Sample Collection for Ongoing Research and Product Evaluation Study - Non-muscle Invasive Bladder Cancer (SCORE-NMIBC)

The study is designed to evaluate the clinical performance of Natera's molecular residual disease (MRD) assays in detecting ctDNA in patients diagnosed with NMIBC. The goal is to assess the ability of the assay to identify minimal residual disease, monitor disease recurrence, and evaluate treatment response on therapy. No individual test results from the study testing will be provided to participants or their treating clinicians.

Participants who meet the study eligibility criteria will be invited to enroll in the study. Informed consent form (ICF) (paper or electronic) will be signed by the participant prior to study procedures. Participants will provide study-specific blood and urine samples at protocol defined timepoints.

The SCORE-NMIBC study includes two participant cohorts:

Cohort A - Intravesical Therapy and/or Systemic Therapy Cohort B - Cystectomy

Participants may be followed for up to three years, including up to two years of blood and urine collection and up to one year of data-only follow-up.

Tissue Sample Collection:

Residual tissue samples, collected as part of standard-of-care procedures, will also be obtained for study purposes.

Inclusion criteria

• Patient is at least 18 years of age or older.
• Eastern Cooperative Oncology Group performance status ≤ 2.
• Patient has a suspected high risk non-muscle invasive bladder cancer.

Note: The AUA/SUO risk stratification for primary non-muscle invasive bladder cancer will be used to determine high risk of tumor progression based on clinic and pathologic prognostic factors (Holzbeierlein et al., 2024):

• High grade T1.
• Any recurrent, High-grade TA.
• High grade TA, >3 cm (or multifocal).
• BCG failure in high grade patient.
• Any variant histology.*

*e.g. Micropapillary, plasmacytoid, small cell/neuroendocrine, and sarcomatoid histologies (in pure or mixed form with associated urothelial carcinoma)

• Any lymphovascular invasion.
• Any high grade prostatic urethral invasion.
• Meet the following criteria:

a. Cohort A: i. Participant has high risk ≤ T1 bladder cancer and is eligible for intravesical therapy or cystectomy. ii. Participant has been treated with intravesical and/or systemic therapy for high risk ≤ T1 bladder cancer and is entering surveillance. b. Cohort B i. Participant has high risk ≤ T1 bladder cancer and undergoing primary treatment with cystectomy. ii. Patients undergoing cystectomy following recurrence or progression of high risk ≤ T1 bladder cancer and where ≤ T1 bladder cancer is confirmed on cystectomy surgical pathology.

• Willing and able to tolerate blood draws according to Natera standard process.
• Willing to provide urine collection samples.
• Able to consent to and provide residual tumor tissue for research.
• Willing and able to comply with the study requirements.

Exclusion criteria

• Pregnant or breastfeeding.
• Prior history and treatment for any cancer (including muscle invasive bladder cancer) within the past year, or if they have any other active cancer, with the exception of participants who have undergone surgical removal of basal or squamous skin cancers, as well as those who have received NMIBC-directed therapy, including those undergoing cystectomy for primary NMIBC or after recurrence/progression of NMIBC.
• Diagnosis of >T1 bladder cancer at time of enrollment.
• Tumor tissue unavailable and/or consists only of carcinoma in situ (CIS) disease.
• At time of enrollment, has undergone or plans to undergo any ctDNA or utDNA testing to assess MRD, with the exception of one-time comprehensive genomic profiling for therapeutic drug selection.
• History of bone marrow or organ transplant.
• Serious medical conditions that may adversely affect ability to participate in the study.