By Dr. Eddie Chaloner - Consultant Vascular Surgeon
Most people are frightened of cancer. That’s fair enough – because about 40% of people will suffer from cancer in their lifetimes and a substantial number will die from it. During my working lifetime, there have been ma
ny advances in cancer medicine. One of the most notable has been the proliferation of screening programmes - it’s possible this area is about to undergo a major change.
Most people know that picking up cancer at an early stage is highly beneficial. Survival outcomes are far better if the disease is promptly diagnosed and treated rather than picked up late when it has spread. If patients are referred only when symptoms are noticed, such as a lump, or abnormal bleeding or unexplained weight loss, we may have missed the boat to cure the cancer.
This has been the rationale behind screening – to detect disease before physical symptoms become apparent and treat the problem at an early stage. Common cancers such as breast, cervical and bowel cancer have population wide NHS screening in the UK and the private sector offers many more screening options.
Screening itself is not without controversy. Although to the layperson, it might be thought an obvious benefit, there are several potential downsides. Some cancers are picked up which might never cause clinical harm because they are so slow growing. All screening programmes pick up false positives which then require extensive investigation and generate substantial anxiety. There is also the problem of lead time bias – simply put, the patient appears to live longer because the cancer was detected earlier, but, had the cancer not been detected on screening but picked up clinically a few years later, the outcome would have been the same. The screening appears to have provided a longevity benefit - in fact this can be a statistical illusion.
Most cancers are detected by some form of medical imaging such as ultrasound or CT scanning, or by an investigative procedure such as sigmoidoscopy or colonoscopy for bowel and cervical cancer. These tests are time consuming, expensive and carry small degrees of risk. The emerging trend is to augment these techniques with biochemical analysis of blood or other body fluid – the so called ‘liquid biopsy’.
Advances in technology for detecting and analysing genetic material have opened up this new frontier of medical diagnostics. Most liquid biopsy techniques rely on finding and analysing bits of free cancer cell DNA floating around in the blood, or even whole cancer cells shed from the main tumour. Some techniques are already used in monitoring response to treatment in certain cancers (particularly lung cancer). By amplifying bits of tumour DNA shed into the bloodstream from a known cancer, if the disease is mutating to evade a particular type of drug, this can be detected at an early stage and medication adjusted accordingly.
The area where liquid biopsy generates most excitement is in the possible application for mass screening of the healthy population. It sounds great! Rather than undergoing scans involving ionising radiation or unpleasant invasive tests like a colonoscopy, everyone could just drop in for a quick blood sample once a year. Only people having an abnormality on the blood test would then need to have imaging tests, so that might save a lot of time and money.
Unfortunately, it is not quite that simple.
Amplifying bits of tumour DNA might suggest that the person has a cancer, but does not necessarily define what organ the cancer is in – so the patient still needs extensive investigation. There are concerns that fragments of DNA ostensibly from a tumour, may in fact be from cancers that would be knocked out by the normal functioning of the immune system and not progress to cause significant disease. Large scale trials are currently underway (such as the Gallieri trial in the UK) to shed light on these questions.
Other interesting types of screening include analysis of metabolic chemicals which change when a person has an undiagnosed cancer – so called quantitative metabolomics. Some cancers produce specific and identifiable molecules as a consequence of disordered metabolism and these can be detected not just in blood, but in urine, sweat and exhaled breath. Once again, more work needs to be done to establish the applicability of these tests as mass population screening techniques.
In the final analysis, the driver behind development of liquid biopsy utilisation as a screening tool will be money.
It is no coincidence that one of the leading players in this area is a company called Grail – ‘a thing which is eagerly pursued or sought after’. As we know more about cancer and the cellular changes that create and grow tumours, the opportunity for earlier diagnosis and bespoke individualised treatment is enticing.
Published by By Dr. Eddie Chaloner, Consultant Vascular SurgeonMA(Oxon) BM BCh FRCS(Edin) FRCS (Gen)About Dr Loxley @drloxleycare www.drloxley.com
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