Prospective Multicentric Evaluation of a Bladder Preservation Strategy
Prospective Multicentric Evaluation of a Bladder Preservation Strategy
Radical cystectomy is the treatment of choice for bladder infiltrative urothelium carcinoma.
 But the removal of the bladder reservoir has a major impact of the Quality of life.
 Neoadjuvant chemotherapy has been shown to be associated with an absolute 5% survival
 benefit. Two monocentric studies suggest that this neoadjuvant chemotherapy could be used in
 combination with an optimal transurethral bladder resection, in a strategy of bladder
 preservation, provided a complete response being obtained (about 50% in every trial using
 neoadjuvant MVAC protocol before a radical cystectomy). In those both studies with patients
 T2 to T4, the 5 years overall survival is above 65%, with more than 40% bladder preservation
 rate at 5 years.

 The feasibility and the efficacy of such an attitude in a multicentric trail using the most
 active regimen (in term of complete response in metastatic patients) is unknown. The chosen
 regimen is therefore the intensified MVAC which allows, with the use of G-CSF, to double the
 dose-intensity of Adriamycin and Cisplatinum, and to decrease by 30% the methotrexate and
 vinblastine dose-intensity.

 The efficacy and safety confirmation of such an approach could lead to consider it in
 patients motivated to retain a functional bladder.
Every patient having signed the inform consent will have the following steps Maximal and
 optimal TURB using a standardized procedure. The TURB will always try to be optically
 complete.

 Neoadjuvant chemotherapy for 3 months with the intensified MVAC (6 cycles administered every
 2 weeks): METHOREXATE: 30 mg/m2 D1 - VINBLASTINE: 3 mg/m2 D2 - ADRIAMYCINE 30 mg/m2 D2 -
 CISPLATINE 70 mg/m2 D2. + G-CSF: 5 µg/kg from D4 to D10 New maximal standardized TURB at the
 end of the chemotherapy. In case of a lesion localized at the bladder dome, and if a maximal
 TURB appears to be unsafe, a partial cystectomy without lymph node dissection will be
 performed.

 If a complete response is obtained (no tumor cells in the bladder muscle on the last TURB), a
 surveillance will be proposed without any further treatment.

 Otherwise (tumor cells in the bladder muscle at the second TURB), a radical cystectomy will
 be done.

 If the balder is spared, the follow up will be as follow: clinical examination, CT, bladder
 endoscopy and urinary cytology every 6 months. The possible non muscle infiltrative bladder
 relapses will be treated according
Inclusion Criteria:

 -  T2 clinical stage (no palpable mass under anesthesia after TURB) Absence of diffuse
 Cis (Cis on random bladder biopsies) Patients above 18, and below 70 years of age PS
 status ≤ 2 No previous treatment for a bladder muscle infiltrative carcinoma. Previous
 endovesical instillations for non muscle infiltrative lesions (pTa, pT1, Cis) are
 allowed.

 No metastases on tauraco-abdomina-pelvic CT scan (no node > 1 cm) and bone scan.

 Normal biological values: neutrophils > 1,5.109 /l, platelets > 100. 109 /l, Alkaline
 Phosphatases < 2 x N, bilirubin < 1,5 N, Transaminases < 1,5 x N, Creatinine clearance ≥ 60
 ml/min Signed inform consent Patient belonging to a social security system.

 Exclusion Criteria:

 All other histology than urothelial carcinoma:

 -  primitive adenocarcinoma

 -  epidermoid carcinoma

 -  little cells carcinoma In situ diffuse carcinoma associated with urothelial carcinoma
 muscular infiltrating Tumor stade > T2, T3 or T4 or pT4a (prostatitis) Serious
 cardiac, pulmonary, hepatitic, renal, digestive or neurological pathology which is non
 equilibrating or potential aggravating risk by treatment Cancer history or other
 actual cancer (except skin cancer) not remission or with an end of treatment inferior
 to 2 years Participation to another clinical trial in a delay inferior to 30 days