Adjuvant Radiation for High Risk Bladder Cancer

Study Overview
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Brief Summary
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This phase II trial studies how well modern, conformal radiation therapy after surgery works in treating patients with high-risk bladder cancer. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue.

Detailed Description
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PRIMARY OBJECTIVE: I. Determine the feasibility of adjuvant radiation in the management of high-risk disease. SECONDARY OBJECTIVES: I. Prospectively evaluate patterns of failure in high-risk bladder cancer patients after cystectomy and aggressive adjuvant therapy. II. Define surgical and histopathologic parameters predictive of local and distant outcomes (e.g. grade, lymphovascular space invasion [LVSI], extent of resection/lymph node dissection [LND]). III. Assess quality of life (QoL) outcomes after this treatment using a standardized questionnaires (Functional Assessment of Cancer Therapy-General [FACT-G], FACT-Bladder Cancer [BL], Expanded Prostate Cancer Index Composite [EPIC] Bowel and Urinary). OUTLINE: Within 24 weeks of surgical resection, patients undergo 3D conformal radiation therapy once daily 5 days per week for 28 fractions. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 4 weeks, every 3 months for 2 years, every 6 months for 3-5 years, and then annually thereafter.

Official Title
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Phase II Study of Adjuvant 3D-Conformal Radiotherapy in High Risk Bladder Cancer

Conditions
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Bladder Cancer, Squamous Cell Carcinoma of the Bladder, Stage III Bladder Cancer, Stage IV Bladder Cancer, Transitional Cell Carcinoma of the Bladder

Intervention / Treatment
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* Radiation: 3D conformal radiation therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologic diagnosis of urothelial or squamous cell carcinoma of the bladder Patients must have undergone cystectomy (total cystectomy, radical cystectomy +/- pelvic lymph node dissection) with no evidence of macroscopic residual disease Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status of 0-2 Patients treated with simple cystectomy with macroscopically negative margins are eligible for this study Clinical T-stage (prior to systemic therapy, if applicable) ≥ T3a and/or positive lymph nodes by transurethral resection of bladder tumor (TURBT)/magnetic resonance imaging (MRI)/computed tomography (CT)/positron emission tomography (PET)-CT or pathologic T-stage ≥ T3a and/or positive lymph nodes Exclusion Criteria: Patients with metastatic disease outside of the pelvis Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years Prior radiation therapy to the pelvis Patients with active inflammatory bowel disease Severe acute co-morbidity, defined as follows: Unstable angina and/or congestive heart failure requiring hospitalization in the last 3 months Transmural myocardial infarction within the last 6 months Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is necessary because the treatment involved in this protocol may be significantly immunosuppressive; protocol-specific requirements may also exclude immunocompromised patients

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3D conformal radiation therapy<br>Within 24 weeks of surgical resection, patients undergo conformal radiation therapy once daily 5 days per week for 28 fractions. Treatment continues in the absence of disease progression or unacceptable toxicity. | Radiation: 3D conformal radiation therapy<br>* Undergo conformal radiation therapy<br>* Other names: Intensity Modulated Radiotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastrointestinal (GI) late effects, assessed using Radiation Therapy Oncology Group (RTOG) Late Effects in Normal Tissues (LENT)/Subjective, Objective, Management and Analytic (SOMA) scales | For purposes of this study, bowel adverse events are defined as the following: diarrhea, enteritis, fistula, ileus, incontinence, obstruction, perforation, proctitis, and stricture/stenosis (including anastomotic) as graded buy Common Terminology for Adverse Events (CTCAE) version 4.0. | 3 months to 10 yrs | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute adverse events greater than grade 2, graded by CTCAE version 4.0 |  | Up to 90 days | 
| Loco-regional failure, considered any failure in the treatment field of the pelvis | The cumulative incidence approach will be used to estimate the failure rate for local-regional and distant failures. | Up to 5 years | 
| Rate of distant metastases | Nodal disease beyond the common iliac will be considered distant failure. The cumulative incidence approach will be used to estimate the failure rate for distant failure. | Up to 5 years | 
| Rate of disease-free survival | Any tumor recurrence, development of distant metastases or death is considered a failure. The Kaplan-Meier method will be used to estimate the disease-free survival rate. | Up to 5 years | 
| Overall survival rate | Death from any cause is considered a failure. The Kaplan-Meier method will be used to estimate the overall survival. | Up to 5 years | 
| Quality of life, assessed using FACT-BL |  | Up to 5 years |