A ‘new’ blood test that detects cancers that are undetectable
till date in their early stages
In a major advancement in cancer screening, new study has developed a simple blood test to detect eight different cancers in their early stages, five of which do not have a screening program for early detection.
Cancer remains one of the leading causes of death worldwide. It is estimated that the number of global cancer deaths will have risen from 8 million to 13 million by 2030. Early diagnosis of cancer is extremely key to reduce cancer-related deaths because earlier the disease is diagnosed, the chances of a successful treatment become higher. The diagnosis of many cancers is a long and challenging process. When a person is having symptoms which suggest cancer, the doctor examines the personal and medical history and does a physical exam. After this initial assessment, many tests are generally recommended to be done. First, laboratory tests for blood, urine, body fluids etc are done which can help but usually do not diagnose cancer when done standalone. The doctor will generally suggest one or more medical imaging procedures which create pictures of areas inside the body that help the doctor see whether a tumour is present – an ultrasound or a CT scan to begin with.
Additionally, in most cases, doctors will need to do a biopsy to make a diagnosis of cancer – biopsy is a procedure in which the doctor removes a sample of tissue from the body to be examined in the laboratory to see if it is cancer. This tissue material can be removed from the body using a needle or minor surgical procedure or through endoscopy. This is an elaborate and complex diagnosis process, generally done after the patient starts to show off at least one obvious symptom which then compels him or her to visit the doctor. Many adult cancers grow very slowly, sometimes taking 20 to 30 years to progress to full-blown cancers. Thus, by the time they are diagnosed these cancers have often spread, making them incredibly difficult to treat. Since for many cancers, it is too late when the first symptom appears, this is a major concern for future of cancer diagnostics because earlier the information is available, more likely can the cancer treatment be successful. Unfortunately, many cancers are not caught until the later stages and this is attributed to lack of fast and effective diagnostic tools.
How does this new, innovative cancer screening blood test work?
In a recent study published in Science, researchers have developed a new blood test, which can offer a more simplified yet effective diagnostic technique for many cancers1. The test called as ‘CancerSEEK’, is a novel, non-invasive method to simultaneously detect eight cancer types from only one blood sample. This study carried out by a team at Johns Hopkins University School of Medicine, USA, has demonstrated high specificity and sensitivity for cancer detection among more than 1000 people with cancer and is being touted as a quick and simple way to detect cancer in its early stages and also pinpoint its location.
The study of CancerSEEK has been concluded on 1,005 individuals diagnosed with non-metastatic forms of one of the eight cancers (breast, lung, colorectal, ovarian, liver, stomach, pancreatic, and esophageal stages I to III), for five of which no routine early screening tests are available for people at average risk (those being ovarian, liver, stomach, pancreatic and esophageal). It is very simplistic how this blood tests works to identify the cancer. When cancerous tumours form inside the body after the onset of the disease, these tumour cells release small fragments of mutated DNA and abnormal proteins which circulate into the bloodstream and can act as highly specific markers for cancer. These minute amounts of mutated DNA and abnormal proteins circulate in the blood long before causing any symptoms and are very unique compared to the DNA and proteins found in normal cells. Thus, this blood test works by identifying the markers for 16 gene mutations and eight common cancer proteins (shortlisted after initially exploring several hundred genes and 40 protein markers) that are associated with eight different cancer types indicating the presence of cancer. The small yet robust mutation panel could detect at least one mutation in the different cancers. This identification of cancer markers is a unique classification method because it combines the probability of observing various DNA mutations together with the levels of several proteins in order to take a final diagnosis decision. This method is based on the same rationale for using combinations of drugs to treat cancers. It is important to note that this molecular test is aimed at screening for cancer and is very different from other molecular tests which analyse large numbers of cancer-driving genes to identify targets which can be used to develop therapeutics.
Potential of the test to be impactful for patients
The test yielded an overall result of more than 99 percent and the test was able to identify 70 percent of the cancers with overall sensitivity ranging from lowest 33 (for breast cancer) to an impressive 98 percent (for ovarian cancer). The sensitivity for the five cancers for which no screening tests are available (pancreas, ovary, liver, stomach and esophageal) ranged from 69 to 98 percent. Interestingly, the test was also able to pinpoint the location of tumours in 83 percent of the patients. These results are termed as very ‘encouraging’ and points towards the possibility of having CancerSEEK as a routine screening test for cancer since it has a potential to substantially impact patients to improve outcomes. The overall specificity of the test was also high and this is extremely crucial for avoiding over diagnosis and unnecessary invasive follow-up tests and procedures to confirm the presence of cancer. This specificity was mainly achieved by keeping the mutation panel small. This test was performed on 812 healthy participants and only seven were flagged positive by CancerSEEK, and these patients could be either false positives or even might have early-stage cancer with no symptoms.
Comparing CancerSEEK with other early detection tests
Blood sample have been used for cancer detection, in what is called ‘liquid biopsies’ (compared to normal biopsy in which a sample tissue is removed from the body and is more invasive). These procedures generally survey a large number of genes in an attempt to identify therapeutic targets for drugs. In comparison, CancerSEEK follows an entirely different approach of focusing on early diagnosis of cancer by looking at mutations in just 16 cancer-associated genes and the levels of eight protein as cancer biomarkers. The results from these two parameters could be combined with an algorithm to “score” each blood test which can further ensure the accuracy and reliability of the results. Unfortunately, blood-based “liquid biopsy” tests have been recently tagged as controversial in accurately detect cancer mutations, with their failure in indicating the location of the tumours. Also, they are very expensive – upto several-thousand-dollar – and their ability to become routine tools for diagnosing and guiding treatment for cancer patients is becoming questionable. Remarkably, in this study, in 63% of patients, CancerSEEK specified the organs giving information on how to pinpoint the location of the tumour and in 83% patients, this test pointed two autonomical locations.
Many effective early-cancer detection tests do exist for some cancer types, example mammography for breast cancer and cervical pap smears for cervical cancer. The only widely-used blood-based test is for prostate cancer which looks at just a single protein biomarker, prostate specific antigen (PSA). Though this test has been around for more than three decades, this blood-based test is still not being tagged as useful and necessary.However, some proven screening tests that lead to earlier diagnosis, such as colonoscopy screening for bowel cancer, have associated risks and only screen for one cancer at a time. Also, other blood-based tests for cancer diagnosis like GRAIL2, which has a very strong backing for clinical trials, only tests for tumour DNA, not the additional protein biomarkers which CancerSEEK now includes. Thus, it should be clear in the future which of these two technologies have better vital elements like ability to detect different cancer types and avoiding false-positives. Also, most screenings for specific cancer types are only recommended for people who might be or are expected to at risk owing to their family history of cancer or just older age). Thus, CancerSEEK could be a mainstream for even healthy patients with no signs.
It is non-debatable that early diagnosis is most critical to avoid the potentially devastating impact of many cancer treatments and cancer deaths. Despite the gains made in cancer treatment, advanced cancer care still bears a lot of physical, mental and financial bearings. The cancers which are still localised to their tissue of origin and have not spread beyond can often be cured by surgery alone, thus sparing a patient from the considerable side effects of chemotherapy and radiotherapy treatments.
Researchers hope that CancerSEEK can in the future offer a simple, non-invasive and fast strategy for diagnosing cancer in its early stages. The authors point out that they have adopted a realistic approach during this study and understand that no single test will be able to detect all cancers and although the current test does not pick up every cancer, it does successfully identify many cancers that would otherwise likely go undetected. Also, the proposed cost of CancerSEEK is about $500 and this is far more economical that most currently available screens for just a single cancer types thus can be highly prospecting. The ultimate vision provided by the authors is to have this test being incorporated in routine check-up (preventive or otherwise) in primary health care setting itself, something similar to let’s say a cholesterol check. However, it might take some years for this test to be available in clinic.
To establish this test further, it is necessary to demonstrate how this test can be effective in saving lives one day and so large trials are now underway in the USA for which the results will be available in the next three to five years. Thus, as exciting as this study maybe, oncologists worldwide are waiting for the ongoing large-scale trials to be completed. However, there is no doubt that this unique test has paved the path to shift the focus in cancer research from late-stage cancer to early disease which will be critical in reducing cancer deaths in the long term.
1. Cohen et al., 2018, ‘Detection and localization of surgically resectable cancers with a multi-analyte blood test’, Science, eaar3247, DOI: 10.1126/science.aar3247
2. Aravanis et al., 2017, ‘Next-Generation Sequencing of Circulating Tumor DNA for Early Cancer Detection’, Cell, vol.168, no. 4, pp.571–574. DOI: 10.1016/j.cell.2017.01.030