Advances in Next-Generation DNA Sequencing and Machine Learning Enable Rapid Analysis of Genetic Mutations to Determine Cancer Risk
CHICAGO – May 1, 2023 – A new genomic urine test can help doctors accurately predict bladder cancer as many as 12 years before clinical signs and symptoms emerge and long before a diagnosis can be made with cystoscopy, the most common method of detection, according to a new study* presented here at the 2023 American Urological Association (AUA) Annual Meeting.
Developed by Convergent Genomics, the UroAmp test uses next-generation DNA sequencing and machine learning to analyze urine for mutations across 60 genes linked to bladder cancer while also measuring the entire genome. In the study, a team of American, French and Iranian researchers focused on a subset of 10 genes that hold the greatest predictive power for a future bladder cancer diagnosis. Funding for the study was provided by the National Cancer Institute through a Small Business Innovation Research (SBIR) grant to Convergent Genomics.
“This is the first study to show comprehensive genomic profiling of somatic mutations can detect preclinical urothelial cancer more than a decade ahead of a natural diagnosis,” said Yair Lotan, MD,** study co-author and Professor of Urology and Chief of Urologic Oncology at University of Texas (UT) Southwestern Medical Center in Dallas. “With further studies, this discovery could improve how we identify, risk stratify and monitor patients at increased risk of developing bladder cancer.”
Researchers studied UroAmp in two ways. First, they conducted a case-control study with urine samples from 96 control subjects and 70 bladder cancer patients (22 de novo, 48 surveillance). This found UroAmp had an 86% sensitivity in predicting new tumors and 71% sensitivity overall (new and recurrent). Specificity, or the percentage of people who tested negative for bladder cancer and do not have the disease, was 94%.
A second study used a nested case-control design within the prospective Golestan Cohort Study, which contains urine samples from over 50,000 patients taken up to 12 years ago. Researchers analyzed the urine from 29 patients who developed bladder cancer and compared it to 98 control subjects who never developed the disease. UroAmp correctly predicted future cancer in 66% of cases with a 94% specificity. When limited to patients who were diagnosed within five years from initial urine collection, UroAmp sensitivity jumped to 90%.
“Somatic mutations can be acquired over years and give rise to tumors through diverse combinations of gene dysregulation. By uncovering the unique genetic fingerprint of each cancer, we will learn to better define genetic risk and personalize cancer care,” said Keyan Salari, MD, PhD, study co-author and Assistant Professor of Urology at Harvard Medical School and Massachusetts General Hospital. “The detection lead time afforded by this approach has promising diagnostic potential and identifies a whole new group of individuals potentially eligible for increased screening or studies of chemoprevention.”
The American Cancer Society estimates more than 82,000 people in the U.S. will get urothelial carcinoma (bladder cancer) this year alone and over 16,700 will die from the disease. More than 700,000 people currently live with bladder cancer, which has a recurrence rate of 60% to 70%. Early detection is key so that treatment may be provided before the cancer becomes invasive. Bladder cancer has one of the highest average life-long per-patient surveillance costs of any solid cancer.
“These exciting findings continue to lay the groundwork towards a whole new molecular paradigm in the diagnosis of bladder cancer,” said study co-author Trevor Levin, PhD, Founder and CEO, Convergent Genomics. “By leveraging the latest machine learning and next-generation DNA sequencing, we can non-invasively measure with exceptional accuracy the mutations acquired in bladder cells over our lifetimes. Imagine the potential benefits to quality of life and the healthcare system if people at the highest genomic risk of cancer are identified a decade before the disease will clinically manifest. This discovery could open the ultimate window of opportunity for highly targeted screening, therapeutic and behavioral cancer prevention.”
Previous studies have shown UroAmp’s comprehensive genomic approach is more accurate than other methods of detection and monitoring and provides greater insights into a patient’s prognosis and risk of recurrence than cystoscopy alone. UroAmp may be administered at home or in a healthcare setting and is analyzed at Convergent’s CLIA-certified lab in South San Francisco, where the comprehensive genomic profile and risk assessment are developed.
About Convergent Genomics
Convergent Genomics was founded in 2015 by a team of cancer biologists, urologic oncologists, and data scientists in partnership with Oregon Health & Science University (OHSU) and Illumina Accelerator. The company has received multiple peer-review grants from the National Cancer Institute and is engaged in research with over 30 sites worldwide, including leading academic centers. Convergent Genomics operates clinical laboratories in South San Francisco that are certified by the California Department of Public Health and nationally by CLIA-CMS. The company’s first product, UroAmp, has been available in limited release since 2021. For more information, visit www.convergentgenomics.com.
*Urinary comprehensive genomic profiling predicts urothelial cancer up to 12 years ahead of clinical diagnosis: an expanded analysis of the Golestan Cohort Study
Yair Lotan, Keyan Salari, Adam S. Feldman, Debasish Sundi, Jason J Lee, Gabrielle DiFiore, Hossein Poustchi, Masoud Khoshnia, Gholamreza Roshandel, Arash Etemadi, Mahdi Goudarzi, Peter S. Lentz, Kevin G. Phillips, Vincent T. Bicocca, Theresa M. Koppie, Joe W. Gray, Trevor G. Levin, Reza Malekzadeh, Mahdi Sheikh, Florence Le Calvez-Kelm
**Consultant to Convergent Genomics