease recurrence after radical cystectomy for transitional cell carcinoma of the bladder. J Urol 2006, 176:1354.
  28. Bochner, B. H., Kattan, M. W. and Vora, K. C.: Postoperative nomogram predicting risk of recurrence after radical cystectomy for bladder cancer. J Clin Oncol 2006, 24:3967.
  29. Seisen, T., Sun, M., Leow, J. J. et al: Efficacy of high-intensity local treatment for metastatic urothelial carcinoma of the bladder: A propensity score-weighted analysis from the national cancer data base. J Clin Oncol 2016, 34:3529.
  30. Mak, R. H., Hunt, D., Shipley, W. U. et al: Long-term outcomes in patients with muscle-invasive bladder cancer after selective bladder-preserving combined-modality therapy: A pooled analysis of radiation therapy oncology group protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol 2014, 32:3801.
  31. Dobruch, J., Daneshmand, S., Fisch, M. et al: Gender and bladder cancer: A collaborative review of etiology, biology, and outcomes. Eur Urol 2016, 69:300.
  32. Lotan, Y., Gupta, A., Shariat, S. F. 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. J Clin Oncol 2005, 23:6533.
  33. Choi, W., Czerniak, B., Ochoa, A. et al: Intrinsic basal and luminal subtypes of muscle-invasive bladder cancer. Nat Rev Urol 2014, 11:400.
  34. Xylinas, E., Rink, M., Novara, G. et al: Predictors of survival in patients with soft tissue surgical margin involvement at radical cystectomy. Ann Surg Oncol 2013, 20:1027.
  35. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 2014, 507:315.
  36. Sjödahl, G., Lauss, M., Lövgren, K. et al: A molecular taxonomy for urothelial carcinoma. Clin Cancer Res 2012, 18:3377.
  37. Choi, W., Porten, S., Kim, S. et al: Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell 2014, 25:152.
  38. Damrauer, J. S., Hoadley, K. A., Chism, D. D. et al: Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology. Proc Natl Acad Sci U S A 2014, 111:3110.
  39. Koppie, T. M., Serio, A. M., Vickers, A. J. et al: Age-adjusted charlson comorbidity score is associated with treatment decisions and clinical outcomes for patients undergoing radical cystectomy for bladder cancer. Cancer 2008, 112:2384.
  40. Lotan, Y., Amiel, G., Boorjian, S. A. et al: Comprehensive handbook for developing a bladder cancer cystectomy database. Urol Oncol 2013, 31:812.
  41. Marshall, V. F.: The relation of the preoperative estimate to the pathologic demonstration of the extent of vesical neoplasms. J Urol 1952, 68:714.
  42. Culp, S. H., Dickstein, R. J., Grossman, H. B. et al: Refining patient selection for neoadjuvant chemotherapy before radical cystectomy. J Urol 2014, 191:40.
  43. Husband, J. E., Olliff, J. F., Williams, M. P. et al: Bladder cancer: Staging with ct and mr imaging. Radiology 1989, 173:435.
  44. Vargas, H. A., Akin, O., Schöder, H. et al: Prospective evaluation of mri, ¹¹c-acetate pet/ct and contrast-enhanced ct for staging of bladder cancer. Eur J Radiol 2012, 81:4131.
  45. Moyer, V. A.: Screening for lung cancer: U.S. Preventive services task force recommendation statement. Ann Intern Med 2014, 160:330.
  46. Braendengen, M., Winderen, M. and Fosså, S. D.: Clinical significance of routine pre-cystectomy bone scans in patients with muscle-invasive bladder cancer. Br J Urol 1996, 77:36.
  47. Aljabery, F., Lindblom, G., Skoog, S. et al: Pet/ct versus conventional ct for detection of lymph node metastases in patients with locally advanced bladder cancer. BMC Urol 2015, 15:87.
  48. Jeong, I. G., Hong, S., You, D. et al: Fdg pet-ct for lymph node staging of bladder cancer: A prospective study of patients with extended pelvic lymphadenectomy. Ann Surg Oncol 2015, 22:3150.
  49. Kibel, A. S., Dehdashti, F., Katz, M. D. et al: Prospective study of [18f]fluorodeoxyglucose positron emission tomography/computed tomography for staging of muscle-invasive bladder carcinoma. J Clin Oncol 2009, 27:4314.
  50. Sangoi, A. R., Beck, A. H., Amin, M. B. et al: Interobserver reproducibility in the diagnosis of invasive micropapillary carcinoma of the urinary tract among urologic pathologists. Am J Surg Pathol 2010, 34:1367.
  51. Linder, B. J., Boorjian, S. A., Cheville, J. C. et al: The impact of histological reclassification during pathology re-review--evidence of a will rogers effect in bladder cancer? J Urol 2013, 190:1692.
  52. Hansel, D. E., Amin, M. B., Comperat, E. et al: A contemporary update on pathology standards for bladder cancer: Transurethral resection and radical cystectomy specimens. European urology 2013, 63:321.
  53. Kim, S. P., Frank, I., Cheville, J. C. et al: The impact of squamous and glandular differentiation on survival after radical cystectomy for urothelial carcinoma. J Urol 2012, 188:405.
  54. Linder, B. J., Frank, I., Cheville, J. C. et al: Outcomes following radical cystectomy for nested variant of urothelial carcinoma: A matched cohort analysis. J Urol 2013, 189:1670.
  55. Wang, J. K., Boorjian, S. A., Cheville, J. C. et al: Outcomes following radical cystectomy for micropapillary bladder cancer versus pure urothelial carcinoma: A matched cohort analysis. World J Urol 2012, 30:801.
  56. Kassouf, W., Spiess, P. E., Brown, G. A. et al: Prostatic urethral biopsy has limited usefulness in counseling patients regarding final urethral margin status during orthotopic neobladder reconstruction. J Urol 2008, 180:164.
  57. Psutka, S. P., Carrasco, A., Schmit, G. D. et al: Sarcopenia in patients with bladder cancer undergoing radical cystectomy: Impact on cancer-specific and all-cause mortality. Cancer 2014, 120:2910.
  58. Carli, F., Awasthi, R., Gillis, C. and Kassouf, W.: Optimizing a frail elderly patient for radical cystectomy with a prehabilitation program. Can Urol Assoc J 2014, 8:E884.
  59. Chhabra, K. R., Sacks, G. D. and Dimick, J. B.: Surgical decision making: Challenging dogma and incorporating patient preferences. Jama 2017, 317:357.
  60. Rammant, E., Fox, L., Beyer, K. et al: The current use of the eortc qlq-nmibc24 and qlq-blm30 questionnaires for the assessment of health-related quality of life in bladder cancer patients: A systematic review. Qual Life Res 2023, 32:2127.
  61. Blazeby, J. M., Hall, E., Aaronson, N. K. et al: Validation and reliability testing of the eortc qlq-nmibc24 questionnaire module to assess patient-reported outcomes in non-muscle-invasive bladder cancer. Eur Urol 2014, 66:1148.
  62. Anderson, C. B., Feurer, I. D., Large, M. C. et al: Psychometric characteristics of a condition-specific, health-related quality-of-life survey: The fact-vanderbilt cystectomy index. Urology 2012, 80:77.
  63. Gilbert, S. M., Dunn, R. L., Hollenbeck, B. K. 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. J Urol 2010, 183:1764.
  64. Danna, B. J., Metcalfe, M. J., Wood, E. L. and Shah, J. B.: Assessing symptom burden in bladder cancer: An overview of bladder cancer specific health-related quality of life instruments. Bladder Cancer 2016, 2:329.
  65. Siegrist, T., Savage, C., Shabsigh, A. et al: Analysis of gender differences in early perioperative complications following radical cystectomy at a tertiary cancer center using a standardized reporting methodology. Urol Oncol 2010, 28:112.
  66. Froehner, M., Brausi, M. A., Herr, H. W. et al: Complications following radical cystectomy for bladder cancer in the elderly. Eur Urol 2009, 56:443.
  67. Quek, M. L., Stein, J. P., Daneshmand, S. et al: A critical analysis of perioperative mortality from radical cystectomy. J Urol 2006, 175:886.
  68. Novara, G., Catto, J. W., Wilson, T. et al: Systematic review and cumulative analysis of perioperative outcomes and complications after robot-assisted radical cystectomy. Eur Urol 2015, 67:376.
  69. Bream, M. J., Maurice, M. J., Altschuler, J. et al: Increased use of cystectomy in patients 75 and older: A contemporary analysis of survival and perioperative outcomes from the national cancer database. Urology 2017, 100:72.
  70. Djaladat, H., Katebian, B., Bazargani, S. T. et al: 90-day complication rate in patients undergoing radical cystectomy with enhanced recovery protocol: A prospective cohort study. World J Urol 2017, 35:907.
  71. Chappidi, M. R., Kates, M., Stimson, C. J. et al: Causes, timing, hospital costs and perioperative outcomes of index vs nonindex hospital readmissions after radical cystectomy: Implications for regionalization of care. J Urol 2017, 197:296.
  72. Hu, M., Jacobs, B. L., Montgomery, J. S. et al: Sharpening the focus on causes and timing of readmission after radical cystectomy for bladder cancer. Cancer 2014, 120:1409.
  73. Bochner, B. H., Dalbagni, G., Sjoberg, D. D. et al: Comparing open radical cystectomy and robot-assisted laparoscopic radical cystectomy: A randomized clinical trial. Eur Urol 2015, 67:1042.
  74. Murthy, V., Masodkar, R., Kalyani, N. et al: Clinical outcomes with dose-escalated adaptive radiation therapy for urinary bladder cancer: A prospective study. Int J Radiat Oncol Biol Phys 2016, 94:60.
  75. Zietman, A. L., Sacco, D., Skowronski, U. 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. J Urol 2003, 170:1772.
  76. Lee, R. K., Abol-Enein, H., Artibani, W. et al: Urinary diversion after radical cystectomy for bladder cancer: Options, patient selection, and outcomes. BJU Int 2014, 113:11.
  77. Gross, T., Meierhans Ruf, S. D., Meissner, C. et al: Orthotopic ileal bladder substitution in women: Factors influencing urinary incontinence and hypercontinence. Eur Urol 2015, 68:664.
  78. Hautmann, R. E., de Petriconi, R. C. and Volkmer, B. G.: Lessons learned from 1,000 neobladders: The 90-day complication rate. J Urol 2010, 184:990.
  79. Studer, U. E., Burkhard, F. C., Schumacher, M. et al: Twenty years experience with an ileal orthotopic low pressure bladder substitute--lessons to be learned. J Urol 2006, 176:161.
  80. Ali-el-Dein, B., Shaaban, A. A., Abu-Eideh, R. H. et al: Surgical complications following radical cystectomy and orthotopic neobladders in women. J Urol 2008, 180:206.
  81. Ahmadi, H., Skinner, E. C., Simma-Chiang, V. et al: Urinary functional outcome following radical cystoprostatectomy and ileal neobladder reconstruction in male patients. J Urol 2013, 189:1782.
  82. Hautmann, R. E., Paiss, T. and de Petriconi, R.: The ileal neobladder in women: 9 years of experience with 18 patients. J Urol 1996, 155:76.
  83. Hautmann, R. E., de Petriconi, R., Kleinschmidt, K. et al: Orthotopic ileal neobladder in females: Impact of the urethral resection line on functional results. Int Urogynecol J Pelvic Floor Dysfunct 2000, 11:224.
  84. Stein, J. P., Ginsberg, D. A. and Skinner, D. G.: Indications and technique of the orthotopic neobladder in women. Urol Clin North Am 2002, 29:725.
  85. Bartsch, G., Daneshmand, S., Skinner, E. C. et al: Urinary functional outcomes in female neobladder patients. World J Urol 2014, 32:221.
  86. Colombo, R., Pellucchi, F., Moschini, M. et al: Fifteen-year single-centre experience with three different surgical procedures of nerve-sparing cystectomy in selected organ-confined bladder cancer patients. World J Urol 2015, 33:1389.
  87. Zahran, M. H., Fahmy, O., El-Hefnawy, A. S. and Ali-El-Dein, B.: Female sexual dysfunction post radical cystectomy and urinary diversion. Climacteric 2016, 19:546.
  88. Feuerstein, M. A. and Goenka, A.: Quality of life outcomes for bladder cancer patients undergoing bladder preservation with radiotherapy. Curr Urol Rep 2015, 16:75.
  89. Eisenberg, M. S., Thompson, R. H., Frank, I. et al: Long-term renal function outcomes after radical cystectomy. J Urol 2014, 191:619.
  90. Gupta, A., Atoria, C. L., Ehdaie, B. et al: Risk of fracture after radical cystectomy and urinary diversion for bladder cancer. J Clin Oncol 2014, 32:3291.
  91. Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: A randomised controlled trial. International collaboration of trialists. Lancet 1999, 354:533.
  92. Griffiths, G., Hall, R., Sylvester, R. et al: International phase iii trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: Long-term results of the ba06 30894 trial. J Clin Oncol 2011, 29:2171.
  93. Grossman, H. B., Natale, R. B., Tangen, C. M. et al: Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 2003, 349:859.
  94. Malmström, P. U., Rintala, E., Wahlqvist, R. et al: Five-year followup of a prospective trial of radical cystectomy and neoadjuvant chemotherapy: Nordic cystectomy trial i. The nordic cooperative bladder cancer study group. J Urol 1996, 155:1903.
  95. Rintala, E., Hannisdahl, E., Fosså, S. D. et al: Neoadjuvant chemotherapy in bladder cancer: A randomized study. Nordic cystectomy trial i. Scand J Urol Nephrol 1993, 27:355.
  96. Sengeløv, L., von der Maase, H., Lundbeck, F. et al: Neoadjuvant chemotherapy with cisplatin and methotrexate in patients with muscle-invasive bladder tumours. Acta Oncol 2002, 41:447.
  97. Sherif, A., Rintala, E., Mestad, O. et al: Neoadjuvant cisplatin-methotrexate chemotherapy for invasive bladder cancer -- nordic cystectomy trial 2. Scand J Urol Nephrol 2002, 36:419.
  98. Plimack, E. R., Hoffman-Censits, J. H., Viterbo, R. 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. J Clin Oncol 2014, 32:1895.
  99. Choueiri, T. K., Jacobus, S., Bellmunt, J. et al: Neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin with pegfilgrastim support in muscle-invasive urothelial cancer: Pathologic, radiologic, and biomarker correlates. J Clin Oncol 2014, 32:1889.
  100. Bamias, A., Dafni, U., Karadimou, A. 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). Ann Oncol 2013, 24:1011.
  101. Sternberg, C. N., de Mulder, P., Schornagel, J. H. 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. Eur J Cancer 2006, 42:50.
  102. Sternberg, C. N., de Mulder, P. H., Schornagel, J. H. et al: Randomized phase iii trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (mvac) chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic mvac in advanced urothelial tract tumors: European organization for research and treatment of cancer protocol no. 30924. J Clin Oncol 2001, 19:2638.
  103. Stadler, W. M., Lerner, S. P., Groshen, S. et al: Phase iii study of molecularly targeted adjuvant therapy in locally advanced urothelial cancer of the bladder based on p53 status. J Clin Oncol 2011, 29:3443.
  104. Van Allen, E. M., Mouw, K. W., Kim, P. et al: Somatic ercc2 mutations correlate with cisplatin sensitivity in muscle-invasive urothelial carcinoma. Cancer Discov 2014, 4:1140.
  105. Lee, J. K., Havaleshko, D. M., Cho, H. et al: A strategy for predicting the chemosensitivity of human cancers and its application to drug discovery. Proc Natl Acad Sci U S A 2007, 104:13086.
  106. Plimack, E. R., Dunbrack, R. L., Brennan, T. A. et al: Defects in DNA repair genes predict response to neoadjuvant cisplatin-based chemotherapy in muscle-invasive bladder cancer. Eur Urol 2015, 68:959.
  107. Pfister, C., Gravis, G., Flechon, A. et al: Perioperative dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin in muscle-invasive bladder cancer (vesper): Survival endpoints at 5 years in an open-label, randomised, phase 3 study. Lancet Oncol 2024, 25:255.
  108. Boeri, L., Soligo, M., Frank, I. 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. World J Urol 2019, 37:2409.
  109. Galsky, M. D., Hahn, N. M., Rosenberg, J. et al: A consensus definition of patients with metastatic urothelial carcinoma who are unfit for cisplatin-based chemotherapy. Lancet Oncol 2011, 12:211.
  110. Koie, T., Ohyama, C., Yamamoto, H. et al: Neoadjuvant gemcitabine and carboplatin followed by immediate cystectomy may be associated with a survival benefit in patients with clinical t2 bladder cancer. Med Oncol 2014, 31:949.
  111. Dogliotti, L., Cartenì, G., Siena, S. 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. Eur Urol 2007, 52:134.
  112. Dreicer, R., Manola, J., Roth, B. J. et al: Phase iii trial of methotrexate, vinblastine, doxorubicin, and cisplatin versus carboplatin and paclitaxel in patients with advanced carcinoma of the urothelium. Cancer 2004, 100:1639.
  113. Boeri, L., Soligo, M., Frank, I. et al: Delaying radical cystectomy after neoadjuvant chemotherapy for muscle-invasive bladder cancer is associated with adverse survival outcomes. Eur Urol Oncol 2019, 2:390.
  114. Mmeje, C. O., Benson, C. R., Nogueras-González, G. M. et al: Determining the optimal time for radical cystectomy after neoadjuvant chemotherapy. BJU Int 2018, 122:89.
  115. Freiha, F., Reese, J. and Torti, F. M.: A randomized trial of radical cystectomy versus radical cystectomy plus cisplatin, vinblastine and methotrexate chemotherapy for muscle invasive bladder cancer. J Urol 1996, 155:495.
  116. Cognetti, F., Ruggeri, E. M., Felici, A. 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. Ann Oncol 2012, 23:695.
  117. Skinner, D. G., Daniels, J. R., Russell, C. A. et al: The role of adjuvant chemotherapy following cystectomy for invasive bladder cancer: A prospective comparative trial. J Urol 1991, 145:459.
  118. Bono, A. V., Benvenuti, C., Reali, L. et al: Adjuvant chemotherapy in advanced bladder cancer. Italian uro-oncologic cooperative group. Prog Clin Biol Res 1989, 303:533.
  119. Sternberg, C. N., Skoneczna, I., Kerst, J. M. 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. Lancet Oncol 2015, 16:76.
  120. Leow, J. J., Martin-Doyle, W., Rajagopal, P. S. et al: Adjuvant chemotherapy for invasive bladder cancer: A 2013 updated systematic review and meta-analysis of randomized trials. Eur Urol 2014, 66:42.
  121. Adjuvant chemotherapy in invasive bladder cancer: A systematic review and meta-analysis of individual patient data advanced bladder cancer (abc) meta-analysis collaboration. Eur Urol 2005, 48:189.
  122. Bajorin, D. F., Witjes, J. A., Gschwend, J. E. et al: Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma. N Engl J Med 2021, 384:2102.
  123. Bellmunt, J., Hussain, M., Gschwend, J. E. et al: Adjuvant atezolizumab versus observation in muscle-invasive urothelial carcinoma (imvigor010): A multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 2021, 22:525.
  124. Apolo, A. B., Ballman, K. V., Sonpavde, G. P. et al: Ambassador alliance a031501: Phase iii randomized adjuvant study of pembrolizumab in muscle-invasive and locally advanced urothelial carcinoma (miuc) vs observation. Journal of Clinical Oncology 2024, 42:LBA531.
  125. Witjes, J. A., Compérat, E., Cowan, N. C. et al: Eau guidelines on muscle-invasive and metastatic bladder cancer: Summary of the 2013 guidelines. Eur Urol 2014, 65:778.
  126. Sell, A., Jakobsen, A., Nerstrøm, B. 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. Scand J Urol Nephrol Suppl 1991, 138:193.
  127. Bekelman, J. E., Handorf, E. A., Guzzo, T. et al: Radical cystectomy versus bladder-preserving therapy for muscle-invasive urothelial carcinoma: Examining confounding and misclassification biasin cancer observational comparative effectiveness research. Value Health 2013, 16:610.
  128. Goossens-Laan, C. A., Leliveld, A. M., Verhoeven, R. H. et al: Effects of age and comorbidity on treatment and survival of patients with muscle-invasive bladder cancer. Int J Cancer 2014, 135:905.
  129. Holmäng, S., Hedelin, H., Anderström, C. and Johansson, S. L.: Long-term followup of all patients with muscle invasive (stages t2, t3 and t4) bladder carcinoma in a geographical region. J Urol 1997, 158:389.
  130. Kalogeras, D., Lampri, E., Goussia, A. et al: Radical therapy for muscle-infiltrating bladder cancer (cystectomy or radiotherapy): Does age affect the final therapeutic benefit for the patient? J buon 2008, 13:353.
  131. Kotwal, S., Choudhury, A., Johnston, C. et al: Similar treatment outcomes for radical cystectomy and radical radiotherapy in invasive bladder cancer treated at a united kingdom specialist treatment center. Int J Radiat Oncol Biol Phys 2008, 70:456.
  132. Nieuwenhuijzen, J. A., Pos, F., Moonen, L. M. et al: Survival after bladder-preservation with brachytherapy versus radical cystectomy; a single institution experience. Eur Urol 2005, 48:239.
  133. Rincón Mayans, A., Rosell Costa, D., Zudaire Bergera, J. J. et al: [response and progression-free survival in t2 to t4 bladder tumors treated with trimodality therapy with bladder preservation]. Actas Urol Esp 2010, 34:775.
  134. Solsona, E., Climent, M. A., Iborra, I. 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. Eur Urol 2009, 55:911.
  135. Parekh, D. J., Messer, J., Fitzgerald, J. et al: Perioperative outcomes and oncologic efficacy from a pilot prospective randomized clinical trial of open versus robotic assisted radical cystectomy. J Urol 2013, 189:474.
  136. Messer, J. C., Punnen, S., Fitzgerald, J. et al: Health-related quality of life from a prospective randomised clinical trial of robot-assisted laparoscopic vs open radical cystectomy. BJU Int 2014, 114:896.
  137. Nix, J., Smith, A., Kurpad, R. et al: Prospective randomized controlled trial of robotic versus open radical cystectomy for bladder cancer: Perioperative and pathologic results. Eur Urol 2010, 57:196.
  138. Yuh, B., Wilson, T., Bochner, B. et al: Systematic review and cumulative analysis of oncologic and functional outcomes after robot-assisted radical cystectomy. Eur Urol 2015, 67:402.
  139. Shabsigh, A., Korets, R., Vora, K. C. et al: Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. Eur Urol 2009, 55:164.
  140. Lowrance, W. T., Rumohr, J. A., Chang, S. S. et al: Contemporary open radical cystectomy: Analysis of perioperative outcomes. J Urol 2008, 179:1313.
  141. Stimson, C. J., Chang, S. S., Barocas, D. A. et al: Early and late perioperative outcomes following radical cystectomy: 90-day readmissions, morbidity and mortality in a contemporary series. J Urol 2010, 184:1296.
  142. Gaya, J. M., Matulay, J., Badalato, G. M. et al: The role of preoperative prostatic urethral biopsy in clinical decision-making at the time of radical cystectomy. Can J Urol 2014, 21:7228.
  143. Kates, M., Ball, M. W., Chappidi, M. R. et al: Accuracy of urethral frozen section during radical cystectomy for bladder cancer. Urol Oncol 2016, 34:532.e1.
  144. Schoenberg, M. P., Walsh, P. C., Breazeale, D. R. et al: Local recurrence and survival following nerve sparing radical cystoprostatectomy for bladder cancer: 10-year followup. J Urol 1996, 155:490.
  145. Bhatta Dhar, N., Kessler, T. M., Mills, R. D. et al: Nerve-sparing radical cystectomy and orthotopic bladder replacement in female patients. Eur Urol 2007, 52:1006.
  146. Salem, H. and El-Mazny, A.: Primary and secondary malignant involvement of gynaecological organs at radical cystectomy for bladder cancer: Review of literature and retrospective analysis of 360 cases. J Obstet Gynaecol 2012, 32:590.
  147. Jacobs, B. L., Daignault, S., Lee, C. T. et al: Prostate capsule sparing versus nerve sparing radical cystectomy for bladder cancer: Results of a randomized, controlled trial. J Urol 2015, 193:64.
  148. Hautmann, R. E., Abol-Enein, H., Davidsson, T. et al: Icud-eau international consultation on bladder cancer 2012: Urinary diversion. Eur Urol 2013, 63:67.
  149. Madersbacher, S., Schmidt, J., Eberle, J. M. et al: Long-term outcome of ileal conduit diversion. J Urol 2003, 169:985.
  150. Ghosh, A. and Somani, B. K.: Recent trends in postcystectomy health-related quality of life (qol) favors neobladder diversion: Systematic review of the literature. Urology 2016, 93:22.
  151. Philip, J., Manikandan, R., Venugopal, S. et al: Orthotopic neobladder versus ileal conduit urinary diversion after cystectomy--a quality-of-life based comparison. Ann R Coll Surg Engl 2009, 91:565.
  152. Al Hussein Al Awamlh, B., Wang, L. C., Nguyen, D. P. et al: Is continent cutaneous urinary diversion a suitable alternative to orthotopic bladder substitute and ileal conduit after cystectomy? BJU Int 2015, 116:805.
  153. Chan, Y., Fisher, P., Tilki, D. and Evans, C. P.: Urethral recurrence after cystectomy: Current preventative measures, diagnosis and management. BJU Int 2016, 117:563.
  154. Stein, J. P., Clark, P., Miranda, G. et al: Urethral tumor recurrence following cystectomy and urinary diversion: Clinical and pathological characteristics in 768 male patients. J Urol 2005, 173:1163.
  155. Kanaroglou, A. and Shayegan, B.: Management of the urethra in urothelial bladder cancer. Can Urol Assoc J 2009, 3:S211.
  156. Wu, S. D., Simma-Chang, V. and Stein, J. P.: Pathologic guidelines for orthotopic urinary diversion in women with bladder cancer: A review of the literature. Rev Urol 2006, 8:54.
  157. Lebret, T., Hervé, J. M., Barré, P. et al: Urethral recurrence of transitional cell carcinoma of the bladder. Predictive value of preoperative latero-montanal biopsies and urethral frozen sections during prostatocystectomy. Eur Urol 1998, 33:170.
  158. Stein, J. P., Penson, D. F., Wu, S. D. and Skinner, D. G.: Pathological guidelines for orthotopic urinary diversion in women with bladder cancer: A review of the literature. J Urol 2007, 178:756.
  159. Chen, M. E., Pisters, L. L., Malpica, A. 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. J Urol 1997, 157:2120.
  160. Collins, J. W., Patel, H., Adding, C. et al: Enhanced recovery after robot-assisted radical cystectomy: Eau robotic urology section scientific working group consensus view. Eur Urol 2016, 70:649.
  161. Karl, A., Staehler, M., Bauer, R. et al: Malnutrition and clinical outcome in urological patients. Eur J Med Res 2011, 16:469.
  162. Gregg, J. R., Cookson, M. S., Phillips, S. et al: Effect of preoperative nutritional deficiency on mortality after radical cystectomy for bladder cancer. J Urol 2011, 185:90.
  163. Hemal, S., Krane, L. S., Richards, K. A. et al: Risk factors for infectious readmissions following radical cystectomy: Results from a prospective multicenter dataset. Ther Adv Urol 2016, 8:167.
  164. Crivelli, J. J., Xylinas, E., Kluth, L. A. et al: Effect of smoking on outcomes of urothelial carcinoma: A systematic review of the literature. Eur Urol 2014, 65:742.
  165. Cumberbatch, M. G., Rota, M., Catto, J. W. and La Vecchia, C.: The role of tobacco smoke in bladder and kidney carcinogenesis: A comparison of exposures and meta-analysis of incidence and mortality risks. Eur Urol 2016, 70:458.
  166. Güenaga, K. F., Matos, D. and Wille-Jørgensen, P.: Mechanical bowel preparation for elective colorectal surgery. Cochrane Database Syst Rev 2011, 2011:Cd001544.
  167. Contant, C. M., Hop, W. C., van't Sant, H. P. et al: Mechanical bowel preparation for elective colorectal surgery: A multicentre randomised trial. Lancet 2007, 370:2112.
  168. Kiran, R. P., Murray, A. C., Chiuzan, C. et al: Combined preoperative mechanical bowel preparation with oral antibiotics significantly reduces surgical site infection, anastomotic leak, and ileus after colorectal surgery. Ann Surg 2015, 262:416.
  169. Morris, M. S., Graham, L. A., Chu, D. I. et al: Oral antibiotic bowel preparation significantly reduces surgical site infection rates and readmission rates in elective colorectal surgery. Ann Surg 2015, 261:1034.
  170. Hashad, M. M., Atta, M., Elabbady, A. et al: Safety of no bowel preparation before ileal urinary diversion. BJU Int 2012, 110:E1109.
  171. Large, M. C., Kiriluk, K. J., DeCastro, G. J. et al: The impact of mechanical bowel preparation on postoperative complications for patients undergoing cystectomy and urinary diversion. J Urol 2012, 188:1801.
  172. Gustafsson, U. O., Scott, M. J., Schwenk, W. et al: Guidelines for perioperative care in elective colonic surgery: Enhanced recovery after surgery (eras(®)) society recommendations. World J Surg 2013, 37:259.
  173. Bilku, D. K., Dennison, A. R., Hall, T. C. et al: Role of preoperative carbohydrate loading: A systematic review. Ann R Coll Surg Engl 2014, 96:15.
  174. Carson, J. L., Grossman, B. J., Kleinman, S. et al: Red blood cell transfusion: A clinical practice guideline from the aabb*. Ann Intern Med 2012, 157:49.
  175. Linder, B. J., Frank, I., Cheville, J. C. et al: The impact of perioperative blood transfusion on cancer recurrence and survival following radical cystectomy. Eur Urol 2013, 63:839.
  176. Morgan, T. M., Barocas, D. A., Chang, S. S. et al: The relationship between perioperative blood transfusion and overall mortality in patients undergoing radical cystectomy for bladder cancer. Urol Oncol 2013, 31:871.
  177. Chalfin, H. J., Liu, J. J., Gandhi, N. et al: Blood transfusion is associated with increased perioperative morbidity and adverse oncologic outcomes in bladder cancer patients receiving neoadjuvant chemotherapy and radical cystectomy. Ann Surg Oncol 2016, 23:2715.
  178. Xu, W., Daneshmand, S., Bazargani, S. T. et al: Postoperative pain management after radical cystectomy: Comparing traditional versus enhanced recovery protocol pathway. J Urol 2015, 194:1209.
  179. Forrest, J. B., Clemens, J. Q., Finamore, P. et al: Aua best practice statement for the prevention of deep vein thrombosis in patients undergoing urologic surgery. J Urol 2009, 181:1170.
  180. Collins, R., Scrimgeour, A., Yusuf, S. and Peto, R.: 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. N Engl J Med 1988, 318:1162.
  181. Bergqvist, D.: Low molecular weight heparin for the prevention of venous thromboembolism after abdominal surgery. Br J Surg 2004, 91:965.
  182. Geerts, W. H., Bergqvist, D., Pineo, G. F. et al: Prevention of venous thromboembolism: American college of chest physicians evidence-based clinical practice guidelines (8th edition). Chest 2008, 133:381s.
  183. Jacobs, J. J., Mont, M. A., Bozic, K. J. et al: American academy of orthopaedic surgeons clinical practice guideline on: Preventing venous thromboembolic disease in patients undergoing elective hip and knee arthroplasty. J Bone Joint Surg Am 2012, 94:746.
  184. Rasmussen, M. S., Jørgensen, L. N. and Wille-Jørgensen, P.: Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery. Cochrane Database Syst Rev 2009:Cd004318.
  185. Forster, R. and Stewart, M.: Anticoagulants (extended duration) for prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair. Cochrane Database Syst Rev 2016, 3:Cd004179.
  186. Kauf, T. L., Svatek, R. S., Amiel, G. 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. J Urol 2014, 191:1721.
  187. Lee, C. T., Chang, S. S., Kamat, A. M. et al: Alvimopan accelerates gastrointestinal recovery after radical cystectomy: A multicenter randomized placebo-controlled trial. Eur Urol 2014, 66:265.
  188. Vaughan-Shaw, P. G., Fecher, I. C., Harris, S. and Knight, J. S.: 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. Dis Colon Rectum 2012, 55:611.
  189. Chaudhri, S., Brown, L., Hassan, I. and Horgan, A. F.: Preoperative intensive, community-based vs. Traditional stoma education: A randomized, controlled trial. Dis Colon Rectum 2005, 48:504.
  190. Colwell, J. C. and Gray, M.: Does preoperative teaching and stoma site marking affect surgical outcomes in patients undergoing ostomy surgery? J Wound Ostomy Continence Nurs 2007, 34:492.
  191. Leissner, J., Ghoneim, M. A., Abol-Enein, H. et al: Extended radical lymphadenectomy in patients with urothelial bladder cancer: Results of a prospective multicenter study. J Urol 2004, 171:139.
  192. Vazina, A., Dugi, D., Shariat, S. F. et al: Stage specific lymph node metastasis mapping in radical cystectomy specimens. J Urol 2004, 171:1830.
  193. Abdollah, F., Sun, M., Schmitges, J. et al: Stage-specific impact of pelvic lymph node dissection on survival in patients with non-metastatic bladder cancer treated with radical cystectomy. BJU Int 2012, 109:1147.
  194. Herr, H. W., Bochner, B. H., Dalbagni, G. et al: Impact of the number of lymph nodes retrieved on outcome in patients with muscle invasive bladder cancer. J Urol 2002, 167:1295.
  195. Konety, B. R., Joslyn, S. A. and O'Donnell, M. A.: 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. J Urol 2003, 169:946.
  196. Shirotake, S., Kikuchi, E., Matsumoto, K. et al: Role of pelvic lymph node dissection in lymph node-negative patients with invasive bladder cancer. Jpn J Clin Oncol 2010, 40:247.
  197. Fahmy, N., Aprikian, A., Tanguay, S. et al: Practice patterns and recurrence after partial cystectomy for bladder cancer. World J Urol 2010, 28:419.
  198. Capitanio, U., Isbarn, H., Shariat, S. F. et al: Partial cystectomy does not undermine cancer control in appropriately selected patients with urothelial carcinoma of the bladder: A population-based matched analysist. Urology 2009, 74:858.
  199. Amin, M. B., Greene, F. L., Edge, S. B. et al: The eighth edition ajcc cancer staging manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging. CA Cancer J Clin 2017, 67:93.
  200. Bochner, B. H., Cho, D., Herr, H. W. et al: Prospectively packaged lymph node dissections with radical cystectomy: Evaluation of node count variability and node mapping. J Urol 2004, 172:1286.
  201. Herr, H. W., Faulkner, J. R., Grossman, H. B. et al: Surgical factors influence bladder cancer outcomes: A cooperative group report. J Clin Oncol 2004, 22:2781.
  202. Brössner, C., Pycha, A., Toth, A. et al: Does extended lymphadenectomy increase the morbidity of radical cystectomy? BJU Int 2004, 93:64.
  203. Brunocilla, E., Pernetti, R., Schiavina, R. 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. Int Urol Nephrol 2013, 45:711.
  204. Dhar, N. B., Klein, E. A., Reuther, A. M. et al: Outcome after radical cystectomy with limited or extended pelvic lymph node dissection. J Urol 2008, 179:873.
  205. Leissner, J., Hohenfellner, R., Thüroff, J. W. and Wolf, H. K.: Lymphadenectomy in patients with transitional cell carcinoma of the urinary bladder; significance for staging and prognosis. BJU Int 2000, 85:817.
  206. Poulsen, A. L., Horn, T. and Steven, K.: Radical cystectomy: Extending the limits of pelvic lymph node dissection improves survival for patients with bladder cancer confined to the bladder wall. J Urol 1998, 160:2015.
  207. Zehnder, P., Studer, U. E., Skinner, E. C. et al: Super extended versus extended pelvic lymph node dissection in patients undergoing radical cystectomy for bladder cancer: A comparative study. J Urol 2011, 186:1261.
  208. Simone, G., Papalia, R., Ferriero, M. et al: Stage-specific impact of extended versus standard pelvic lymph node dissection in radical cystectomy. Int J Urol 2013, 20:390.
  209. Morgan, T. M., Barocas, D. A., Penson, D. F. et al: Lymph node yield at radical cystectomy predicts mortality in node-negative and not node-positive patients. Urology 2012, 80:632.
  210. Siemens, D. R., Mackillop, W. J., Peng, Y. et al: Lymph node counts are valid indicators of the quality of surgical care in bladder cancer: A population-based study. Urol Oncol 2015, 33:425.e15.
  211. Koppie, T. M., Vickers, A. J., Vora, K. et al: Standardization of pelvic lymphadenectomy performed at radical cystectomy: Can we establish a minimum number of lymph nodes that should be removed? Cancer 2006, 107:2368.
  212. Stein, J. P., Cai, J., Groshen, S. and Skinner, D. G.: Risk factors for patients with pelvic lymph node metastases following radical cystectomy with en bloc pelvic lymphadenectomy: Concept of lymph node density. J Urol 2003, 170:35.
  213. Wright, J. L., Lin, D. W. and Porter, M. P.: The association between extent of lymphadenectomy and survival among patients with lymph node metastases undergoing radical cystectomy. Cancer 2008, 112:2401.
  214. Froehner, M., Novotny, V., Heberling, U. et al: Relationship of the number of removed lymph nodes to bladder cancer and competing mortality after radical cystectomy. Eur Urol 2014, 66:987.
  215. Kaczmarek, K., Małkiewicz, B. and Lemiński, A.: Adequate pelvic lymph node dissection in radical cystectomy in the era of neoadjuvant chemotherapy: A meta-analysis and systematic review. Cancers (Basel) 2023, 15
  216. Tochigi, K., Nagayama, J., Bando, S. et al: Relationship between the number of lymph nodes dissected and prognosis in muscle-invasive bladder cancer in the era of neoadjuvant chemotherapy. Int J Urol 2022, 29:1264.
  217. Lemiński, A., Kaczmarek, K., Michalski, W. et al: The influence of lymph node count on oncological outcome of radical cystectomy in chemotherapy pre-treated and chemotherapy-naïve patients with muscle invasive bladder cancer. J Clin Med 2021, 10
  218. Kosiba, M., Stolzenbach, L. F., Collà Ruvolo, C. et al: Contemporary trends and efficacy of pelvic lymph node dissection at radical cystectomy for urothelial and variant histology carcinoma of the urinary bladder. Clin Genitourin Cancer 2022, 20:195.e1.
  219. Lerner, S. P., Tangen, C., Svatek, R. S. et al: Swog s1011: A phase iii surgical trial to evaluate the benefit of a standard versus an extended lymphadenectomy performed at time of radical cystectomy for muscle invasive urothelial cancer. Journal of Clinical Oncology 2023, 41:4508.
  220. Gschwend, J. E., Heck, M. M., Lehmann, J. et al: Extended versus limited lymph node dissection in bladder cancer patients undergoing radical cystectomy: Survival results from a prospective, randomized trial. Eur Urol 2019, 75:604.
  221. Kaufman, D. S., Winter, K. A., Shipley, W. U. 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. Oncologist 2000, 5:471.
  222. Hagan, M. P., Winter, K. A., Kaufman, D. S. 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. Int J Radiat Oncol Biol Phys 2003, 57:665.
  223. Kaufman, D. S., Winter, K. A., Shipley, W. U. 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. Urology 2009, 73:833.
  224. Herr, H. W.: Outcome of patients who refuse cystectomy after receiving neoadjuvant chemotherapy for muscle-invasive bladder cancer. Eur Urol 2008, 54:126.
  225. Herr, H. W., Bajorin, D. F. and Scher, H. I.: Neoadjuvant chemotherapy and bladder-sparing surgery for invasive bladder cancer: Ten-year outcome. J Clin Oncol 1998, 16:1298.
  226. Holzbeierlein, J. M., Lopez-Corona, E., Bochner, B. H. et al: Partial cystectomy: A contemporary review of the memorial sloan-kettering cancer center experience and recommendations for patient selection. J Urol 2004, 172:878.
  227. Kassouf, W., Swanson, D., Kamat, A. M. et al: Partial cystectomy for muscle invasive urothelial carcinoma of the bladder: A contemporary review of the m. D. Anderson cancer center experience. J Urol 2006, 175:2058.
  228. Herr, H. W.: Transurethral resection of muscle-invasive bladder cancer: 10-year outcome. J Clin Oncol 2001, 19:89.
  229. Duncan, W. and Quilty, P. M.: The results of a series of 963 patients with transitional cell carcinoma of the urinary bladder primarily treated by radical megavoltage x-ray therapy. Radiother Oncol 1986, 7:299.
  230. Blandy, J. P., Jenkins, B. J., Fowler, C. G. et al: Radical radiotherapy and salvage cystectomy for t2/3 cancer of the bladder. Prog Clin Biol Res 1988, 260:447.
  231. Jenkins, B. J., Caulfield, M. J., Fowler, C. G. et al: Reappraisal of the role of radical radiotherapy and salvage cystectomy in the treatment of invasive (t2/t3) bladder cancer. Br J Urol 1988, 62:343.
  232. Gospodarowicz, M. K., Rider, W. D., Keen, C. W. et al: Bladder cancer: Long-term follow-up results of patients treated with radical radiation. Clin Oncol (R Coll Radiol) 1991, 3:155.
  233. Jahnson, S., Pedersen, J. and Westman, G.: Bladder carcinoma--a 20-year review of radical irradiation therapy. Radiother Oncol 1991, 22:111.
  234. Fosså, S. D., Waehre, H., Aass, N. et al: Bladder cancer definitive radiation therapy of muscle-invasive bladder cancer. A retrospective analysis of 317 patients. Cancer 1993, 72:3036.
  235. Rozan, R., Albuisson, E., Donnarieix, D. et al: Interstitial iridium-192 for bladder cancer (a multicentric survey: 205 patients). Int J Radiat Oncol Biol Phys 1992, 24:469.
  236. Pernot, M., Hubert, J., Guillemin, F. et al: Combined surgery and brachytherapy in the treatment of some cancers of the bladder (partial cystectomy and interstitial iridium-192). Radiother Oncol 1996, 38:115.
  237. Pos, F., Horenblas, S., Dom, P. et al: Organ preservation in invasive bladder cancer: Brachytherapy, an alternative to cystectomy and combined modality treatment? Int J Radiat Oncol Biol Phys 2005, 61:678.
  238. Stein, J. P., Lieskovsky, G., Cote, R. et al: Radical cystectomy in the treatment of invasive bladder cancer: Long-term results in 1,054 patients. J Clin Oncol 2001, 19:666.
  239. van Hoogstraten, L. M. C., van Gennep, E. J., Kiemeney, L. et al: Occult lymph node metastases in patients without residual muscle-invasive bladder cancer at radical cystectomy with or without neoadjuvant chemotherapy: A nationwide study of 5417 patients. World J Urol 2022, 40:111.
  240. Efstathiou, J. A., Spiegel, D. Y., Shipley, W. U. et al: Long-term outcomes of selective bladder preservation by combined-modality therapy for invasive bladder cancer: The mgh experience. Eur Urol 2012, 61:705.
  241. Zlotta, A. R., Ballas, L. K., Niemierko, A. et al: Radical cystectomy versus trimodality therapy for muscle-invasive bladder cancer: A multi-institutional propensity score matched and weighted analysis. Lancet Oncol 2023, 24:669.
  242. James, N. D., Hussain, S. A., Hall, E. et al: Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med 2012, 366:1477.
  243. Coppin, C. M., Gospodarowicz, M. K., James, K. 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. J Clin Oncol 1996, 14:2901.
  244. Mitin, T., Hunt, D., Shipley, W. U. 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. Lancet Oncol 2013, 14:863.
  245. Caffo, O., Thompson, C., De Santis, M. 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. Radiother Oncol 2016, 121:193.
  246. De Santis, M., Bachner, M., Cerveny, M. et al: Combined chemoradiotherapy with gemcitabine in patients with locally advanced inoperable transitional cell carcinoma of the urinary bladder and/or in patients ineligible for surgery: A phase i trial. Ann Oncol 2014, 25:1789.
  247. Choudhury, A., Swindell, R., Logue, J. P. et al: Phase ii study of conformal hypofractionated radiotherapy with concurrent gemcitabine in muscle-invasive bladder cancer. J Clin Oncol 2011, 29:733.
  248. Coen, J. J., Zhang, P., Saylor, P. J. 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. J Clin Oncol 2019, 37:44.
  249. Ghate, K., Brennan, K., Karim, S. et al: Concurrent chemoradiotherapy for bladder cancer: Practice patterns and outcomes in the general population. Radiother Oncol 2018, 127:136.
  250. Rose, T. L., Deal, A. M., Ladoire, S. et al: Patterns of bladder preservation therapy utilization for muscle-invasive bladder cancer. Bladder Cancer 2016, 2:405.
  251. Rödel, C., Grabenbauer, G. G., Kühn, R. et al: Combined-modality treatment and selective organ preservation in invasive bladder cancer: Long-term results. J Clin Oncol 2002, 20:3061.
  252. Zietman, A. L., Grocela, J., Zehr, E. et al: Selective bladder conservation using transurethral resection, chemotherapy, and radiation: Management and consequences of ta, t1, and tis recurrence within the retained bladder. Urology 2001, 58:380.
  253. Picozzi, S., Ricci, C., Gaeta, M. et al: Upper urinary tract recurrence following radical cystectomy for bladder cancer: A meta-analysis on 13,185 patients. J Urol 2012, 188:2046.
  254. Sanderson, K. M., Cai, J., Miranda, G. 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. J Urol 2007, 177:2088.
  255. Tran, W., Serio, A. M., Raj, G. V. et al: Longitudinal risk of upper tract recurrence following radical cystectomy for urothelial cancer and the potential implications for long-term surveillance. J Urol 2008, 179:96.
  256. Hall, M. C., Koch, M. O. and McDougal, W. S.: Metabolic consequences of urinary diversion through intestinal segments. Urol Clin North Am 1991, 18:725.
  257. Harraz, A. M., Mosbah, A., El-Assmy, A. et al: Renal function evaluation in patients undergoing orthotopic bladder substitution: A systematic review of literature. BJU Int 2014, 114:484.
  258. Amini, E. and Djaladat, H.: Long-term complications of urinary diversion. Curr Opin Urol 2015, 25:570.
  259. Krajewski, W., Piszczek, R., Krajewska, M. et al: Urinary diversion metabolic complications - underestimated problem. Adv Clin Exp Med 2014, 23:633.
  260. Tan, W. S., Lamb, B. W. and Kelly, J. D.: Complications of radical cystectomy and orthotopic reconstruction. Adv Urol 2015, 2015:323157.
  261. Van der Aa, F., Joniau, S., Van Den Branden, M. and Van Poppel, H.: Metabolic changes after urinary diversion. Adv Urol 2011, 2011:764325.
  262. Volkmer, B. G., Schnoeller, T., Kuefer, R. et al: Upper urinary tract recurrence after radical cystectomy for bladder cancer--who is at risk? J Urol 2009, 182:2632.
  263. Raj, G. V., Bochner, B. H., Serio, A. M. et al: Natural history of positive urinary cytology after radical cystectomy. J Urol 2006, 176:2000.
  264. Sullivan, P. S., Nooraie, F., Sanchez, H. et al: Comparison of immunocyt, urovysion, and urine cytology in detection of recurrent urothelial carcinoma: A "split-sample" study. Cancer 2009, 117:167.
  265. Dimashkieh, H., Wolff, D. J., Smith, T. M. et al: Evaluation of urovysion and cytology for bladder cancer detection: A study of 1835 paired urine samples with clinical and histologic correlation. Cancer Cytopathol 2013, 121:591.
  266. Chang, S. S., Boorjian, S. A., Chou, R. et al: Diagnosis and treatment of non-muscle invasive bladder cancer: Aua/suo guideline. J Urol 2016, 196:1021.
  267. Sherwood, J. B. and Sagalowsky, A. I.: The diagnosis and treatment of urethral recurrence after radical cystectomy. Urol Oncol 2006, 24:356.
  268. Clark, P. E. and Hall, M. C.: Contemporary management of the urethra in patients after radical cystectomy for bladder cancer. Urol Clin North Am 2005, 32:199.
  269. Tobisu, K., Tanaka, Y., Mizutani, T. and Kakizoe, T.: Transitional cell carcinoma of the urethra in men following cystectomy for bladder cancer: Multivariate analysis for risk factors. J Urol 1991, 146:1551.
  270. Nieder, A. M., Sved, P. D., Gomez, P. et al: Urethral recurrence after cystoprostatectomy: Implications for urinary diversion and monitoring. Urology 2004, 64:950.
  271. Knapik, J. A. and Murphy, W. M.: Urethral wash cytopathology for monitoring patients after cystoprostatectomy with urinary diversion. Cancer 2003, 99:352.
  272. Lin, D. W., Herr, H. W. and Dalbagni, G.: Value of urethral wash cytology in the retained male urethra after radical cystoprostatectomy. J Urol 2003, 169:961.
  273. Boorjian, S. A., Kim, S. P., Weight, C. J. et al: Risk factors and outcomes of urethral recurrence following radical cystectomy. Eur Urol 2011, 60:1266.
  274. Bassett, J. C., Gore, J. L., Chi, A. C. et al: Impact of a bladder cancer diagnosis on smoking behavior. J Clin Oncol 2012, 30:1871.
  275. Karam-Hage, M., Cinciripini, P. M. and Gritz, E. R.: Tobacco use and cessation for cancer survivors: An overview for clinicians. CA Cancer J Clin 2014, 64:272.
  276. Supportive, P. D. Q. and Palliative Care Editorial, B.: Smoking in cancer care (pdq®): Health professional version. In: Pdq cancer information summaries. Bethesda (MD): National Cancer Institute (US), 2002
  277. Supportive, P. D. Q. and Palliative Care Editorial, B.: Nutrition in cancer care (pdq®): Health professional version. In: Pdq cancer information summaries. Bethesda (MD): National Cancer Institute (US), 2002
  278. Siefker-Radtke, A. O., Kamat, A. M., Grossman, H. B. et al: Phase ii clinical trial of neoadjuvant alternating doublet chemotherapy with ifosfamide/doxorubicin and etoposide/cisplatin in small-cell urothelial cancer. J Clin Oncol 2009, 27:2592.
  279. Patel, S. G., Stimson, C. J., Zaid, H. B. et al: Locoregional small cell carcinoma of the bladder: Clinical characteristics and treatment patterns. J Urol 2014, 191:329.
  280. Choong, N. W., Quevedo, J. F. and Kaur, J. S.: Small cell carcinoma of the urinary bladder. The mayo clinic experience. Cancer 2005, 103:1172.
  281. Quek, M. L., Nichols, P. W., Yamzon, J. et al: Radical cystectomy for primary neuroendocrine tumors of the bladder: The university of southern california experience. J Urol 2005, 174:93.
  282. Kaushik, D., Frank, I., Boorjian, S. A. et al: Long-term results of radical cystectomy and role of adjuvant chemotherapy for small cell carcinoma of the bladder. Int J Urol 2015, 22:549.
  283. Siefker-Radtke, A. O., Dinney, C. P., Abrahams, N. A. et al: Evidence supporting preoperative chemotherapy for small cell carcinoma of the bladder: A retrospective review of the m. D. Anderson cancer experience. J Urol 2004, 172:481.
  284. Eswara, J. R., Heney, N. M., Wu, C. L. and McDougal, W. S.: Long-term outcomes of organ preservation in patients with small cell carcinoma of the bladder. Urol Int 2015, 94:401.
  285. Mattes, M. D., Kan, C. C., Dalbagni, G. et al: External beam radiation therapy for small cell carcinoma of the urinary bladder. Pract Radiat Oncol 2015, 5:e17.
  286. Meijer, R. P., Meinhardt, W., van der Poel, H. G. et al: Local control rate and prognosis after sequential chemoradiation for small cell carcinoma of the bladder. Int J Urol 2013, 20:778.
  287. Bryant, C. M., Dang, L. H., Stechmiller, B. K. et al: Treatment of small cell carcinoma of the bladder with chemotherapy and radiation after transurethral resection of a bladder tumor. Am J Clin Oncol 2016, 39:69.
  288. Meeks, J. J., Taylor, J. M., Matsushita, K. et al: Pathological response to neoadjuvant chemotherapy for muscle-invasive micropapillary bladder cancer. BJU Int 2013, 111:E325.
  289. Kamat, A. M., Dinney, C. P., Gee, J. R. et al: Micropapillary bladder cancer: A review of the university of texas m. D. Anderson cancer center experience with 100 consecutive patients. Cancer 2007, 110:62.
  290. Ghoneim, I. A., Miocinovic, R., Stephenson, A. J. et al: Neoadjuvant systemic therapy or early cystectomy? Single-center analysis of outcomes after therapy for patients with clinically localized micropapillary urothelial carcinoma of the bladder. Urology 2011, 77:867.
  291. de Ruiter, B. M., van Hattum, J. W., Lipman, D. et al: Phase 1 study of chemoradiotherapy combined with nivolumab ± ipilimumab for the curative treatment of muscle-invasive bladder cancer. Eur Urol 2022, 82:518.
  292. Maibom, S. L., Røder, M. A., Aasvang, E. K. et al: Open vs robot-assisted radical cystectomy (borarc): A double-blinded, randomised feasibility study. BJU Int 2022, 130:102.
  293. Vejlgaard, M., Maibom, S. L., Joensen, U. N. et al: Quality of life and secondary outcomes for open versus robot-assisted radical cystectomy: A double-blinded, randomised feasibility trial. World J Urol 2022, 40:1669.