A Phase II Trial Evaluating an Organ-conserving Strategy by Radiochemotherapy for Muscle-infiltrative Bladder Cancer

A Randomized Phase II Trial Evaluating an Organ-conserving Strategy With Radiotherapy + CDDP + Gemcitabine vs Radiotherapy + CDDP in 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