Breakthrough in China's Cancer Early Screening: Large-Scale Prospective Cohort Study Data for Liquid Biopsy-Based Liver Cancer Screening Disclosed

In 2021, the cancer early screening market saw a comprehensive surge in industrial and capital interest, with products accelerating from the R&D phase into clinical translation.

Prospective cohort studies ensure product performance in real-world settings and are an essential pathway for the clinical translation of cancer early screening products.

Meanwhile, Chinese research institutions and enterprises are continuously exploring and achieving breakthroughs in the field of liquid biopsy for early cancer screening.

In March 2019, a study on early cancer screening, conducted collaboratively by the National Cancer Center, the Cancer Hospital of the Chinese Academy of Medical Sciences, and Genetron Holdings Limited, a precision medicine company, was published in PNAS. Coinciding with this milestone—the release of the first prospective cohort study on early liver cancer screening in China—HCCscreen made its debut.

Due to its excellent performance demonstrated in prospective cohort studies,In September 2020, HCCscreen achieved another milestone by receiving the U.S. FDA’s “Breakthrough Device” designation, becoming the first molecular diagnostic product from China to receive this recognition.

Six months later, on March 25, HCCscreen was completed once again.Latest Large-Scale Study on Prospective Cohort of Liquid Biopsy for Early Screening of Liver Cancer, the data are as follows:

As of February 2021, Genetron Holdings Limited completed follow-up visits for 1,615 patients who tested positive for hepatitis B surface antigen. The data shows that,HCCscreen achieved a sensitivity of 88% and a specificity of 93%.

It is worth noting the findings stratified by tumor size. Among patients diagnosed with liver cancer by HCCscreen, 49% were in the early stage, with tumors smaller than 3 cm; these patients are expected to have a significantly better prognosis than those with advanced-stage disease. For tumors smaller than 3 cm, the sensitivity of HCCscreen was 85%; for tumors measuring 3–5 cm, the sensitivity was 96%.

Globally, the number of cancer early screening products is increasing alongside booming market demand. Faced with a wide array of early screening options, verifying the true clinical value of these products has become a focal point. VCBeat evaluates the value of cancer early screening products by examining their registration and market approval processes, with a focus on clinical trial data, underlying technology development, and biomarker selection.

The regulatory approval and market launch pathway for early cancer screening products includes “underlying technology development – retrospective studies – prospective studies – regulatory approval and market launch.”

Among them, retrospective studies primarily focus on patients after diagnosis, with a small sample size and relatively low research difficulty, butRetrospective studies serve only as references during product development; they are prone to data bias in real-world applications and cannot accurately demonstrate the value of the product in early screening.

For example, in 2018, a prominent U.S. research team published findings on pan-cancer early screening in a top-tier journal. The study reported sensitivities ranging from 60% to 99% in a retrospective cohort, drawing significant attention from the industry. However, the same team later published results from a prospective cohort study using the same test kit, which showed a sensitivity of only 30%.

Therefore, for cancer early screening products to be applied in broader populations and achieve the status of “early screening”-grade products, they must undergo rigorous multicenter prospective cohort studies.The primary subjects of prospective cohort studies are high-risk populations without a confirmed diagnosis. These studies involve large enrollment sizes, substantial financial investment, and long follow-up periods, enabling them to simulate the real-world performance of cancer early screening products.

Many overseas cancer early screening companies have conducted multicenter prospective cohort studies.

Cologuard, a product of Exact Sciences, a pioneer in early colorectal cancer screening in the United States, also underwent multicenter prospective cohort studies before successfully launching on the market. Clinical trial results showed that Cologuard was more sensitive than FIT in detecting colorectal cancer and advanced precancerous lesions (adenomas and sessile serrated polyps). The detection rate for colorectal cancer was 92% vs. 74%, and the detection rate for adenomas was 42% vs. 24%.

Thrive, a multi-cancer early detection company, also announced the results of the world’s first prospective, international blood-based cancer screening study in 2020. The study involved 10,000 women with no prior history of cancer. By combining blood-based screening with routine screening methods, researchers were able to double the number of detected cancer cases and increase the screening specificity to 99.6%, building upon Thrive’s existing blood test technology, CancerSEEK.

Compared with foreign countries, China’s early cancer screening industry started later but is catching up rapidly by leveraging the country’s abundant sample populations and policy support, with the potential to achieve overtaking on a bend. In 2020, under the supervision and guidance of the National Medical Products Administration (NMPA), China’s first large-scale, multicenter, prospective registration clinical trial for early cancer screening was completed. Relying on this study, New Horizon Health’s colorectal cancer early screening product, “ColoClear,” successfully obtained market approval, filling a gap in the industry.

It is important to note that “Changweiqing” is based on fecal DNA testing and does not fall under the category of liquid biopsy technology. To date, no cancer early screening products in China’s liquid biopsy sector have been approved for market launch following validation through multicenter prospective studies; however, this field is by no means lacking in outstanding enterprises.

Genetron Holdings Limited is a leading player in China’s precision oncology sector, with cancer early screening as its key strategic focus. The company is developing liquid biopsy products for the early detection of liver cancer, lung cancer, and gastrointestinal cancers.

As early as 2019, Genetron Holdings Limited completed the world’s first prospective study on early screening for liver cancer., facilitating HCCscreen’s receipt of the FDA Breakthrough Device designation; in August 2020, Genetron Holdings Limited, in collaboration with the National Cancer Center and the Cancer Hospital of the Chinese Academy of Medical Sciences, launched ““R&D and Application of Early Screening and Diagnosis Technologies for High-Incidence Malignant Tumors,” thereby becoming the only company participating in national-level early screening R&D projects for three major cancer types (liver cancer, lung cancer, and gastrointestinal cancers); On March 25, the latest large-scale study data from a prospective cohort on liquid biopsy for early hepatocellular carcinoma screening were disclosed, further demonstrating Genetron Holdings’ strength in the field of cancer early screening.

Furthermore, based on the data from this large-scale, multicenter, prospective study on early screening for liver cancer, Genetron’s multicenter prospective study leads similar studies in terms of sample size, sensitivity, and specificity.

In addition to the multicenter prospective studies mentioned above, underlying technology development is also key to achieving breakthrough progress in cancer early screening products. Providing critical technical support for China’s largest-scale multicenter prospective early screening research projectMutation Capsuleis a major highlight.

Mutation Capsule technology is Genetron’s proprietary, independently developed liquid biopsy-based early cancer screening technology, based on multi-omics data,Only a small amount of blood is required to simultaneously detect methylation and multiple types of genetic mutations, including SNVs, Indels, and CNVs, enabling multiple tests on a single sample without compromising sensitivity.This technology has demonstrated excellent sensitivity and specificity in the early screening of liver cancer, lung cancer, and digestive system cancers.

Common biomarkers for early cancer screening include gene mutations, gene methylation, and protein markers. With technological advancements, the range of relevant targets continues to expand and update. Previously, early cancer screening was largely confined to single-omics approaches, with suboptimal sensitivity and specificity.

Cancer is a complex disease whose initiation and progression involve pathological processes across multiple levels and dimensions, including the genome, transcriptome, and proteome.Selecting more targets for multi-omics testing can effectively improve screening accuracy.

The advantages of multi-omics data in early cancer screening have been widely recognized by the industry. The accumulation and analysis of multi-omics, multi-dimensional data, along with model development, are considered the future direction for early cancer screening.

From the perspective of global corporate technological pathways, most established companies have adopted a strategy of multi-marker combined detection. Freenome integrates multi-omics analytical approaches with advanced computational biology and machine learning techniques, aiming to apply this technology to early screening for colorectal cancer. Exact Sciences’ product, Cologuard, detects seven gene mutations in KRAS, methylation of the NDRG4 and BMP3 genes, and β-actin. Thrive’s multi-cancer early detection product, CancerSEEK, employs multivariate analysis and nanobiotechnology to target 16 genes and 18 proteins directly associated with cancer, leveraging machine learning techniques for detection.

Multi-omics testing is hailed as the “next-generation liquid biopsy technology.” In the future, the cancer early screening industry will evolve toward a “multi-omics+” approach, integrating multi-dimensional data from metabolomics, microbiomics, and other fields to further advance precision early detection of cancer.

In recent years, the high incidence and mortality rates of cancer have made prevention and control an urgent priority, drawing significant attention from industry, research communities, and policymakers. During the 2021 “Two Sessions,” early cancer screening was frequently discussed. Li Zhaoshen, a member of the National Committee of the Chinese People’s Political Consultative Conference (CPPCC), an academician of the Chinese Academy of Engineering, and Director of the Department of Gastroenterology at Changhai Hospital affiliated with Naval Medical University, proposed launching nationwide community-based gastric cancer screening. Li Weimin, a deputy to the National People’s Congress (NPC) and President of West China Hospital of Sichuan University, recommended including early lung cancer screening in the national medical insurance coverage. Yu Jinming, also an NPC deputy and President of Shandong Cancer Hospital, advocated for the inclusion of general tumor screening in the medical insurance system.

The call by multiple attendees at the “Two Sessions” to prioritize early cancer screening has undoubtedly injected a “shot in the arm” into the industry, while also underscoring the urgent need for the development of more robust, high-quality products validated by prospective studies to meet substantial market demand.

After breaking through two key barriers—underlying technology R&D and forward-looking research—Genetron Holdings has further established the application pathway for its cancer early screening products, effectively ensuring product performance while also meeting the commercial requirements for large-scale promotion and adoption.

Multi-channel deployment is Genetron Holdings’ current business strategyCollaborations with health examination centers, government public welfare initiatives, and pharmaceutical companies, as well as the Laboratory Developed Tests (LDT) model, are all key components of its business blueprint. The company has already made significant industrialization moves across various channels.

Health examination centers are a critical channel for the implementation of early cancer screening products.In 2019, Genetron Holdings Limited partnered with iKang Guobin,Promote and provide early liver cancer screening test services through iKang Guobin’s nationwide network of health examination centers. Cancer early screening and health examinations primarily target healthy individuals and high-risk populations, creating natural synergies that can accelerate the commercialization of HCCscreen while helping iKang Guobin enrich its service offerings.

In 2020, HCCscreen was selected for the regional “Comprehensive Early Screening and Prevention and Control of Liver Cancer” demonstration project in Huishan District, Wuxi City, initiated by the People’s Government of Huishan District and guided by the National Cancer Center.With a population approaching 500,000 and a strong demand for cancer prevention, Huishan District has launched this project utilizing HCCscreen. The initiative aims to provide comprehensive screening and preventive services to 150,000 individuals at high risk for liver cancer within three years, delivering tangible technological benefits to the public. Furthermore, it seeks to establish Huishan as a model city for integrated early screening and prevention of liver cancer in China, with the goal of promoting this successful model nationwide.

In January 2021, Genetron Holdings Limited and Chia Tai Tianqing signed an exclusive strategic cooperation agreement in China for HCCscreen.Over the next three years, we will jointly promote HCCscreen in designated regions across China. As a leading enterprise in the field of botanical liver therapeutics in China, Chia Tai Tianqing possesses extensive hospital market resources for liver disease medications nationwide. By leveraging Chia Tai Tianqing’s advantages in the hospital sector, we aim to increase the penetration rate of HCCscreen and jointly safeguard the health of high-risk populations for hepatocellular carcinoma.

In February 2021, HCCscreen was included in the Guidelines for Patients with Primary Liver Cancer of the China Anti-Cancer Association.This is the first domestic guideline for the entire process of liver cancer prevention and treatment for patients, released by the China Anti-Cancer Association. HCCscreen is the only Chinese achievement in early liver cancer screening cited in this guideline. Under the guidance of the guideline, HCCscreen will benefit more high-risk populations for liver cancer.

However, it must be clear that market entry is not the end but the beginning of a new journey; the industrialization of early cancer screening faces significant challenges and remains a long-term endeavor. Customer price acceptance and performance recognition are critical issues that cannot be overlooked, requiring further engagement from policymakers, industry associations, and enterprises.

On the policy front, the government has introduced numerous favorable policies and actively spearheaded a wide range of public welfare cancer screening initiatives. On the association front, organizations such as the China Anti-Cancer Association have issued relevant guidelines to steer the industry toward rapid and standardized development. On the corporate front, Genetron Holdings Limited will leverage its multi-channel commercial footprint and broad coverage across multiple cancer types, working in close collaboration with policymakers and professional associations to continuously enhance the accessibility of early cancer screening products.