Invasive bladder cancer is managed with neoadjuvant therapy followed by bladder removal (cystectomy). Research shows that approximately 40% of patient will have no remaining cancer left in their bladder after completion of the initial systemic treatment, and perhaps could have avoided the surgery. However, currently physicians lack the ability to identify these patients.
The investigators believe that by using advanced imaging (MRI), bladder biopsies and novel biomarkers that detect tumor DNA in blood, they can better identify participants without any remaining cancer after chemotherapy. This will make active surveillance of these participants safer. In this study, participants without evidence of residual cancer will be randomized to active surveillance vs conventional bladder treatment (bladder removal, or chemo-radiation of the bladder). This study will be a pilot randomized control trial (RCT), and if successful, it will transition to a larger phase 3 RCT.
Male or female >18 years
Primary urothelial or predominantly (>50%) urothelial carcinoma of the bladder with histologic evidence of muscularis propria invasion.
Clinical stage T2-T4aN0M0 (Radiographic lymphadenopathy greater than 1.5 cm in short axis by imaging must be proven by biopsy to be free of cancer)
No concomitant multifocal carcinoma in situ; a single focus is allowed.
Any component of small cell or plasmacytoid histology.
Prior systemic chemotherapy or immunotherapy (an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) or antibody-drug conjugate (NECTIN-4, HER2 or other) : Participants who have received any previous systemic therapy for urothelial carcinoma or cytotoxic chemotherapy, immunotherapy or other targeted therapy for another malignancy within 2 year of study entry are ineligible.
No available bladder tumor tissue from prior TURBT for tumor sequencing.
Prior or concurrent malignancy of any other site EXCEPT for non-melanoma skin cancer OR low risk malignancy not requiring treatment (such as prostate cancer Grade Group 1 under adequate surveillance, carcinoma in situ of the breast, cervix, etc.) AND unless free of disease for ≥ 5 years. Other cancers at low risk of recurrence may be allowed after review by principal investigator.
Parallel
Active Surveillance
Procedure/SurgeryParticipant found to have a cCR will be randomized to either standard of care or investigational active surveillance.
Control arm - Definitive bladder treatment
Procedure/SurgeryStandard of care, consisting of radical cystectomy or chemo-radiation of the bladder
Proportion of patients found to have a cCR and randomized on the number of patients enrolled (pilot-RCT ; phase 2)
Feasibility to randomized patients with cCR to either active surveillance or definitive bladder treatment.
Metastasis free survival at 2 years (phase 3)
Time to metastasis, defined as \>cN1 (more than 1 clinically suspicious lymph nodes), cT4a (unresectable disease), or M1 disease or death.
Bladder-intact event-free survival
Time from study entry to the earliest of histologically proven presence of MIBC (≥T2), clinical evidence of nodal or metastatic disease, radical cystectomy, or death due to any cause.
Proportion of cCR patient with ypT0
Rate of ypT0 (pathologic complete response) on cystectomy specimen following NAT in participants who had a cystectomy after identification of cCR.
Overall survival
Time from study entry to death; individuals who are alive at last contact will be censored on the date of last contact.
Acceptance rate to treatment allocation
Rate of concordance between treatment allocated and treatment received within the first 3 months following randomization.
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Peter Black
Lead sponsor
University of British Columbia
Sponsor institution
University of British Columbia
Collaborator
Canadian Institutes of Health Research (CIHR)
Collaborator
