- To evaluate the rate of freedom from radical cystectomy at 3 years.
- 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.
- Carcinoma of the bladder pathologically (histologically or cytologically) diagnosed within the past 10 weeks, meeting either of the following criteria:
- Patients with operable tumors that are primary transitional cell carcinoma of the bladder exhibiting histologic evidence of invasion into the lamina propria (disease clinical stage T1) without evidence of muscularis propria invasion (muscularis propria must be present in the transurethral resection of the bladder tumor [TURBT] specimen) and are AJCC clinical stage T1, NX or N0, M0 without hydronephrosis
- Patients with disease involvement of the prostatic urethra with transitional cell carcinoma and have no evidence of stromal invasion of the prostate
- 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
- Must have a T1G2 or T1G3 transitional cell carcinoma that has recurred within 18 months after initial treatment for ≤ T1 tumors (TURBT and intravesical BCG immunotherapy) or have presented to a participating urologist who judged BCG therapy is contraindicated because patient may be immunocompromised
- 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
- Zubrod performance status 0-1
- WBC ≥ 4,000/mm^3
- 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 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)
Last updated: 09/26/2012
NCT ID: NCT00981656