Adjuvant Radiotherapy in Patients With Pathological High-risk Bladder Cancer (GETUG-AFU 30)

Prior treatment

• Patients with R1 resection and with orthotropic neo-bladder reconstruction as urinary diversion are not eligible.
• Prior pelvic radiotherapy.
• Prior chemotherapy for other malignant diseases within the previous 5 years, except for neoadjuvant pre-cystectomy chemotherapy or adjuvant chemotherapy which are permitted.
• Patients enrolled in another therapeutic study within 30 days prior of randomisation.

Other illness

• Patients with clinical or radiological evidence of metastases or N3 staged bladder cancer are not eligible.
• Prior invasive solid tumours or haematological malignancies unless disease free for a minimum of 3 years prior to randomisation except:
  • skin basal cell carcinoma,
  • in situ epithelioma of the cervix,
  • or prostate cancer: incidentally discovered during cystoprostatectomy and pelvic lymph node dissection and with a good prognosis (T stage \<pT3b and/or Gleason \<8 and pN- and/or post-operative prostate-specific antigen (PSA) \<0.1 nanogram/mL),
• Patients with active inflammatory bowel disease.
• Patients who required surgical treatment for bowel obstruction before bladder cancer diagnosis or after cystectomy.
• Patients with any other disease or illness which requires hospitalization or is incompatible with the study treatment are not eligible.

Lab values

• Patients with the following severe acute co-morbidity are not eligible:
  • Unstable angina or congestive heart failure that required hospitalization in the 6 months before randomisation.
  • Transmural myocardial infarction in the 6 months prior to randomisation.
  • Acute bacterial or fungal infection requiring intravenous antibiotics at randomisation.
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of randomisation.
  • Severe hepatic disease: Child-Pugh Class B or C hepatic disease.
  • Known acquired immune deficiency syndrome (AIDS); the study treatment could impact blood count.

Other

• Patient must not be enrolled if he/she fulfils any of the following non-inclusion criteria:
• Patients unable to comply with study obligations for geographic, social, or physical reasons, or who are unable to understand the purpose and procedures of the study.
• Person deprived of their liberty or under protective custody or guardianship.

• To be eligible, the patients must fulfil all of the following inclusion criteria:
• Patients with histologically-confirmed muscle-invasive bladder cancer, either with pure urothelial carcinomas, or dominant urothelial carcinomas (\>50%) combined with other histological variants including: micropapillary, epidermoid, or adenocarcinomas, are eligible. Patients with small cell variants, pure adenocarcinomas, or pure epidermoid carcinomas are not eligible.
• Patients with radical cystectomy and pelvic lymph nodes dissection with no microscopic residual disease (R0 and R1).
  • Note that only R1 patients without urinary diversion as orthotropic neo-bladder replacement are eligible for the study, to limit cystectomy bed radiation induced toxicities.
• Patients with tumours of TNM staging: pN0-2, M0 by imagery, and pT3a, pT3b, pT4a, and pT4b, as well as, pTX-pN1-2, pTX-NX-R1 are eligible.
• Patients having received neo-adjuvant or adjuvant chemotherapy treatment are eligible. Randomization is allowed only if AE due to chemotherapy are ≤grade 2 at randomization.
• Patients ≥18 years old.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• Absolute neutrophil count (ANC) ≥1500 cells/mm³.
• Platelets ≥100000 cells/mm³.
• Haemoglobin ≥8 g/dL (Note: following a blood transfusion or another intervention if required).
• Adequate hepatic function: aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) ≤2.5 x upper limit of normal (ULN); or ≤3.5 x ULN in the case of concurrent disease with known etiology and for which a corrective treatment is possible.
• Adequate renal function: clearance \>30 mL/min (MDRD).
• Patients having provided written informed consent prior to any study-related procedures.
• Patients affiliated to the social security scheme.
• Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.