Surgery With or Without Postoperative Intensity Modulated Radiation Therapy in Treating Patients With Urothelial Bladder Cancer

Randomized Phase II Trial of Postoperative Adjuvant IMRT Following Cystectomy for pT3/T4 Urothelial Bladder Cancer

This randomized phase II trial studies the side effects and how well postoperative intensity modulated radiotherapy works after surgery in treating patients with urothelial bladder cancer. Radiation therapy uses high energy x-rays to kill tumor cells left behind in the pelvis after surgery. It is not yet known whether surgery followed by radiotherapy is more effective than surgery alone in treating patients with urothelial bladder cancer.

Study Overview

• Status: Terminated
• Conditions: Stage III Bladder Cancer; Stage IV Bladder Cancer
• Intervention / Treatment: Radiation: Intensity-Modulated Radiation Therapy

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the ability of postcystectomy adjuvant radiotherapy to safely reduce pelvic tumor recurrence, defined as pelvic recurrence-free survival.

SECONDARY OBJECTIVES:

I. Evaluate increase in disease-free survival. II. Evaluate toxicity of adjuvant pelvic radiotherapy.

OUTLINE: Patients are randomized to 1 of 2 treatment arms. Patients are stratified by neoadjuvant preoperative or postoperative adjuvant chemotherapy.

After completion of study treatment, patients are followed up at 6 weeks, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually for 5 years.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 5G2
      • Arthur J E Child Comprehensive Cancer Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre at Hamilton Health Sciences
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital and Cancer Center-General Campus
    • Toronto, Ontario, Canada, M4N 3M5
      • Odette Cancer Centre- Sunnybrook Health Sciences Centre
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
    • Montreal, Quebec, Canada, H2W 1S6
      • McGill University Department of Oncology
    • Montreal, Quebec, Canada, H2X 3E4
      • CHUM - Centre Hospitalier de l'Universite de Montreal
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre
• Israel
  • Petah Tikva, Israel, 49100
    • Rabin Medical Center
• United States
  • California
    • Bakersfield, California, United States, 93301
      • AIS Cancer Center at San Joaquin Community Hospital
    • Greenbrae, California, United States, 94904
      • Marin General Hospital
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90033
      • Los Angeles General Medical Center
    • Palo Alto, California, United States, 94304
      • Stanford Cancer Institute Palo Alto
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • UCHealth University of Colorado Hospital
    • Colorado Springs, Colorado, United States, 80907
      • Penrose-Saint Francis Healthcare
    • Colorado Springs, Colorado, United States, 80909
      • UCHealth Memorial Hospital Central
    • Fort Collins, Colorado, United States, 80524
      • Poudre Valley Hospital
  • Delaware
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
    • Rehoboth Beach, Delaware, United States, 19971
      • Beebe Health Campus
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University Hospital Midtown
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital/Winship Cancer Institute
    • Atlanta, Georgia, United States, 30342
      • Emory Saint Joseph's Hospital
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Medical Center-Gainesville
    • Savannah, Georgia, United States, 31405
      • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
  • Idaho
    • Boise, Idaho, United States, 83712
      • Saint Luke's Cancer Institute - Boise
    • Fruitland, Idaho, United States, 83619
      • Saint Luke's Cancer Institute - Fruitland
    • Meridian, Idaho, United States, 83642
      • Saint Luke's Cancer Institute - Meridian
    • Nampa, Idaho, United States, 83687
      • Saint Luke's Cancer Institute - Nampa
    • Twin Falls, Idaho, United States, 83301
      • Saint Luke's Cancer Institute - Twin Falls
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Pekin, Illinois, United States, 61554
      • OSF Saint Francis Radiation Oncology at Pekin
    • Peoria, Illinois, United States, 61637
      • OSF Saint Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • OSF Saint Francis Radiation Oncology at Peoria Cancer Center
    • Springfield, Illinois, United States, 62781
      • Springfield Memorial Hospital
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
  • Indiana
    • Fort Wayne, Indiana, United States, 46805
      • Parkview Hospital Randallia
    • Fort Wayne, Indiana, United States, 46804
      • Radiation Oncology Associates PC
    • Goshen, Indiana, United States, 46526
      • Goshen Center for Cancer Care
    • Mishawaka, Indiana, United States, 46545
      • Memorial Regional Cancer Center Day Road
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic - Ames
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Wichita, Kansas, United States, 67214
      • Ascension Via Christi Hospitals Wichita
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Hospital Pavilion and Medical Campus
    • Louisville, Kentucky, United States, 40245
      • UofL Health Medical Center Northeast
  • Maine
    • Scarborough, Maine, United States, 04074
      • MaineHealth Maine Medical Center- Scarborough
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland/Greenebaum Cancer Center
    • Bel Air, Maryland, United States, 21014
      • UM Upper Chesapeake Medical Center
    • Columbia, Maryland, United States, 21044
      • Central Maryland Radiation Oncology in Howard County
    • Glen Burnie, Maryland, United States, 21061
      • UM Baltimore Washington Medical Center/Tate Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital and Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • Trinity Health Saint Joseph Mercy Hospital Ann Arbor
    • Brownstown, Michigan, United States, 48183
      • Henry Ford Cancer Institute-Downriver
    • Clarkston, Michigan, United States, 48346
      • Michigan Healthcare Professionals Clarkston
    • Clinton Township, Michigan, United States, 48038
      • Henry Ford Macomb Hospital-Clinton Township
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Farmington Hills, Michigan, United States, 48334
      • Michigan Healthcare Professionals Farmington
    • Livonia, Michigan, United States, 48154
      • Trinity Health Saint Mary Mercy Livonia Hospital
    • Pontiac, Michigan, United States, 48341
      • Trinity Health Saint Joseph Mercy Oakland Hospital
    • Royal Oak, Michigan, United States, 48073
      • Corewell Health William Beaumont University Hospital
    • Troy, Michigan, United States, 48098
      • Michigan Healthcare Professionals Troy
    • Troy, Michigan, United States, 48085
      • Corewell Health Beaumont Troy Hospital
  • Minnesota
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • City of Saint Peters, Missouri, United States, 63376
      • Siteman Cancer Center at Saint Peters Hospital
    • Creve Coeur, Missouri, United States, 63141
      • Siteman Cancer Center at West County Hospital
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • St Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic Cancer Center
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
  • Nevada
    • Reno, Nevada, United States, 89502
      • Renown Regional Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
  • New Jersey
    • Mount Holly, New Jersey, United States, 08060
      • Virtua Memorial
    • Somerville, New Jersey, United States, 08876
      • Robert Wood Johnson University Hospital Somerset
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • New Mexico Oncology Hematology Consultants
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Cancer Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
    • White Plains, New York, United States, 10601
      • Dickstein Cancer Treatment Center
  • Ohio
    • Sylvania, Ohio, United States, 43560
      • ProMedica Flower Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Oregon
    • Coos Bay, Oregon, United States, 97420
      • Bay Area Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania/Abramson Cancer Center
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital
  • South Carolina
    • Boiling Springs, South Carolina, United States, 29316
      • Prisma Health Cancer Institute - Spartanburg
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Cancer Institute - Faris
    • Greenville, South Carolina, United States, 29607
      • Saint Francis Cancer Center
    • Greenville, South Carolina, United States, 29615
      • Prisma Health Cancer Institute - Eastside
    • Greer, South Carolina, United States, 29650
      • Prisma Health Cancer Institute - Greer
    • Seneca, South Carolina, United States, 29672
      • Prisma Health Cancer Institute - Seneca
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University/Ingram Cancer Center
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern/Simmons Cancer Center-Dallas
    • Galveston, Texas, United States, 77555-0565
      • University of Texas Medical Branch
    • League City, Texas, United States, 77573
      • UTMB Cancer Center at Victory Lakes
  • Utah
    • Logan, Utah, United States, 84321
      • Logan Regional Hospital
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center
    • Ogden, Utah, United States, 84403
      • McKay-Dee Hospital Center
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists-Salt Lake City
  • Vermont
    • Saint Johnsbury, Vermont, United States, 05819
      • Dartmouth Cancer Center - North
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center - Montlake
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Center
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Healthcare
  • Wisconsin
    • Grafton, Wisconsin, United States, 53024
      • Aurora Cancer Care-Grafton
    • Green Bay, Wisconsin, United States, 54311
      • Aurora BayCare Medical Center
    • Kenosha, Wisconsin, United States, 53142
      • Aurora Cancer Care-Kenosha South
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center - University Hospital
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Saint Luke's Medical Center
    • Milwaukee, Wisconsin, United States, 53233
      • Aurora Sinai Medical Center
    • Oshkosh, Wisconsin, United States, 54904
      • Vince Lombardi Cancer Clinic - Oshkosh
    • Sheboygan, Wisconsin, United States, 53081
      • Vince Lombardi Cancer Clinic-Sheboygan
    • Summit, Wisconsin, United States, 53066
      • Aurora Medical Center in Summit
    • Two Rivers, Wisconsin, United States, 54241
      • Vince Lombardi Cancer Clinic-Two Rivers
    • West Allis, Wisconsin, United States, 53227
      • Aurora West Allis Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria (A patient cannot be considered eligible for this study unless ALL of the following conditions are met.):

• Initial histological diagnosis of muscle invasive urothelial carcinoma

• Patients must have undergone a radical cystectomy (reconstructed urinary diversion may be non-continent diversions (eg, ileal conduits) or continent non-orthotopic catheterizable diversions (eg, Indiana pouch) or continent orthotopic diversions (eg, Studer pouch or neobladder)for urothelial bladder carcinoma within 105 days prior to registration. Final cystectomy pathology must be either pure urothelial carcinoma or dominant urothelial carcinoma with admixture of other histologies excluding small cell variants.

  • Neoadjuvant (preoperative) or adjuvant (postoperative) chemotherapy for the bladder cancer is permitted; however, all patients, even those who will receive adjuvant chemotherapy, must be registered within 105 days after completing cystectomy regardless of whether adjuvant chemotherapy has started. Patients who will be receiving adjuvant (postoperative) chemotherapy will be randomized within 28 days of completing that chemotherapy.

• Patients with the following pTNM stages per the American Joint Committee on Cancer (AJCC) 7th ed. are eligible:

  • pT3apN0; pN1; pN2 provided less than 10 nodes dissected and/or positive surgical margins
  • pT3bpN0; pN1; pN2
  • pT4apN0; pN1; pN2
  • pT4bpN0; pN1; pN2

• Appropriate stage for study entry based on the following diagnostic workup:

  • History/physical examination =< 45 days prior to registration;
  • CT or MRI or positron emission tomography(PET)-CT that includes chest, abdomen and pelvis should be performed for initial radiological staging. This may be performed pre- or post-surgery ≤ 90 days prior to registration except in patients getting postoperative adjuvant chemotherapy, who will require CT, MRI or PET-CT including the chest and abdomen and pelvis no more than 30 days prior to registration. Imaging performed postoperatively should show no evidence of residual disease.
• Age >=18
• Zubrod performance status 0-2 =< 45 days prior to registration

• Complete blood count (CBC)/differential obtained ≤ 14 days prior to registration with adequate bone marrow function defined as follows:

  • Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
  • Platelets >= 100,000 cells/mm^3
  • Hemoglobin >= 8.0 g/dl (NOTE: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable)
  • The patient must provide study-specific informed consent prior to study entry
• The patient must provide study-specific informed consent prior to study entry.

Exclusion Criteria (Patients with any of the following conditions are NOT eligible for this study.):

• Definitive clinical or radiologic evidence of metastatic disease; pN3 disease is not allowed (positive common iliac node).
• Prior invasive solid tumor or hematological malignancy (except non-melanomatous skin cancer and incidentally discovered prostate cancer at time of cystoprostatectomy) unless disease free for a minimum of 3 years
• Prior radiotherapy to the pelvis
• Patients with a history of inflammatory bowel disease
• Patients who have required any treatment (medical or surgical) for bowel obstruction prior to diagnosis of bladder cancer or who have required surgical treatment for bowel obstruction after the cystectomy

• Severe, active co-morbidity defined as follows:

  • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;
  • Transmural myocardial infarction within the last 6 months;
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;
  • Severe hepatic disease, defined as a diagnosis of Child-Pugh Class B or C hepatic disease;
  • HIV positive with CD4 count < 200 cells/microliter. Note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count ≥ 200 cells/microliter within 30 days prior to registration. Note also that HIV testing is not required for eligibility for this protocol.
  • Other major medical illness which requires hospitalization or precludes study therapy at the time of registration.
• Women who are breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: No Radiation Therapy; Patients do not receive radiation therapy (RT).
Experimental: Intensity-modulated radiation therapy (IMRT); Postoperative adjuvant intensity-modulated radiation therapy (IMRT).	Radiation: Intensity-Modulated Radiation Therapy; Postoperative adjuvant IMRT radiotherapy 50.4 Gy in 28 fractions. In patients not getting postoperative adjuvant chemotherapy the radiation treatment must begin within 140 days after cystectomy. For patients getting adjuvant chemotherapy radiation treatment must start within 49 days of completing chemotherapy.; Other Names: IMRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pelvic Recurrence-free Survival (PRFS)	PRFS is defined as time free of pelvic recurrence or death, with patients who experience distant metastasis censored at the time of occurrence. Pelvic recurrence is specifically defined as soft tissue and /or lymph node tumor recurrence in the pelvis anywhere between the L5-S1 disc space superiorly and the pelvic floor inferiorly. This was to be determined on the basis of pelvic imaging (CT or MRI scan demonstrating soft tissue or nodal recurrence at least 1cm in linear dimension) or urethroscopy; biopsy was not required. PRFS was to be tested between arms in terms of a difference in cause-specific-hazards using the log-rank test and cumulative incidence of PRFS in the presence of competing risks was to be computed via cumulative incidence. Due to early termination with few patients, only counts of events have been calculated.	From randomization to study termination, maximum follow-up was 13.3 months, median follow-up was 1.9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Free Survival (DFS)	Disease free survival (DFS) is defined as the first occurrence of either: pelvic failure, distant metastasis, or death and was to be estimated by the Kaplan-Meier method and arms compared using the log-rank test. Pelvic recurrence is specifically defined as soft tissue and /or lymph node tumor recurrence in the pelvis anywhere between the L5-S1 disc space superiorly and the pelvic floor inferiorly. This was to be determined on the basis of pelvic imaging (CT or MRI scan demonstrating soft tissue or nodal recurrence at least 1cm in linear dimension) or urethroscopy; biopsy was not required. Distant metastases is defined as any hematogenous metastases and/or lymph node metastases above the L5-S1 interspace, documented by imaging (CT and/or MRI and/or bone scans). Due to early termination with few patients, only counts of events have been calculated.	From randomization to study termination, maximum follow-up was 13.3 months, median follow-up was 1.9 months
Number of Patients With Bowel Toxicity	Adverse events (AE) evaluated using Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Bowel toxicity= abdominal distension/pain, colitis, colonic fistula/ hemorrhage/obstruction/perforation/stenosis/ulcer, diarrhea, enterocolitis, fecal incontinence/gastrointestinal/fistula/pain, ileal fistula/hemorrhage/obstruction/perforation/stenosis/ulcer, Ileus, jejunal fistula/hemorrhage/obstruction/perforation/stenosis/ulcer, lower gastrointestinal hemorrhage, rectal fistula/hemorrhage/mucositis/necrosis/obstruction/pain/perforation/stenosis/ulcer, small intestinal mucositis/obstruction/perforation/stenosis/ulcer, vomiting. Highest grade adverse event per subject counted. Grade refers to AE severity and ranges from 1 to 5 with unique clinical descriptions of severity for each AE based on this general guideline: 1 Mild, 2 Moderate, 3 Severe, 4 Life-threatening or disabling, 5 Death related to AE.	From randomization to study termination, maximum follow-up was 13.3 months, median follow-up was 1.9 months

Collaborators and Investigators

• Sponsor: NRG Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Libni Eapen, NRG Oncology

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2015
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: December 10, 2014
• First Submitted That Met QC Criteria: December 10, 2014
• First Posted (Estimated): December 15, 2014

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urologic Neoplasms; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Therapeutics; Radiotherapy; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy, Intensity-Modulated
• Other Study ID Numbers: NRG-GU001 (Other Identifier: CTEP); U10CA180868 (U.S. NIH Grant/Contract); NCI-2014-02061 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.