Radical Cystectomy Compared With Chemoradiation for Muscle Invasive Bladder Cancer

Currently the standard treatment of muscle invasive bladder cancer is the complete removal of
bladder and adjacent organs, such as prostate or ovaries. Such procedure is highly invasive
and undesirable for some patients.

The researchers hope to learn if chemoradiation, using chemotherapy and radiation, can be a
good alternative therapy option. Chemoradiation therapy is also currently considered an
acceptable clinical approach but is typically used for treatment in patients with muscle
invasive bladder cancer who have other medical issues that might cause complications during
or after undergoing surgery. Disease free survival at 5 years is better for those who had
their bladder removed, but overall survival rates for chemoradiation therapy patients are
comparable between the two approaches.

Inclusion Criteria:

- Pathologically (histologically) proven diagnosis of primary carcinoma of the bladder
(transitional cell cancer) within 8 weeks of registration. Operable patients whose
tumors are primary carcinomas of the bladder and exhibit histologic evidence of
muscularis propria invasion and are AJCC clinical stages T2-T4a, Nx or N0, M0

- If radiologic evaluation of a lymph node is interpreted as "positive", this must be
evaluated further either by lymphadenectomy or percutaneous needle biopsy. Patients
with histologically or cytologically confirmed node metastases or any other metastases
will not be eligible.

- Patients must have an adequately functioning bladder after thorough evaluation by an
urologist and have undergone as thorough a transurethral resection of the bladder
tumor as is judged safely possible.

- Patients must be considered able to tolerate systemic chemotherapy combined with
pelvic radiation therapy, and a radical cystectomy by the joint agreement of the
participating Urologist, Radiation Oncologist, and Medical Oncologist.

- History and physical examination including weight, performance status, and body
surface area within 8 weeks prior to study registration

- Zubrod Performance Status 0-2

- Age ≥ 18;

- CBC/differential obtained no more than 4 weeks prior to registration on study, with
adequate bone marrow function defined as follows:

1. WBC ≥ 4000/ml

2. Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3;

3. Platelets ≥ 100,000 cells/mm3;

4. Hemoglobin ≥ 10.0 mg/dl (Note: The use of transfusion or other intervention to
achieve Hgb ≥ 10.0 g/dl is acceptable.);

- Serum creatinine of 1.5 mg% or less; serum bilirubin of 2.0 mg% or less; creatinine
clearance of 60 ml/min or greater no more than 4 weeks prior to registration; Note:
Calculated creatinine clearance is permissible. If the creatinine clearance is > 60
ml/min, then a serum creatinine of up to 1.8 mg% is allowable at the discretion of the
principle investigator;

- Serum pregnancy test for female patients of childbearing potential, ≤ 72 hours prior
to study entry; women of childbearing potential and male participants must practice
adequate contraception.

- Patient must be able to provide study-specific informed consent prior to study entry

Exclusion Criteria:

- Unable and unwilling to provide informed consent

- Evidence of distant metastases or histologically or cytologically proven lymph node
metastases

- Previous systemic chemotherapy (for any cancer) or pelvic radiation therapy

- A prior or concurrent malignancy of any other site or histology unless the patient has
been disease-free for ≥ 5 years except for non-melanoma skin cancer and/or stage T1a
prostate cancer or carcinoma in situ of the uterine cervix

- Patients judged not to be candidates for radical cystectomy; patients with pN+ or T4b
disease are considered to have unresectable disease

- Patients receiving any drugs that have potential nephrotoxicity or ototoxicity (such
as an aminoglycoside)

- 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;

- Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy at the time of registration;

- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note,
however, that laboratory tests for liver function and coagulation parameters are not
required for entry into this protocol.

- Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition;
note,however, that HIV testing is not required for entry into this protocol. The need
to exclude patients with AIDS from this protocol is necessary because the treatments
involved in this protocol may be significantly immunosuppressive. Protocol-specific
requirements may also exclude immuno-compromised patients.

- Pregnancy or women of childbearing potential and men who are sexually active and not
willing/able to use medically acceptable forms of contraception; this exclusion is
necessary because the treatment involved in this study may be significantly
teratogenic.

- Is pregnant; women of childbearing potential and male participants unwilling to
practice adequate contraception.