Nickolas Papadopoulos, Ph.D., Professor of Oncology and Pathology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Director of Translational Genetics, Ludwig Center at Johns Hopkins University
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Detecting cancer earlier is only part of the challenge. The next frontier is identifying which precancerous lesions are biologically destined to progress. Papadopoulos points to combinations of DNA, RNA, proteins and other biomarkers, as well as sampling bodily fluids closer to the lesion, as promising ways to find these elusive signals.
One approach is to identify some combination of biomarkers that could increase the sensitivity. There is work being done on this and, in addition to DNA, other biomarkers are being studied, like proteins and RNA.
Another approach is to use a different medium than blood, like bodily fluids that are closer to the source of the lesions desired to be detected. For example, the use of urine for detecting bladder lesions.
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The first randomized MCED trial to report results raised a more fundamental question about how these tests should be judged. Papadopoulos argues that simply counting Stage III and IV cancers misses important differences among tumor types. Future trials will need to show whether screening finds cancers when cure is realistically possible, while also measuring survival, benefits and harms.
What is important is to look at the type of tumors identified and at what stage. For some tumor types Stage III is manageable, while for other tumor types even Stage I is not.
Future randomized controlled prospective interventional studies should focus not only on the reduction of stage. For example, the endpoints should include a more detailed view that includes the cancer types detected, the stages identified, in how many cases there is an opportunity to treat people with intent to cure, and cancer-specific survival, to mention a few.
We need to know the benefits as well as the harms of MCED tests before widespread adoption.
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For population screening, false positives can quickly overwhelm the benefits of a test because cancer remains uncommon among asymptomatic people. Papadopoulos says the strongest case for MCED will come from finding cancers that currently lack standard screening tests, before symptoms appear and while treatment still has curative potential.
What will keep me going is detection of cancers for which we do not have standard-of-care tests, detected before symptoms at stages where there is an opportunity to manage these individuals with intent to cure.
I see early detection of cancer as being proactive, instead of reactive, about detecting the disease to address underdiagnosis. Earlier detection of cancer will result in the reduction of sickness and death from cancer. It provides an opportunity to deliver management, including surgeries and therapies, with intent to cure and not just to prolong life. Drugs that are now used to treat metastatic stages of cancer should have better results in individuals whose cancer was detected earlier.
I do not mean to minimize other aspects associated with the successful clinical implementation of a test, like cost, accessibility, etc. I have focused my answer on why it is worth trying to deliver such a test.
