- People and doctors often miss early warning signs of cancer
- Nearly 50% of all cancers are diagnosed late when they have already spread
- Each year cancer kills 8m people worldwide and cost billions
- 40% of cancer deaths could be prevented by early detection
- Traditional tissue biopsies used to diagnose cancer are invasive, slow, costly and often yield insufficient tissue
- New non-invasive tests are being devised to detect cancer early
- Such tests are positioned to significantly reduce the vast and growing global burden of cancer
- But before these tests enter clinics, they need to overcome a number of challenges
A paradigm shift in cancer diagnosis
How close are we to developing a simple, cheap, rapid and exquisitely sensitive non-invasive test to diagnose cancer in healthy-looking people?
Recently, attention has been drawn to a breathalyser test for cancer diagnosis, which is just starting a significant 2-year clinical study in the UK. In 2018, a “liquid biopsy” was popularly heralded as “the holy grail” of cancer diagnosis, only quickly to be quashed by medical experts who warned that this conclusion was “premature” and “misleading”. Further, image recognition is increasingly being used as a technique to detect cancer. Given the extent and depth of these endeavours it seems reasonable to assume that, within the next decade, gold-standard solid tumour biopsies for detecting cancer will be replaced by non-invasive diagnostic techniques.
In this Commentary
In this Commentary we describe evolving innovative techniques to detect cancer early, which include a breathalyser, a liquid biopsy and an image recognition test. But first we: (i) briefly describe the epidemiology of cancer, (ii) explain the extent, implications and some of the causes of late diagnosis, which is driving the development of these new non-invasive detection techniques, (iii) describe how ‘personalized’ medicine, predicated upon the molecular signatures of cancer tumours, has become routine clinical practice and demand more efficacious techniques to understand the complexities of cancer.
Cancer is among the leading causes of death worldwide. In 2012, there were 14.1m new cases and 8.2m cancer-related deaths worldwide. 57% of these new cancer cases occurred in less developed regions of the world, which include Central America, parts of Africa and Asia. 65% of cancer deaths occurred in these regions. The number of new cancer cases per year is expected to rise to 23.6m by 2030. It is estimated that over 40% of cancer cases are preventable. In the UK there are more than 360,000 new cancer cases and over 166,000 cancer deaths every year. Since the early 1990s, incidence rates for all cancers combined in England have increased by 13% each year. Annual NHS costs for cancer services are over £5bn, but the cost to British society - including costs for loss of productivity - is over £18bn. In the US, over 1.7m new cases of cancer were diagnosed in 2018 and some 0.61m people died from the disease. It is estimated that in the US the annual national expenditure on cancer is some US$150bn. Early diagnosis and cancer prevention would significantly reduce cancer morbidity and mortality and achieve large cost savings for healthcare systems.
The challenge of late cancer diagnoses
The significance of developing a simple non-invasive test to diagnose cancer early cannot be over-emphasised. For a number of reasons, almost half of people who get cancer are diagnosed late, which makes treatment less likely to succeed, reduces chances of survival and significantly increases the cost of care. For instance, in the UK about 25% of all cancer cases only are diagnosed following presentation in A&E. The vast majority of these cases are already at a late stage, when treatment options are limited, and survival is poorer. Further, a substantial percentage of people neither avail themselves of cancer screening nor present themselves to primary care physicians with early symptoms. A good example of this is cervical cancer screening in the UK, which is offered every three years to all women aged between 25 and 64. Despite the test only taking a few minutes, each year over 1.3m women choose not to attend, and non-attendance is the biggest risk factor to developing cervical cancer. Each year, some 220,000 women in the UK are diagnosed with cervical abnormalities and over 800 women die from the disease.
Implications of inefficient healthcare systems
Late diagnosis not only occurs for non-compliance. Some cancers are asymptomatic while others have general non-specific symptoms and are often mistaken for lesser ailments. Further, inefficiencies in healthcare systems can lead to late diagnosis and increased cancer morbidity and mortality. For example, in February 2019 the UK’s National Audit Office (NAO) published an “Investigation into the management of health screening”, which concluded that none of the key screening programs in England - for bowel, breast or cervical cancer - met their targets because of management and IT failures. As a consequence, about 3m women across England have not had a cervical cancer test for at least three-and-a-half years. In 2018, more than 150,000 cervical screening samples piled-up in laboratories due to outdated IT systems, staff shortages and changes in testing procedures. Faulty IT systems also are reported to have resulted in 5,000 women not being invited for breast screening, which in England is currently offered once every three years to women aged 50 to 70. According to the NAO report, in 2017 450,000 women missed a final breast cancer screening test because of a system failure, which is believed to have been responsible for some 270 deaths.
Molecular biology challenges to gold standard solid tissue biopsies
In the past decade, ‘personalized’ medicine predicated upon the molecular signatures of cancer tumours has become routine clinical practice. The identification on tumour tissue of predictive biomarkers of response to personalized targeted therapies is now considered optimal patient care. Notwithstanding, such treatment faces a number of biological and technological challenges associated with traditional solid tumour biopsies' access to tumours and the heterogeneity of tumours.
While some cancer tumours are easily accessed, others have limited accessibility because they are either deep in the body or embedded in critical organs. This makes obtaining a comprehensive “picture” of such tumours challenging and may increase clinical complications. Further, tissue samples from different regions of the same tumour may differ and tissue specimens from primary and metastasized tumours can also differ. In addition, studies have shown the dynamic changes of tumour features over time and the emergence of therapy-resistance. Thus, inter- and intra-tumour heterogeneity pose a pivotal challenge to guide clinical decision-making in cancer therapy as traditional biopsies may be unable to capture a complete genomic landscape of a patient’s tumour.
A non-invasive test, such as sampling blood, urine, salvia and breath can provide the same genetic information as a solid tissue biopsy and has certain added advantages, which include: (i) they are a source of fresh tumour-derived material, unhampered by preservatives and (ii) they provide an alternative sample type in routine clinical practice when tumour sampling is unavailable, inappropriate or difficult to obtain.