May 19, 2024

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The age of genomics in cancer screening: Enabling earlier cancer detection

The age of genomics in cancer screening: Enabling earlier cancer detection



The age of genomics in cancer screening: Enabling earlier cancer detection.  Why achieve earlier detection?




Researchers are unlikely to find a cure for cancer in monotherapy. In fact, the most effective way to fight cancer may not be treatment at all, because “an ounce of prevention is better than a pound of cure.” This article aims to quantify how prevention affects cancer mortality.



Why achieve earlier detection?

Cancers that are diagnosed early are easier to treat. All solid tumors are benign lesions called tumor-like hyperplasia at the beginning, from local to regional, and finally to distant or metastatic cancer. With the development of cancer, treatment options are also decreasing, surgeons lose the opportunity to completely remove the tumor, and chemotherapy becomes ineffective. Unfortunately, for many patients, symptoms do not appear until the cancer has spread. Take lung cancer, pancreatic cancer, and ovarian cancer as examples. Most tumors have metastasized when they are diagnosed. Over time, metastatic cancer only accounts for a small number of new cases, but it causes most deaths, as shown in the figure below.


The age of genomics in cancer screening: Enabling earlier cancer detection

Source: ARK Investment Management LLC, 2020

The basic principle of screening is that cancer follows a predictable path-from a localized, treatable cancer to a metastatic, deadly cancer. Conceptually, early detection can maximize the availability of existing treatments and interventions before the cancer becomes uncontrollable. Although ARK believes that treatment will improve for advanced cancer, these drugs are unlikely to cure cancer and may be too individualized to benefit only a small number of patients. Therefore, designing a powerful tool to detect cancer at an early stage and reduce cancer mortality is essential for a large number of people in the world.



Current screening standards

The United States Preventive Services Task Force (USPSTF) is an independent coalition of doctors, medical scholars and policy makers that regularly publishes national cancer screening guidelines. Since its establishment in 1984, the US Preventive Services Task Force has only issued screening recommendations for breast, cervical, and colorectal cancers. In the absence of more formal guidance, doctors usually screen for liver cancer, lung cancer, and prostate cancer.

Today, almost all screening technologies have a history of half a century, and in the context of recent scientific breakthroughs, these technologies have defects. For example, medical imaging techniques such as breast imaging and low-dose CT (LDCT) scans are highly sensitive but have poor specificity, which means false positives, as described below. In addition, they are limited to certain parts, not the entire body. Common proteomic biomarkers used to screen tumors-including carcinoembryonic antigen (CEA), prostate specific antigen (PSA) and cancer antigen 125 (CA-125), their sensitivity-specific characteristics and detectability The types of cancer are also limited.


The age of genomics in cancer screening: Enabling earlier cancer detection

Source: ARK Investment Management LLC, 2020


Due to limited accuracy, low resolution, and misunderstandings, many doctors and patients are hesitant to follow the guidelines of the National Cancer Screening Health Organization. Colonoscopy is a semi-invasive test to detect colorectal cancer. Some patients who are eligible for colonoscopy avoid the examination because they are worried that the colonoscopy itself will cause harm or produce false results. Therefore, many professionals in the medical field are pessimistic about the prospects of cancer screening.
We believe that traditional screening tools can achieve earlier cancer detection. On the contrary, liquid biopsy, as a molecular detection method that combines decades of genome research, cutting-edge machine learning, and synthetic biology, is likely to become the cutting-edge technology for cancer screening, because the technology is already very advanced and the cost has dropped to a critical value.




Cancer screening in the post-genomic era

The Human Genome Project (HGP), which ended in 2003, marked the beginning of the post-genome era. In our opinion, genomics is the basis of personalized medicine, making it possible to treat each individual’s unique gene mutations.

Cologuard of Exact Sciences (EXAS) was approved by the FDA in 2014 and initiated colorectal cancer (CRC) screening in the post-genomic era. Cologuard, which was mailed to the patient’s home, was able to find information about the genetic abnormality of the fecal tumor. In addition, non-invasive modern liquid biopsy can detect many cancers at an early stage through the blood. Previously, we believed that multi-cancer screening should focus on limited cancer types, such as pancreatic cancer, which are difficult to detect at an early stage. However, with the accumulation of clinical evidence, these tests can be extended to more cancer types.



Reduce cancer mortality

Don’t forget that cancer is a progressive disease. All solid tumors are benign tumor-like hyperplasias at the beginning, and progress toward incurable metastasis at different rates. After adjusting for the incidence of different cancers, the weighted average five-year mortality rate for local cancers is only 11%, while the mortality rate for distant cancers is 76%, as shown below. In other words, 89% of patients with localized cancer survive 5 years after diagnosis, which is much higher than the survival rate of 24% of patients with metastatic cancer.

The age of genomics in cancer screening: Enabling earlier cancer detection

Source: ARK Investment Management LLC, 2020


In our view, multi-cancer screening can reduce mortality by shifting the average diagnosis from distantly metastatic cancer to localized cancer. After the following analysis, we came to this conclusion. First, we select solid tumor types that are known to produce detectable amounts of free DNA (ctDNA) and/or tumor types that have been included in multi-cancer liquid biopsy screening studies. Our model combines age and tumor-specific morbidity as well as stage-specific morbidity and mortality statistics from the Surveillance, Epidemiology, and End Results (SEER) cancer database. Although we expect that as training data increases, the sensitivity and specificity of detection will increase, but the public performance of GRAIL on limited cancers provides the current baseline (sensitivity=0.67; specificity=0.99). Finally, for the list of cancers we chose, we assumed that the frequency of each diagnosis stage was 70% local, 25% regional, and 5% metastatic, as described in the following table.



The age of genomics in cancer screening: Enabling earlier cancer detection
Source: ARK Investment Management LLC, 2020


With this information, we simulated the impact of multi-cancer liquid biopsy screening on cancer-specific mortality. After five years of adopting this program nationwide in the United States, annual screening will detect (a) cancers that are not covered by existing tests in people over the age of 50, and (b) reduce the number of cancer deaths by 56,000 each year. Coupled with the list of cancers covered by existing screening tests, multi-cancer liquid biopsy screening can reduce the number of cancer deaths by 60,000 each year. Finally, including eligible patients over the age of 40, multi-cancer screening can prevent 66,000 cancer deaths each year, as shown below.



Source: ARK Investment Management LLC, 2020


Although our analysis shows that multi-cancer liquid biopsy screening can reduce 66,000 cancer-specific deaths each year, we are also aware of the obstacles to the widespread application of this technology in the short term.

Although some companies in this field can pursue commercialization in the near future, we expect FDA approval or reimbursement until at least 2023. Without these prerequisites, widespread application is impossible.

In addition, the company will need to solve some problems, such as lead time deviation, excessive or unnecessary treatment, and huge cost investment relative to the current standard of care


(source:internet, reference only)

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Important Note: The information provided is for informational purposes only and should not be considered as medical advice.