Consolidative Radiotherapy for Metastatic Urothelial Bladder Cancer Patients Without Progression and With no More Than Three Residual Metastatic Lesions Following First Line Systemic Therapy

Inclusion criteria

• 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

Exclusion criteria

• Non-transitional cell histology (Squamous cell carcinoma, adenocarcinoma or neuroendocrine carcinoma of the bladder)
• Brain metastases before systemic treatment
• Liver metastases before systemic treatment
• Absence of target to be irradiated (i.e. previous cystectomy + no residual distant lesions following systemic treatment + no pelvic or para-aortic nodes at metastatic presentation)
• Patient with relapse following definitive chemoradiation of the bladder
• Local recurrence in the cystectomy bed following cystectomy
• Previous pelvic irradiation
• Prior radiotherapy near the residual metastatic lesions precluding ablative SBRT
• Active inflammatory bowel disease
• Contraindication to SBRT of a lesion due to organ dysfunction; in particular, patients with lung lesions and documented or suspected interstitial lung disease should not be included
• History of scleroderma
• Current or past history of second neoplasm diagnosed within the last 5 years (except basocellular carcinoma and prostate cancer incidentally discovered during previous cystoprostatetectomy and pelvic lymph node dissection and with a good prognosis [T stage <pT3b and Gleason <8 and pN- and post-operative PSA <0.1 ng/mL])
• Pregnancy or breast feeding or inadequate contraceptive measures
• Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Any psychological, familial, geographic or social situation, according to the judgment of investigator, potentially preventing the provision of informed consent or compliance to study procedure
• Patient who has forfeited his/her freedom by administrative or legal award or who is under legal protection (curatorship and guardianship, protection of justice).
• Concurrent enrolment in another interventional therapeutic clinical study