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

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.

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