Surgery With or Without Postoperative Intensity Modulated Radiation Therapy in Treating Patients With Urothelial Bladder Cancer
Condition: Stage III Bladder Cancer; Stage IV Bladder Cancer
MeSH terms: Urinary Bladder Neoplasms
Intervention: Intensity-Modulated Radiation Therapy
Intervention description: 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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