Contributed Commentary from Dave Mullarkey, ClearNote Health
May 2, 2025 | One of the most important tools we have to reduce mortality from cancer is early detection. Mammograms have had a significant impact in improving outcomes for patients with breast cancer, and colonoscopies have done the same for patients with colorectal cancer. But despite broad recognition of the importance of early cancer detection, our ability to screen for a wide range of cancers is quite limited. In fact, there are only five cancers for which Medicare is directed to pay for screening: breast, cervical, colon, lung, and prostate.
We need a better approach. While many of us are championing the long-term goal of tests that could detect multiple types of cancer from a single sample, it’s important to recognize that the healthcare system is in the early days of trying to get ready to implement this kind of test in routine patient care. Instead, we should focus on a series of strategic, smaller changes that will improve cancer outcomes now and pave the way for multi-cancer testing in the future.
The first in a series of stepping-stones is broadening access to single-cancer tests based on the same detection technologies used for the multi-cancer tests that are currently in development. We should focus on detecting the highest-mortality cancers for which there are no effective early detection tools, and offer tests to patients who are most susceptible to those cancers. This incremental approach is a better fit for today’s regulatory and reimbursement landscape and focuses on areas of the highest unmet clinical need (e.g. pancreatic cancer). It will also give diagnostic developers the opportunity to carefully hone algorithms to deliver exceptional sensitivity for individual cancers at the earliest stages, leverage different AI technologies, and explore the use of multiple orthogonal inputs — such as combining insights from direct changes to the genetic code,, epigenetics, immune system response and glycoproteomics—for optimal results.
Just as important, this shift toward a new generation of highly accurate tests for individual high mortality cancer types should help to broaden adoption and build momentum for behavioral change in patients, physicians, and the broader healthcare system. This will be essential for shifting to an early-detection mindset for even more cancers.
The next stepping-stone will likely involve targeted multi-cancer tests for groups of patients at elevated risk. I could imagine a test built specifically to focus on detecting the most common cancers among long-term smokers, for example, or the cancers most likely to manifest in a patient diagnosed with certain genetic syndromes such as Lynch syndrome. Alternatively, cancers could be grouped based on the purview of an ordering physician — all cancers that would be more familiar to an OB/GYN, for instance, or all cancers typically seen by a gastroenterologist. This might fit more neatly into our healthcare system, avoiding the potential disruption of detecting a cancer with which the ordering physician has limited day-to-day experience.
As we are able to demonstrate success along the way, we’ll be in a better position to usher in an era of multi-cancer tests for early detection of a wide range of cancers in more people. Even now, there are a number of things we can do to prepare for that goal. One excellent example is the National Cancer Institute’s Vanguard Study, which aims to assess the implications of using multi-cancer detection tests. That study recently hit a major milestone when it completed a technology benchmarking assessment and selected two multi-cancer tests to move forward into a study that is expected to enroll as many as 24,000 participants. Results from this study should help us understand how best to roll out multi-cancer detection tests in the future, including issues such as how doctors and patients respond to results and whether those results lead to change in patient care and outcomes.
The stepping-stone approach will also help us improve our models for detecting many types of cancer at once. There’s a lot of variety today in the biological signals that are used to detect the presence of cancer: epigenomic, genomic, proteomic, and other biomarkers are common. We’ll need to find the correct combination of biomarkers for optimal results in each type of cancer. We also have to choose the best content for each test, including how many and which cancers to interrogate. We should plan and design studies today to help us make these decisions in the future. Honing clinical parameters — including specificity and sensitivity for early-stage cancers — will help to reduce the rates of false positives and false negatives, critical factors for tests that are intended for mainstream use. Another key element will be the ability to identify tissue of tumor origin. Without this, positive results call for full-body imaging and potentially a host of other costly follow-up tests. As we improve across all of these dimensions, the outlook for positive reimbursement coverage decisions will increase significantly.
Ultimately, the long-term vision is to get to early detection of multiple cancers with a single test. But we’ll need to embrace incremental change to get there. When we do finally achieve this vision, physicians and patients alike will be empowered not only with the right early detection tools but also with the mindset that this approach will give them the best chance at having long, healthy lives.
Dave Mullarkey is the CEO of ClearNote Health, a company developing blood tests for detection of some of the deadliest types of cancer. He can be reached at dmullarkey@clearnotehealth.com.