Bladder CARETM
Non-invasive Bladder Cancer and UTUC
Early Detection and Surveillance Test
Bladder CARE™
Non-invasive, Early Bladder Cancer Detection and Surveillance Test
Non-invasive
Quantitative
Superior Accuracy
Fast Turnaround
Time
The Bladder CARE™ Assay has been granted FDA Breakthrough Device Designation for the following intended use:
Bladder cancer is the 4th most common cancer in men and there are over 80,000 new cases diagnosed annually within the USA. Non-muscle-invasive bladder cancer represents about 70% of all cases and generally has favorable survival outcomes, but with recurrence rates as high as 60 to 70%, intensive surveillance is necessary. Current guidelines recommend lifelong surveillance with cystoscopy, which is invasive, costly, and poses significant burdens on both the patient and the healthcare system. The cost of treatment and ongoing surveillance make bladder cancer the most expensive cancer to manage. Pangea Laboratory has developed a novel, non-invasive bladder cancer detection test that can significantly reduce the costs of patient diagnosis and monitoring.
Bladder CARE™ has a 93.5% sensitivity and a 92.6% specificity, demonstrating its accuracy in determining the likelihood of bladder cancer.
Since 2014, Pangea Laboratory has been working to provide the best non-invasive diagnostic tests to maximize the chance of treatment success for oncological patients. Bladder CARE™ is a completely non-invasive qPCR test for bladder cancer detection, using urine samples. The test measures the methylation level of three urothelial cancer-specific DNA biomarkers and two internal controls in a single qPCR reaction. Bladder CARE™ is a CE-marked IVD test for the urine-based detection of bladder cancer.
Bladder CARE™ can help streamline bladder cancer patient testing and surveillance for recurrence, with an easy-to-use and non-invasive at-home Urine Collection Kit. The highly sensitive test effectively detects the presence of both high- and low-grade bladder cancer tumors, facilitating surveillance for recurrence in patients with a history of bladder cancer. This makes it especially convenient and cost-effective for both patients and healthcare providers, by reducing the need for medical office visits while still allowing close monitoring of patients.
Bladder CARE™ can also significantly detect the presence of cancer cells at a minimum concentration of 0.046% cancer cells in urine samples, which is the equivalent of 1 cancer cell for every 2,200 normal cells. The low limit of detection (LOD) has important implications for not just early cancer detection, but potentially also the monitoring of tumor signals during and after treatments like neoadjuvant chemotherapy.
Contact Us for More Information
Non-Invasive Testing for the Early Detection of Bladder Cancer and UTUC
DNA methylation is an epigenetic mark that is often altered in human diseases including cancer, and it is believed that changes in DNA methylation are early events in tumorigenesis. It is believed that therefore, these epigenetic biomarkers promise to be good candidates for early tumor detection, especially when multiple methylation biomarkers are combined in a multiplex panel.
Bladder CARE™ measures the methylation level of three bladder cancer-specific DNA biomarkers: TRNA-Cys, SIM2, and NKX1-1. These loci are hypermethylated in both non-muscle-invasive bladder cancer and muscle-invasive bladder cancer and were discovered and validated as described in Clinical Epigenetics.
Using a proprietary algorithm developed by Pangea Laboratory, results are expressed as values on the Bladder CARE™ Index (BCI), which are proportional to the abundance of cancer DNA in the urine sample. Patients with a BCI < 2.5 are “negative” for the presence of bladder cancer, while patients with a BCI > 2.5 and > 5 are classified as “high-risk” and “positive”, respectively.
Clinical studies performed in collaboration with Zymo Research Corp. and with the participation of the Institute of Urology of USC Norris Comprehensive Cancer Center demonstrate that the Bladder CARE™ test has a sensitivity and specificity of 93.5% and 92.6%, respectively.
The Bladder CARE™ Test Process
Non-invasive at-home sample collection
Stabilization of Samples
Return sample to our laboratory
DNA is isolated and analyzed
Results provided within 72 hours
Step 1
Sample Collection and Stabilization
Urine samples for the Bladder CARE™ test can be collected comfortably at home, or at a medical facility, by using our Urine Collection Kit.
The ease of sample collection means this non-invasive screening option can be used at home by patients who require surveillance. It requires no special preparation, no need for patients to take time off, and no changes to their diet or medication.
Immediately after collection, urine samples must be stabilized using the Urine Preservation Reagent included in the Kit. This preserves the DNA at ambient temperatures for up to 30 days, allowing for the samples to be shipped to our lab.
Step 2
Sample Shipment with Pre-Paid Return Label
Step 3
DNA is Isolated and Analyzed with Bladder CARE™
After DNA is isolated from the urine sample, bladder cancer biomarkers are analyzed with Bladder CARE™ to provide accurate results.
Step 4
Results are Reported
Within 24 to 48 hours of receipt of the sample at our California-based laboratory, we will be able to securely deliver your test results to your doctor.
Our easy-to-interpret test report will indicate whether patients fall within the “negative”, “high risk” or “positive” categories.
View a Sample Report
“(the) Bladder CARETM test may be useful in monitoring and predicting response to neoadjuvant therapy in patients with muscle invasive bladder cancer.” – Saum Ghodoussipour, MD
The Science of Bladder CARE™
Bladder CARE™ Publications
A Urine-based DNA Methylation Marker Test to Detect Upper Tract Urothelial Carcinoma: A Prospective Cohort Study by Ghoreifi A., Seyedian S., Piatti P., et al (2023)
Clinical evaluation of Bladder CARE, a new epigenetic test for bladder cancer detection in urine samples by Piatti P., Chew Y., et al (2021)
Bladder CARE™ Abstracts, Posters and Presentations
Utility of a Urine-Based DNA Methylation Test for Surveillance in Non-Muscle Invasive Bladder Cancer: A Pilot Study by Ladi-Seyedian, S., Ghoreifi, A., et al (2022) – Presented at the American Urological Association General Meeting 2022, and won 3rd place at the Miley B. Wesson Resident Essay Contest t the Western Section American Urological Association 2022
A Urine-Based DNA Methylation Marker Test to Detect Upper Tract Urothelial Carcinoma: A Pilot Study by Ghoreifi, A., Ladi-Seyedian, S., et al. (2021) – Presented at the American Urological Association General Meeting 2021 and at the Western Section American Urological Association 2022
Urine Biomarkers for the Detection of Urothelial Carcinoma by Daneshmand, S. (2021) – Presented at Grand Rounds in Urology International Bladder Cancer Update 2021
A Urine-Based DNA Methylation Test to Monitor Response to Neoadjuvant Chemotherapy in Bladder Cancer by Ghodoussipour, S., Basin, M., et al. (2020) – Presented at the American Urological Association General Meeting 2020
Also available in Spanish and Portuguese
Bladder care epigenetic test allows the sensitive early detection of bladder cancer from urine samples by Piatti, P., Suwoto, M., et al. (2020) – Presented at Proceedings of the Annual Meeting of the American Association for Cancer Research 2020
Use of Biomarkers in Diagnostic Testing
DNA Methylation Cancer Biomarkers: Translation to the Clinic by Locke, W., Guanzon, D., et al. (2019)
Medical Policy: Urinary Tumor Markers for Bladder Cancer
BlueCross BlueShield of North Carolina
BlueCross BlueShield of New Mexico
While cystoscopy remains the gold standard to confirm the presence of bladder cancer and the first intervention procedure to remove the tumor, it is an invasive test that can often result in infections and other side effects. In contrast, Bladder CARE™ is completely non-invasive and has the potential to reduce unnecessary cystoscopies and medical office visits, while allowing more frequent surveillance of bladder cancer patients. Medical providers would also be able to better focus on the patients that most need attention. We envision that Bladder CARE™, along with the Urine Collection Kit, could be used as a front-line test for the detection of bladder cancer and the surveillance of those with a history of bladder cancer.
Bladder CARE™ is a Laboratory Developed Test (LDT), and we invite doctors and patients interested in learning more to get in touch with our team.
Pangea Laboratory is currently offering urologists and oncologists a six-month free trial of Bladder CARE™, so these medical professionals can assess its performance against current gold standards in diagnostics and patient monitoring. Contact us today for more information, and to join this program.
Important Safety Information and Product Limitations
Results should be interpreted by a trained professional in conjunction with the patient’s history and clinical signs and symptoms, and epidemiological risk factors. Results analysis and interpretation guidelines may be subjected to updates based on future clinical data.
False-negative results may arise from the improper collection, shipping, storage, and/or purification of the specimen. False-positive results may arise from the presence of tumors other than bladder cancer. The performance of this test was established using voided urine.
Negative results do not preclude bladder cancer and should not be the sole basis of a patient’s treatment/management or public health decision. Follow-up testing should be performed according to the healthcare provider’s recommendations.
Information provided by this test is for research purposes only.
Limitation of Procedures
Optimum performance of this kit requires urine specimens collected and stabilized in Urine Conditioning Buffer (Zymo Research, cat. D3061-1-140), extracted using the Quick-DNA Urine Kit (Zymo Research, cat. D3061) and analyzed using the Bio-Rad CFX96 Touch™ Real-Time PCR Detection System and the Bio-Rad CFX Maestro™ 1.1 Version 4.1.2433.1219 software (Bio-Rad). Variations in any component of the validation workflow indicated above may results in changes in performance characteristics of the Bladder CARE™ Kit.
Detection of bladder cancer-specific DNA may be affected by sample collection, stabilization, and extraction methods, patient factors, and/or stage of the disease. If you wish to use a different sample collection/preservation, extraction, and/or analysis system, please contact Zymo Research, and perform a cross-validation experiment.
A false negative result may occur if a specimen is improperly collected, transported, stored, handled and/or purified. False negative results may also occur if amplification inhibitors are present in the specimen or if inadequate numbers of cancer cells and/or DNA are present in the specimen.
False-positive results may arise from presence of tumors other than bladder cancer. The performance of this test was established using voided urine.
First-void, mid-stream, and first-morning urine, as well as urine collected from catheterized patients and tissue samples are also considered acceptable specimen, but performance has not been established.
Bladder CARE™ test failure may be caused by lubricating agents added to the urine samples during patient’s catheterization procedures, and by the presence of mucin in the sample at concentration at or above 0.1%. The impacts of drugs, anticancer treatments (including chemo- and immunotherapeutic agents), antibiotics, or immunosuppressant drugs on Bladder CARE™ test performance have not been evaluated.
Using less than 5 ng of DNA/reaction may increase the chance of inaccurate results as the number of DNA molecules analyzed may not be sufficient for accurate detection. DNA subjected to thermal or chemical denaturation is not compatible with Bladder CARE™ analysis. DNA isolated from samples treated with crosslinking agents (e.g. FFPE samples) is not compatible with Bladder CARE™ analysis.
To ensure the reproducibility of Bladder CARE™ test each real-time PCR instrument needs to be qualified with standard samples provided by Zymo Research Corp.
As with any molecular test, genomic mutations or deletions affecting the target regions detected by the Bladder CARE™ test could affect primer and/or probe binding resulting in failure to detect the presence of bladder cancer.
Results should be interpreted by a trained professional in conjunction with the patient’s history and clinical signs and symptoms, and epidemiological risk factors. Results analysis and interpretation guidelines may be subjected to updates based on future clinical data.
Negative results do not preclude bladder cancer and should not be the sole basis of a patient treatment/management or public health decision. Follow up testing should be performed according to healthcare provider’s recommendations.
Members of the testing laboratory will be trained to perform this assay and competency will be assessed and documented.
This test cannot rule out diseases caused by other types of cancer