Adjuvant Proton Therapy or IMRT for the Treatment of Bladder Cancer
Adjuvant Proton Therapy or IMRT for the Treatment of Bladder Cancer
Invasive urothelial bladder cancer is a common malignancy causing 14,000 deaths annually in
 the United States. The primary objective of the feasibility/Phase I portion of the study is
 to establish the feasibility and safety of proton and the safety of IMRT for patients with
 pure or mixed variant urothelial carcinoma.
Invasive urothelial bladder cancer is a common malignancy causing 14,000 deaths annually in
 the United States. The primary objective of the feasibility/Phase I portion of the study is
 to establish the feasibility and safety of proton and the safety of IMRT. Safety will be
 based on acute toxicity. The primary objective of the phase II study is to generate estimates
 of the local failure rate for intermediate and high risk patients treated with either proton
 therapy or IMRT. The study, however, is not explicitly designed to compare outcomes of proton
 therapy and IMRT. Secondary objectives include further evaluation of acute and late toxicity,
 quality of life and estimation of overall survival.
Inclusion Criteria:

 -  Pure or mixed variant urothelial carcinoma o Allowable mixed variant subtypes include:
 squamous differentiation glandular differentiation nested pattern microcystic
 micropapillary lymphoepthelioma-like plasmacytoid and lymphoma-like
 sarcomatoid/carcinosarcoma giant cell trophoblastic differentiation clear cell lipid
 cell undifferentiated Radical cystectomy and pelvic lymph node dissection within the
 prior 48 weeks Pathologic T3 or higher stage disease, N0-2, M0 (AJCC, 7th Ed.,
 Appendix C) No clinical evidence of residual or recurrent disease based on the
 following minimum diagnostic work-up within 8 weeks of a patients consent to
 participate.

 -  History and physical examination

 -  Chest imaging by x-ray (PA and lateral views) or CT scan (with or without IV
 contrast);

 -  Axial abdominal and pelvic imaging by MRI (preferably with gadolinium)

 -  Bone scan

 -  Patients with microscopically involved (positive) surgical margins, but no
 grossly evident residual disease by imaging or physical exam are eligible.

 The patient is a candidate for definitive external beam radiotherapy;

 -  No prior radiotherapy to the region of study;

 -  No inflammatory bowel disease, active collagen vascular or connective tissue
 disorders, and no other medical or social contraindications to radiotherapy, as
 determined by a participating radiation oncologist; Age ³18 years ECOG performance
 status: 0-2 Concurrent noninvestigational medications will be permitted Informed
 consent: Patients must have the ability to understand and be willing to sign the
 study-specific informed consent indicating their understanding of the investigational
 nature and the risks of this study before any of the protocol related studies are
 preformed (this does not include routine laboratory testing or imaging studies
 required to establish study eligibility);

 Exclusion Criteria:

 -  Unstable renal function in the month prior to registration defined as a creatinine
 rise of 1 mg/dL Prior partial or complete small bowel obstruction either before or
 after radical cystectomy Prior radiotherapy to the pelvis; o Prior radiation therapy
 for a different cancer or disease process is allowed, provided there will be no
 overlap of radiation therapy fields between the participants prior and current course
 of radiation therapy, radiotherapy was completed more than four weeks from enrolling
 in this study.

 Planned concurrent chemotherapy or other investigational drug to be given with radiation
 treatments o Prior chemotherapy or investigational drug for bladder cancer or a different
 cancer is allowed, provided that: The therapy was completed more than two weeks prior to
 the start of adjuvant pelvic radiation The participant has recovered to Grade 1 toxicity
 from agents previously administered Subtotal surgical resection with clinically evident
 residual disease by physical exam or axial imaging.

 Prior or concurrent second invasive malignancy other than prostate and non-melanoma skin
 cancers, unless disease free for a minimum of five years. If a patient had a concurrent
 prostate cancer, then it must have been resected to negative margins.

 Known severe, active co-morbidity, defined as follows:

 o Any clinically significant unrelated systemic illness, medical condition, or other
 factor, which at the discretion of the Principal Investigators, would interfere in the safe
 and timely completion of study procedures, compromise the patients ability to tolerate the
 protocol therapy, or is likely to interfere with the study procedures or results.