A Phase II Trial Evaluating an Organ-conserving Strategy by Radiochemotherapy for Muscle-infiltrative Bladder Cancer
A Phase II Trial Evaluating an Organ-conserving Strategy by Radiochemotherapy for Muscle-infiltrative Bladder Cancer
If radical cystectomy remains the standard of care for muscle invasive bladder cancer,
 consequences of this surgical procedure are often harsh. Over the past years, concurrent
 chemo-radiotherapy has imposed itself as an alternative treatment. Published data on
 concomitant radiochemotherapy (radiotherapy/cisplatin or
 radiotherapy/cisplatin/5-fluorouracil combinations) showed local control rates with bladder
 preservation at 5 years ranging from 40% to 65% according to the disease stage, and overall
 survival probabilities ranging from 40% to 50% at 5 years. In order to improve local and
 systemic prognosis, evaluation of other chemotherapy agents with higher radiosensitizing
 effect, such as gemcitabine, is justified. Gemcitabine possesses its own anti-cancer
 activities on urothelial diseases and has a synergetic activity with cisplatin. The
 investigators completed a monocenter phase I study combining radiotherapy, cisplatin, and
 twice-weekly gemcitabine, and determined a recommended dose of gemcitabine 25 mg/m². The
 objective of the present study is to evaluate the combination of radiotherapy + cisplatin +
 gemcitabine in terms of disease-free survival in non metastatic muscle invasive urothelial
 cancer patients.
The objective of the present study is to evaluate the combination of radiotherapy + cisplatin
 + gemcitabine in terms of disease-free survival in non metastatic muscle invasive urothelial
 cancer patients.
Inclusion Criteria:

 -  Muscle invasive urothelial cancer (front line or following the progression of a
 superficial tumor), pT2-pT3 stage without lymphatic impairment (N0) and without
 detectable metastases (M0). An optimal macroscopic resection (TURB) have to be
 performed

 -  The proof of invasive tumor to the muscle should be brought by a transurethral
 resection under anaesthesia less than 8 weeks before or, in the absence, by
 superficial biopsies and formal imaging. Multiples biopsies in the bladder must also
 be performed.

 -  Age ≥ 18 years

 -  Life expectancy ≥ 6 months

 -  Kanorfsky index ≥ 70 % (WHO 0, 1, 2)

 -  Biological criteria: neutrophils ≥ 1500/mm3, Platelets ≥ 100 000/mm3, haemoglobin ≥ 10
 g/dl, creatinine clearance > 60 ml/mn

 -  No distant metastases (Thorax, abdomen, and pelvic CT-scan, bone scan)

 -  Efficient contraception for premenopausal women, maintained during the whole treatment
 and up to two months after the completion of radiotherapy.

 -  No radiotherapy or chemotherapy history except for in situ bladder lesions.

 -  No carcinological history except for non melanoma skin tumours, in situ uterine cervix
 cancer

 -  No contraindication to gemcitabine or cisplatin.

 -  No contraindication to radiotherapy

 -  Information letter and informed consent signed

 -  Patient covered by social security

 Exclusion Criteria:

 -  Bladder tumors without any muscle infiltration

 -  Epidermoid carcinoma or adenocarcinoma

 -  Distance metastases or extrapelvic node positivity

 -  Severe digestive history (ulcerative colitis, complicated diverticulitis)

 -  Pregnancy and breast feeding