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:

1. Age ≥ 18 years

2. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

3. Urothelial bladder cancer histologically proven (both pure urothelial cancers andmixed histologic features are allowed)

4. 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, abdomenand pelvis, either de novo or presenting first regional/distant relapse followingcystectomy (with no local recurrence in the cystectomy bed)

5. Completion of the initial phase (4-6 cycles) of 1st line metastatic treatment (systemic therapy by chemotherapy and/or immunotherapy by immune check-pointinhibitor according to standard recommendations). Patients having startedmaintenance therapy are eligible.

6. No disease progression after the initial phase of first-line metastatic systemictherapy according to RECIST v1.1

7. No more than 3 residual distant metastatic lesions following the initial phase offirst-line metastatic systemic therapy:

8. Regional nodes (below aortic bifurcation) are not included in the count ofdistant metastatic lesions

9. The number of distant residual lesions is determined on the basis of theimaging modality for tumor response assessment performed after systemictreatment according to local habits (CT-scan or 18FDG PET-CT if performed):In case of response assessment by CT-scanner only: residual lesions are allremaining visible lesions In case of response assessment by additional 18FDGPET-CT: residual lesions are only the lesions with residual hyperfixation

10. Regarding distant lymph nodes metastases:

• If evaluation is performed by CT-scanner only, residual lymph nodes areconsidered pathological according to one or several criteria among: Shortaxis ≥ 1cm/Central necrosis/Heterogeneous contrast enhancement
• Residual para-aortic nodes involvement accounts for one lesion, even ifseveral para-aortic nodes are involved.
• Other nodes: each involved node accounts for one lesion.

8. Residual distant metastases (if applicable) eligible for SBRT in terms of doseconstraints to the organs at risk, with no prior radiotherapy interfering with SBRT

9. 8 weeks or less between last cycle of the initial phase of systemic treatment andrandomization

10. No contraindication to pelvic radiotherapy

11. Signed informed consent

12. Patient able to participate and willing to give informed consent prior performanceof any study-related procedures and to comply with the study protocol

13. Patient affiliated to a Social Health Insurance in France

Exclusion Criteria:

1. Non-transitional cell histology (Squamous cell carcinoma, adenocarcinoma orneuroendocrine carcinoma of the bladder)

2. Brain metastases before systemic treatment

3. Liver metastases before systemic treatment

4. Absence of target to be irradiated (i.e. previous cystectomy + no residual distantlesions following systemic treatment + no pelvic or para-aortic nodes at metastaticpresentation)

5. Patient with relapse following definitive chemoradiation of the bladder

6. Local recurrence in the cystectomy bed following cystectomy

7. Previous pelvic irradiation

8. Prior radiotherapy near the residual metastatic lesions precluding ablative SBRT

9. Active inflammatory bowel disease

10. Contraindication to SBRT of a lesion due to organ dysfunction; in particular,patients with lung lesions and documented or suspected interstitial lung diseaseshould not be included

11. History of scleroderma

12. Current or past history of second neoplasm diagnosed within the last 5 years (exceptbasocellular carcinoma and prostate cancer incidentally discovered during previouscystoprostatetectomy and pelvic lymph node dissection and with a good prognosis [Tstage <pT3b and Gleason <8 and pN- and post-operative PSA <0.1 ng/mL])

13. Pregnancy or breast feeding or inadequate contraceptive measures

14. Known psychiatric or substance abuse disorders that would interfere with cooperationwith the requirements of the trial.

15. Any psychological, familial, geographic or social situation, according to thejudgment of investigator, potentially preventing the provision of informed consentor compliance to study procedure

16. Patient who has forfeited his/her freedom by administrative or legal award or who isunder legal protection (curatorship and guardianship, protection of justice).

17. Concurrent enrolment in another interventional therapeutic clinical study