Consolidative Radiotherapy for Metastatic Urothelial Bladder Cancer Patients Without Progression and With no More Than Three Residual Metastatic Lesions Following First Line Systemic Therapy: a Prospective Randomized Comparative Phase II Trial
This is a Phase II, multicenter, randomized open-label and comparative study that has been designed to evaluate whether local consolidative radiotherapy in addition to standard of care improves overall survival as compared with standard of care in patients with regional and/or distant metastatic urothelial bladder cancer who have no disease progression and with no more than three residual distant metastatic lesions following the initial phase of first-line systemic therapy. Each patient will be followed during 4 years from the date of randomization.
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Urothelial bladder cancer histologically proven (both pure urothelial cancers and mixed histologic features are allowed)
• Metastatic patients to regional nodes (Tx,N1-N3,M0) and/or distant sites (Tx,Nx,M1a-M1b) documented with contrast-enhanced CT-scanner of the chest, abdomen and pelvis, either de novo or presenting first regional/distant relapse following cystectomy (with no local recurrence in the cystectomy bed)
• Completion of the initial phase (4-6 cycles) of 1st line metastatic treatment (systemic therapy by chemotherapy and/or immunotherapy by immune check-point inhibitor according to standard recommendations). Patients having started maintenance therapy are eligible.
• No disease progression after the initial phase of first-line metastatic systemic therapy according to RECIST v1.1
• No more than 3 residual distant metastatic lesions following the initial phase of first-line metastatic systemic therapy:
∙ Regional nodes (below aortic bifurcation) are not included in the count of distant metastatic lesions
‣ The number of distant residual lesions is determined on the basis of the imaging modality for tumor response assessment performed after systemic treatment according to local habits (CT-scan or 18FDG PET-CT if performed):
∙ In case of response assessment by CT-scanner only: residual lesions are all remaining visible lesions In case of response assessment by additional 18FDG PET-CT: residual lesions are only the lesions with residual hyperfixation
‣ Regarding distant lymph nodes metastases:
⁃ If evaluation is performed by CT-scanner only, residual lymph nodes are considered pathological according to one or several criteria among: Short axis ≥ 1cm/Central necrosis/Heterogeneous contrast enhancement
• Residual para-aortic nodes involvement accounts for one lesion, even if several para-aortic nodes are involved.
• Other nodes: each involved node accounts for one lesion.
• Residual distant metastases (if applicable) eligible for SBRT in terms of dose constraints to the organs at risk, with no prior radiotherapy interfering with SBRT
• 8 weeks or less between last cycle of the initial phase of systemic treatment and randomization
⁃ No contraindication to pelvic radiotherapy
⁃ Signed informed consent
⁃ Patient able to participate and willing to give informed consent prior performance of any study-related procedures and to comply with the study protocol
⁃ Patient affiliated to a Social Health Insurance in France