Cancer is one of the leading causes of death globally, accounting for approximately 8.8 million (or one in six) deaths in 2015. New cancer cases are expected to increase by approximately 70% over the next two decades.
Cancer also has massive global financial implications. The total impact of premature death and disability due to cancer in 2008 (the latest year for which figures are available) was USD 895 billion, representing 1.5% of the world’s gross domestic product (GDP) that year. Its burden on health and finances can be reduced through early detection and effective management, as there is a higher probability of cure if the disease is diagnosed at an early stage.
Researchers have long been exploring alternate ways to screen for and diagnose cancer. One option gaining ground in recent years is liquid biopsy; i.e., the testing of blood or other bodily fluids for specific cellular biomarkers.
This is not a new concept. Circulating protein tumor markers such as carcinoembryonic antigen (CEA) or prostate-specific antigen (PSA) have been used for years to screen for cancers. These tests, however, have had limited use, as many cancers do not have a reliable protein biomarker, and even for those that do, the proteins could be elevated due to reasons unrelated to tumor growth.
Also, traditional diagnostic techniques such as tissue biopsy or imaging studies are usually not used for screening purposes; rather, they are recommended only if the patient shows symptoms or a suspicious lump, at which point the disease might already be well-established.
Recent advances are making it possible to test blood or other bodily fluids for biomarkers that identify cancer in patients, such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). As liquid biopsies are gaining a foothold in clinical practice, insurance professionals must understand them and their uses.
About liquid biopsies
A liquid biopsy is a test that detects the presence of tumor products circulating in bodily fluids (e.g., blood, urine, saliva, cerebrospinal fluid, etc.). These tumor products can include:
- Circulating tumor cells (CTCs): Cancer cells which have been shed from a tumor and are present in bodily fluids.
- Circulating tumor DNA (ctDNA): Strands of single- or double-stranded DNA released by cancer tumor cells into the blood.
- Circulating transcriptome: Coding and non-coding RNA molecules in bodily fluids.
- Exosomes: extracellular membrane vesicles.
Early detection of cancer is one of liquid biopsy’s most important potential applications. Since the tests are minimally invasive, they could become routine screening tests, enabling cancer diagnoses at far earlier stages. They could also be useful in assessing and monitoring early-stage cancers where a tissue biopsy might not be possible due to small lesion size or technical difficulty.
Liquid biopsy can also identify tumor-associated mutations from ctDNA, which can help stratify a tumor’s molecular profile and so enable clinicians to optimize patient therapy. The frequency and dynamic alteration of gene mutation in ctDNA correlate with a tumor’s grade and stage, which supports estimates of tumor progression and evolution.
Additionally, liquid biopsy can monitor and predict the effectiveness of treatments and cures as well as the risk of recurrence. Researchers have found, for example, that lung cancer patients with epidermal growth factor receptor (EGFR) C797S mutation in their ctDNA develop resistance to the drug AZD9291, which suggests the diminishing curative effect of this drug and the need to modify the treatment modality. In addition, PIK3CA mutations in ctDNA can detect minimal residual disease (cancer cells from the bone marrow) after chemotherapy or surgery for breast cancer.
As the technology of liquid biopsy develops, testing for ctDNA in particular is likely to find more applicability.
In addition, it is still unproven whether the presence of ctDNA in bodily fluids can provide a full picture of a patient’s cancer; i.e., whether all metastases contribute to ctDNA, CTCs, transcriptome and exosomes, or if all tumor cells release ctDNA into the circulation.
Liquid biopsy is more effective at detecting certain cancers than others. It is, for instance, less effective in detecting brain cancer.
Additionally, the cohort size used in most current liquid biopsy research has been small (range 3-1,000). Findings should be tested in much larger cohorts and over longer time spans to establish liquid biopsy as a reliable means for cancer screening.Read More +