In this second interview of a 4-part series, Dr. Achim Regenauer answers questions relevant to Life & Health underwriters on advances in cancer diagnostics.
Cancer is a major primary cause of death, ranking in first or second place for middle and older age groups, making this an extremely important focus area for healthcare and the life insurance industry. The goal of cancer screening is to cure cancer by detecting the cancer at its earliest, and still curable, stage, prior to the onset of first symptoms. The most commonly available screening investigations recommended to the general population depending on age, are mammographies for breast cancer, cervical cytology (PAP tests) and human papillomavirus testing for cervical cancer, colonoscopies for bowel cancer and CT scanning for lung cancer. Other screening investigations, such as prostate specific antigen (PSA) tests, ultrasound and MRI for prostate cancer, remain controversial in view of the lower benefits of early detection. So, we are talking about screening for just five common cancers. Considering there are over 200 known cancer types, this is very few. It’s also worth noting that the more unpleasant the examinations are, the fewer individuals take them. For example, according to the American Cancer Society, in the past three years around 81% of women aged 21 to 65 had a PAP test, whereas in the last 10 years only 60% of men aged 50 to 75 had a colonoscopy.1
Certainly. Liquid biopsy in theory avoids some of the key limitations of conventional tumor tissue biopsies. For example, conventional biopsy involves painful, invasive access to the tumor via a thick needle, which can be more like a minor surgery including a complex surgical preparation. Furthermore, in some cancer sites, such as the liver or pancreas, conventional biopsy is often difficult. In other sites, such as the brain, it’s rarely feasible. In contrast, liquid biopsy involves a simple, painless blood draw, which can be performed time and again, making it ideal for annual screening. Another major difference to note is that liquid biopsy does not, as with a conventional biopsy, target one cancer site only, but rather provides the molecular profile of a hidden cancer in any site, which the test also identifies. With this, the odds of detecting a cancer at an early stage are much higher than with a conventional biopsy, and this is indeed very good news for oncology, as catching a cancer early can substantially improve the chance of successfully treating that cancer.
Before I answer that let me just clarify that this is not just about screening. As often happens with medical advances, media hype has led to some misconceptions about liquid biopsy, including that liquid biopsy can only be utilized for cancer screening. The fact is that liquid biopsy is an advance in cancer diagnostics that can be utilized along the entire lifecycle stages of a cancer, i.e., for screening, confirmation of a suspicious finding from imaging (diagnosis), staging, testing responsiveness to treatment, minimal residual disease detection and ongoing surveillance after treatment. In our industry, we often focus this term far too narrowly on screening only.
As regards the extent to which liquid biopsy is being applied now in the clinical setting – for screening and testing throughout all cancer lifecycle stages – the answer is that current routine applications of liquid biopsy in medicine are still low-key. The first cancer type benefitting from liquid biopsy is non-small cell lung cancer (NSCLC), for which liquid biopsy testing is in use in some areas for minimal residual disease detection and ongoing surveillance.2 Other cancer types, such as breast, ovarian and prostate, may follow soon. Initial clinical applications of liquid biopsies are likely to begin with later lifecycle stages of cancers, i.e., for minimal residual disease detection or as a companion test for an immunotherapy treatment, such as amivantamab therapy for patients with EGFR-mutant NSCLC.
Yes and No. Multicancer screening tests would indeed be the cherry on the liquid biopsy cake. Until recently, achieving such an ambitious goal seemed far off, because cancers are such a highly heterogeneous group on many levels (e.g., histology and genes). However, an impressive, independent validation study has now been published.3 This study gives reason to assume that a large-scale multicancer screening test clinical application is indeed conceivable in the medium-term future. So, ‘yes’, a sea change is potentially close. However, ‘no’ and ‘soon’ are also possible answers. To give a few more insights. The Galleri test is designed to detect more than 50 types of cancer through a single blood draw, out of which 45 cancers don’t currently have another recommended screening. The performance of this screening test was quite high with an overall specificity of over 99% and a sensitivity across all stages of 51.5%. Currently, a larger clinical development program is underway to collect additional data from the test in large, prospective studies in the US and UK, with the objective of examining its feasibility for screening populations. The Galleri test is also one of three multicancer screening tests under investigation, the other two being the CancerSEEK assay and the PanSeer assay.
It seems that the development of multicancer screening tests is progressing faster than previously assumed, but many challenges must still be overcome, i.e., validation and clinical utility. This could take years, even a decade. Promisingly, two major national healthcare systems, the US and the UK, are already including possible applications of these tests in their future planning. In the US, the Galleri test has not yet been approved by the US Food and Drug Administration, but it is already commercially available (from a healthcare organization for an out-of-pocket cost of around USD 950)4, with test results available within weeks. The company behind the Galleri test, GRAIL, is striving for an FDA approval in 2023.
NSCLC cancer has already indicated that all cancer lifecycle stages will benefit from liquid biopsy, though likely starting with later stages, so we can expect a significant impact on cancer care. As to screening, even if multicancer screening tests prove to be efficient and useful, it is likely that where recommended screening options already exist, multicancer tests will be complementary to these, rather than a substitute for them.
In the medium term, the likely implications for Life and Health insurance, as for healthcare systems, are huge. It is certainly time for the insurance industry to monitor these advances in view of the potential impact on products, pricing, claims and underwriting approaches. For underwriting, this would mean an increased number of diagnosed cancers, a shift in detection to earlier and more treatable stages, leading to lower mortality, and also a potential increase in adverse selection.
View the first interview in this series, on general cancer trends.
1 Cancer Prevention & Early Detection, Facts & Figures 2019-2020. American Cancer Society. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/cancer-prevention-and-early-detection-facts-and-figures/cancer-prevention-and-early-detection-facts-and-figures-2019-2020.pdf
2 Guibert, N. et al.; Current and future applications of liquid biopsy in nonsmall cell lung cancer from early to advanced stages. DOI: 10.1183/16000617.0052-2019 https://err.ersjournals.com/content/29/155/190052
3 E. A. Klein et al.; Annals of Oncology; Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set https://www.annalsofoncology.org/article/S0923-7534(21)02046-9/fulltext
4 Roxanne Nelson; Medscape May 17, 2021; Blood Test for 50 Cancers Coming to US Clinics Soon; https://www.medscape.com/viewarticle/951268