This pilot feasibility clinical trial is evaluating a novel treatment strategy for patients with advanced bladder cancer that is unresectable, has spread to nearby lymph nodes or a limited number of distant sites (oligometastatic disease), and has responded to initial treatment with enfortumab vedotin and pembrolizumab. Although this combination has significantly improved outcomes compared to traditional chemotherapy, many patients are left with residual cancer in the bladder or other sites, and there is currently no established standard approach for managing this remaining disease or determining the optimal duration of systemic therapy. Prolonged treatment can lead to cumulative side effects and negatively impact quality of life.
This study investigates whether adding consolidative treatment-such as radiation therapy to the bladder and metastatic sites or surgical removal of the bladder (radical cystectomy)-can safely eliminate residual disease and delay cancer progression. Radiation therapy uses high-energy x-rays to precisely target and destroy cancer cells while minimizing exposure to surrounding normal tissues. In selected patients, surgery may be used to remove remaining tumor in the bladder. Targeted radiation techniques, such as stereotactic body radiation therapy (SBRT), may also be used to treat small metastatic sites. This approach may allow for safe discontinuation of systemic therapy, potentially reducing long-term treatment-related side effects.
A key component of this trial is the integration of biomarker testing using circulating tumor DNA (ctDNA) from blood and urine tumor DNA (utDNA). These tests detect small amounts of tumor-derived genetic material and may help identify patients most likely to benefit from consolidative treatment, as well as guide decisions about ongoing therapy. By combining response to systemic therapy with personalized local treatment and biomarker-driven monitoring, this study aims to improve cancer control, reduce complications from untreated local disease, and inform future treatment strategies for patients with advanced bladder cancer.
Age >= 18 at the time of screening
Ability to understand and willingness to sign a written informed consent document
Histopathologically confirmed cTxN1-3M0, cTxNxM1 or cT4bNxM0 muscle invasive bladder cancer at initial diagnosis
Achieved a radiographic complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria and at the determination of treating physicians) after 3-9 cycles of induction EV + pembro
Prior radiation therapy with field overlapping with current proposed radiation field, precluding delivery of meaningful dose of radiation
Intracranial metastasis
Any small cell component, or predominant (> 50%) sarcomatoid or plasmacytoid histology
Other active malignancy or clinically relevant malignancy within past 2 years, per discussion with the principal investigator
Single group
Intensity-Modulated Radiation Therapy
RadiationUndergo IMRT
Volume Modulated Arc Therapy
RadiationUndergo VMAT
Radiosensitizing Agent
DrugGiven radiosensitizing chemotherapy
Radical Cystectomy
Procedure/SurgeryUndergo radical cystectomy
Pelvic Lymphadenectomy
Procedure/SurgeryUndergo pelvic lymph node dissection
Stereotactic Body Radiation Therapy
RadiationUndergo SBRT
Computed Tomography
Procedure/SurgeryUndergo CT and/or PET/CT
Positron Emission Tomography
Procedure/SurgeryUndergo PET/CT
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Transurethral Resection of Bladder Tumor
Procedure/SurgeryUndergo re-TURBT
Cystoscopy
Procedure/SurgeryUndergo cystoscopy
Biospecimen Collection
Procedure/SurgeryUndergo collection of blood and urine samples
Questionnaire Administration
Other interventionAncillary studies
Completion rate of protocol-defined treatment (feasibility)
Feasibility will be assessed through the completion rate of protocol-defined treatment. Primary endpoint is met if the completion rate of protocol-defined treatment is \> 70%. Descriptive statistics will be provided.
Progression-free survival
The Kaplan-Meier method will be used.
Incidence of treatment-related grade 3 or higher adverse events
Safety of consolidative radiation therapy will be assessed by the incidence of treatment-related grade 3 or higher toxicities per Common Terminology Criteria for Adverse Events version 6 that is possibly, probably, or definitely related to radiation treatment or chemoradiation therapy. Descriptive statistics will be provided.
Change in patient-reported quality of life
Changes in patient-reported quality of life will be measured by the Functional Assessment of Cancer Therapy-Bladder (FACT-Bl) assessment. Will measure change in total FACT-Bl score from baseline to each follow-up assessment as well as changes in individual domain subscale scores (physical, social/family, emotional, functional well-being, and bladder-specific concerns). Each question is scored 0-4 and higher score indicates better quality of life (for negatively worded items \[e.g., symptoms, distress\], scores are reversed). Clinically meaningful deterioration or improvement will be defined using established minimally important difference thresholds for FACT-Bl.
Time to progression in the bladder (local control)
The Kaplan-Meier method will be used.
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University of Washington
Lead sponsor
Lopker Family Foundation
Collaborator
