Radiation Therapy and Chemotherapy in Treating Patients With Stage I Bladder Cancer
Radiation Therapy and Chemotherapy in Treating Patients With Stage I Bladder Cancer
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. 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. Drugs used in chemotherapy, such as
 cisplatin, mitomycin C, and fluorouracil, work in different ways to stop the growth of tumor
 cells, either by killing the cells or by stopping them from dividing. Giving radiation
 therapy together with cisplatin may kill more tumor cells.

 PURPOSE: This phase II trial is studying how well radiation therapy given together with
 chemotherapy works in treating patients with stage I bladder cancer.
OBJECTIVES:

 Primary

 -  To evaluate the rate of freedom from radical cystectomy at 3 years.

 Secondary

 -  To evaluate the rate of freedom from radical cystectomy at 5 years.

 -  To evaluate the rate of freedom from the development of distant disease progression at 3
 and 5 years.

 -  To evaluate the rate of freedom from progression of bladder tumor to stage T2 or greater
 at 3 and 5 years.

 -  To evaluate disease-specific survival and overall survival.

 -  To evaluate the incidence of acute and late pelvic toxicity.

 -  To evaluate the efficacy of this treatment approach in preventing the recurrence of any
 local bladder tumor.

 -  To evaluate the potential value of tumor histopathology plus molecular genetic, DNA
 content, and urine proteomics parameters as possible significant prognostic factors for
 tumor control with this treatment approach.

 -  To collect American Urological Association symptom scores at baseline and at 3 years.

 OUTLINE: Beginning within 10 weeks of transurethral resection of the bladder tumor, patients
 undergo 3-dimensional conformal radiotherapy once daily 5 days per week during weeks 1-7 (34
 fractions). Patients also receive 1 of 2 radiosensitizing chemotherapy regimens concurrently
 with radiotherapy.

 -  Regimen I: Patients receive cisplatin IV on days 1-3 of weeks 1, 3, and 5.

 -  Regimen II: Patients receive mitomycin C IV on day 1 of radiotherapy and fluorouracil IV
 continuously over days 1-5 of weeks 1 and 4.

 Patients with a persistent tumor on re-evaluation may undergo radical cystectomy.

 Tissue, blood, and urine samples may be collected periodically for biomarker and other
 analysis.

 After completion of study treatment, patients are followed up every 3 months for 1 year,
 every 4 months for 1 year, every 6 months for 3 years, and annually thereafter.
DISEASE CHARACTERISTICS:

 -  Pathologically (histologically or cytologically) diagnosis of carcinoma of the bladder
 within 105 days prior to registration.

 -  Patients with operable tumors that are primary high grade urothelial carcinoma of
 the bladder exhibiting histologic evidence of invasion into the lamina propria
 (disease clinical stage T1) or a high grade stage Ta urothelial carcinoma without
 hydronephrosis.

 -  Patients with disease involvement of the prostatic urethra with urothelial
 carcinoma and have no evidence of stromal invasion of the prostate. If the
 patient's initial tumor was a high grade Ta urothelial carcinoma then his/her
 recurrent tumor must be a high grade stage T1 urothelial carcinoma to be
 eligible.

 -  Patients must have a high grade urothelial carcinoma stage Ta or T1 that has
 recurred within 540 days after completion of the initial treatment (transurethral
 resection bladder tumor [TURBT] and intravesical bacillus Calmette-Guerin [BCG]
 immunotherapy) or have presented to a participating urologist who judged BCG
 therapy is contraindicated because this patient may be immuno-compromised or
 because the patients refuses BCG therapy

 -  No confirmed tumor-related hydronephrosis

 -  No pN+ or > T1 disease

 -  No histologically or cytologically confirmed node metastases

 -  If radiologic evaluation of a lymph node is interpreted as "positive", this must
 be evaluated further either by lymphadenectomy or by percutaneous needle biopsy

 -  No evidence of distant metastases

 -  Patients for whom radical cystectomy is the standard next therapy per urologic
 guidelines, in the judgement of the participating urologist, are eligible

 -  Must have an adequately functioning bladder as judged by the participating urologist
 and radiation oncologist and have undergone a visibly complete re-staging TURBT by the
 participating urologist that shows (or is present on the outside pathology specimen) a
 T1G2 or T1G3 tumor with uninvolved muscularis propria in the specimen and, if on
 prostatic urethral biopsy mucosal carcinoma is present, there is no evidence on biopsy
 in the prostatic stroma of tumor invasion

 PATIENT CHARACTERISTICS:

 -  Zubrod performance status 0-1

 -  White blood cell count (WBC) ≥ 4,000/mm^3

 -  Absolute neutrophil count (ANC) ≥ 1,800/mm^3

 -  Platelet count ≥ 100,000/mm^3

 -  Hemoglobin ≥ 10.0 g/dL (transfusion or other intervention allowed)

 -  Serum creatinine ≤ 1.5 mg/dL

 -  Serum bilirubin ≤ 2.0 mg/dL

 -  Glomerular filtration rate (GFR) > 25 mL/min (for patients receiving cisplatin, GFR >
 60 mL/min)

 -  Not pregnant

 -  Negative pregnancy test

 -  Fertile patients must use effective contraception

 -  Able to tolerate systemic chemotherapy combined with radiotherapy and a radical
 cystectomy (if necessary), in the opinions of the urologist, radiation oncologist, and
 medical oncologist

 -  No prior or concurrent malignancy of any other site or histology (except for
 nonmelanomatous skin cancer, T1a prostate cancer, or carcinoma in situ of the uterine
 cervix) unless the patient has been disease-free for ≥ 5 years

 -  No severe, active co-morbidity including any of the following:

 -  Unstable angina and/or congestive heart failure that required hospitalization
 within the past 6 months

 -  Transmural myocardial infarction that occurred within the past 6 months

 -  Acute bacterial or fungal infection requiring IV antibiotics at the time of
 registration

 -  Chronic obstructive pulmonary disease exacerbation or other respiratory illness
 requiring hospitalization or precluding any study therapy at the time of
 registration

 -  Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

 -  AIDS based upon the current Centers for Disease Control definition (HIV testing
 not required)

 -  No prior allergic reaction to cisplatin, mitomycin, or 5-fluorouracil

 PRIOR CONCURRENT THERAPY:

 -  No prior systemic chemotherapy for bladder cancer

 -  Prior chemotherapy for a different cancer allowed

 -  No prior radiotherapy to the region of this cancer that would result in overlap of
 radiotherapy fields

 -  No concurrent drugs that have potential nephrotoxicity or ototoxicity (e.g.,
 aminoglycoside)