Point of care, real-time urine metabolomics test to diagnose colorectal cancers and polyps in low- and middle-income countries

Colorectal cancer (CRC) has become a major public health issue in low- and middle-income countries (LMIC); globally, it is the third most common cancer. Colorectal cancer rates are rising in LMICs. Outcomes of patients with CRC are poor in LMICs, largely because patients have advanced disease. Colorectal cancer screening lowers mortality by identifying precancerous polyps (which can be removed) and diagnosing cancer at an early stage. In high-income countries (HIC), screening modalities include stool-based tests and endoscopies. Due to cost, high incidence of benign rectal bleeding, limited access, and lack of point of care (POC) options, these tests are rarely used in LMICs. The large majority of patients at high-risk for CRC in LMIC do not undergo any CRC testing. Thus, there is an unmet need for a cost-effective CRC diagnostic to identify patients at higher risk for CRC and polyps, thereby minimizing the number of costly negative colonoscopies. We propose using the research network we have built in Nigeria to implement a unique urine-based POC metabolomics test that can be performed in centers in LMICs to diagnose patients with early-stage CRC and/or precancerous polyps. Our goal is to validate our sensitive, affordable handheld biosensor device. We have shown that our 14-metabolite urine test sensitivity is 82.3% for polyp diagnosis and 95% for CRC diagnosis. During the UG3 phase, using urine from 450 Nigerian patients (150 with CRC, 150 with polyps, and 150 with normal colons), we will refine our metabolite signature to 3 metabolites and modify the biosensor to make it highly sensitive for Nigerian patients. During the UH3 phase, we will pilot test the biosensor device in Nigeria with 75 patients with CRC, polyps, and normal colons. We will then use the POC in real-time on urine from 645 patients >40 years of age with rectal bleeding, with a family history of CRC, or with a personal diagnosis of CRC. All patients will then receive a colonoscopy. Microcosting will be conducted to inform a cost-effective analysis, based on World Health Organization thresholds for cost-effective or very cost-effective, of the POC testing for each study group at the current projected price. Finally, we will determine beliefs and barriers related to urine testing for CRC. Our team is comprised of experts in CRC screening and management in HICs and LMICs (Memorial Sloan Kettering [MSK], Obafemi Awolowo University [OAU], and University of Alberta [UA]). Memorial Sloan Kettering and OAU have collaborated on 2 prospective studies. We also have experts in metabolomics, engineering, development of biosensor POC tests, and manufacturing and marketing of medical devices (UA and Metabolomics Technologies, Inc.). To ensure the device is appropriate for the Nigerian health system and global CRC guidelines, we have created an advisory committee with cancer care, CRC screening, and medical device development experts. Our POC biosensor will reduce CRC mortality in LMICs, where there are currently no alternatives.