The story that Deborah from Monroe, Georgia tells of her experience with colorectal cancer is one that will resonate with anyone that has gone through a similar journey. In the two weeks leading up to her fortieth birthday, she experienced severe diarrhoea and eventually rectal bleeding, which led her to see her physician1. One colonoscopy and an agonising two week wait later, Deborah was delivered the life-shattering news that she had been diagnosed with Stage III colorectal cancer. The facts of Deborah’s situation were stark – the survival rate of indivudals diagnosed with this stage of colorectal cancer can be as low 58%2. While her cancer had not yet spread to other tissues, it had colonised through many layers of her bowel had invaded nearby lymph nodes, the structures that cancer cells use to escape their tissue of origin and spread to other parts of the body – a process known as metastasis.
Thankfully, Deborah survived her battle with cancer – she was in the lucky 58%. She is also a living proof of the importance of early diagnosis. Currently, only people aged 50 or over are required to have a colonoscopy – the main diagnostic tool for detecting colorectal cancer – in the United States.
For many cancer sufferers, theirs is an ‘if-only’ story.
Deborah was 10 years short of this mark and already presented with stage III cancer. Had she waited longer, it is possible that her cancer would have metastasised and she would have progressed to stage IV, where treatment options are limited – and those that are treated have to deal with the most aggressive and unpleasant methods – and survival rates plummet to 11%2.
Deborah’s story is one of the positive ones. For many cancer sufferers, theirs is an ‘if-only’ story. If only they had come to their doctor earlier. If only their diagnostic tests had been scheduled sooner. If only they had longer with their loved ones.
As the complex causative factors underlying cancer development become better understood, it is clear that cancer prevention and early intervention – when the cancer is still relatively confined and easy to treat – are key. Currently, each type of cancer has its own diagnostic method. Colorectal cancer is diagnosed by a colonoscopy, oesophageal cancer by endoscopy and so on. These methods, while well-established and diagnostically useful, are not without their faults – they are relatively expensive to carry out, their results are subject to the opinions of the physicians interpreting them and often patients’ cancers must have progressed to a point where they are experiencing symptoms, which may be too late for some. The holy grail of cancer diagnosis, a method that not only avoids these problems but is also able to diagnose a number of cancers, has so far eluded researchers. However, this may be about to change.
A group consisting of over 40 researchers dotted across the globe last month presented an exciting diagnostic tool that could be this missing weapon in doctors’ arsenals. Their tool is able to detect 8 common cancers, not only signalling that the patient may have a form of cancer but also giving an indication of which tissue the cancer originated from3.
The findings are exciting for a number of reasons. Firstly, it would be the first broad-range, blood-based cancer detection procedure, reducing the need for expensive and invasive procedures such as colonoscopy or biopsy. Secondly, their tool, which the researchers call CancerSEEK, is able to improve levels of specificity to successes never previously reached. Most soft-tissue cancers, while seeking to live a clandesdine life, release indicators of their presence in the form of circulating tumour DNA (ctDNA). These are short lengths of DNA released when cancer cells die that can survive for a short time in the blood and plasma. These ctDNA strands, if detected, can be analysed and the underlying mutations that caused the cancer laid bare. CancerSEEK is designed to detect the most common driver mutations of the eight cancers in question with remarkable specificity – researchers discovered that by splitting patient samples into many different vessels and testing each of these improved their chances of finding the DNA strands they were interested in. Phrasing it in terms of the inevitable needle-in-the-haystack metaphor, splitting samples into different vessels and analysing each of these essentially means looking for the same size needle in many, smaller haystacks – if it is there, you will be more likely to find it.
CancerSEEK is also unique in that it combines its search for these floating mutant DNA strands with a search for other indicators that a cancer may be present – heightened levels of biological molecules called biomarkers. The combination of a search for 61 common mutations and 8 protein biomarkers yielded a tool that was able to accurately detect cancer in 70% of known sufferers. Importantly, only 0.009% of individuals were registered as a false positive, showing the test to be both sensitive and accurate – any diagnostic tool must have both of these properties to be viable.
In a yet more exciting finding, researchers were able to use the exact sequence of the ctDNA detected by CancerSEEK to identify which cancer the people in the trial were suffering from. Encouragingly, CancerSEEK was able to indentify some forms, such as ovarian and liver cancer, with nearly 100% accuracy. The early classification of cancer is crucial, as people can begin to undergo the correct programme of specific treatment as soon as possible.
While potentially transformative, it is important to acknowledge that there is some way to go before the technology is widely used. Firstly, the test was most able to detect cancers in those with stage II or stage III disease, when the cancer is already well established and harder to treat. For CancerSEEK – or a similar technology – to be a useful diagnostic tool, it must be able to accurately detect cancers as early as possible, as treatment is most successful when cancers are caught at their earliest stages.
Second, the technology must be put under more substantial interrogation. In this trial, participants were either completely healthy or had a confirmed cancer diagnosis. In reality, patients may display an array of symptoms and markers that could easily be a sign of cancer – such as chronic inflammation – but may not have the disease. It will be important to identify these potential false positives to avoid unnecessarily putting people down the tough road of chemotherapy. Finally, as is the case with all small-scale proof-of-concept studies, the next stage of testing will be trials of larger populations, displaying a wider range of cancers.
The eight common cancers included in this study contributed to 83,000 deaths in England and Wales in 20164 and 360,000 deaths in the United States in 20175, 56% and 60% of the deaths caused by cancer respectively in those regions that year. For each, the impact of early intervention is substantial – on average, the likelihood of patients surviving their cancer drops by 35% when comparing diagnosis at Stage III with Stage I (see Figure 1)2,6,7,8,9,10. Alongside more effective and less unpleasant treatment, the development of diagnostic tools such as CancerSEEK will surely be a crucial weapon in the battle to substantially reduce cancer deaths across the world.
