Alarming Issues with the Current Oncological Standard of Care

Detecting cancer recurrence as early as possible is integral to preventing disease progression to later and deadlier stages of cancer. However, are we employing tools reliable enough to make this detection, or are the flaws in our current practices being overlooked? Written by Rayna Saldanha, Bryan Kaplan, Claire Liddy, and Kesavan Venkatesh.

It is widely accepted that the fight against cancer is non-linear, with cancer recurrence being a common occurrence even post various cancer therapies. However, the earlier the recurrence can be detected, the higher the patient’s chances of survival. This is because it provides patients with the opportunity to start treatment immediately, inhibiting disease progression. Currently, disease recurrence is monitored and detected using Carcinoembryonic Antigen tests as part of the standard of care in oncology.

The Carcinoembryonic Antigen (or CEA) test is a blood sample test performed by oncologists to monitor cancer growth and manifestation. It is not used for a first-time diagnosis, but rather is conducted post-diagnosis (to obtain a unique base-marker for that patient) and subsequently throughout and post-treatment every 3–5 months for 5 years. Post cancer diagnosis but before treatment, the patient receives a CEA test to provide oncologists with a general benchmark of what this patient’s CEA level gravitates towards when they have cancerous cells. Expectedly, this CEA level falls post initial surgery and treatment. During routine checkups post-treatment, CEA tests are conducted to ensure there is no recurrence, with a spike in CEA toward the base-mark suggesting possible recurrence.

Issues with CEA

In the recent past, diagnostic studies have raised some concerns about the reliability of CEA tests in monitoring disease recurrence. One issue is that CEA tests have a low sensitivity (50–80%), which implies that despite the volume of tests that are currently administered, a patient’s disease recurrence is likely to be caught much later than true onset. The patient’s disease will progress unchecked to later stages of cancer, creating not only higher treatment costs but also potentially fatal conditions for the patient.

Another issue is that CEA tests are generally non-specific: a rise in CEA levels is not necessarily a function of cancer recurrence, as it can also be caused by smoking, bronchitis, and alcoholic cirrhosis among other conditions. Finally, CEA tests are not even treated as a final, definitive cancer indicator; a rise in CEA levels is followed up by more robust imaging (usually CT scans) and endoscopic examinations to confirm cancer recurrence. These make our current dependence on CEA tests — which are statistically faulty and non-definitive in their own right — in standard cancer diagnostics is questionable, administering a glaring need for a more reliable test for cancer recurrence.

Is there a solution?

Oncologists and researchers have developed a promising solution to this problem — replacing CEA tests with ctDNA tests. ctDNA (circulating tumor DNA) is a better indicator of residual disease in the body, with a greater sensitivity than CEA tests (80–90%) that allows them to detect early onset of cancer recurrence. This will accelerate treatment so that fewer patients develop metastatic disease, ultimately decreasing overall morbidity and treatment costs. In addition, the high specificity of ~80% indicates that a positive ctDNA test is conclusive evidence of disease recurrence. Furthermore, when establishing ctDNA as the standard of care there are huge cost implications. Since ctDNA detects positive MRD earlier and more efficiently than other tests, thousands of patients could be saved from the cost of chemotherapy down the line. Thus, saving lives while also saving money. From this, it is apparent that replacing CEA tests with ctDNA would prove greatly beneficial to oncological practices.

Based on current research and technology, it is apparent that many of the big names in the industry have recognized the benefits of replacing CEA with ctDNA testing. Both large biotech firms and newer entrants in the industry such as ArcherDX, Genosity, Inivata, Natera, C2i Genomics, and Adaptive Biotechnologies are developing assays to detect this recurrence, and using ctDNA as their biomarker of choice. Their ongoing clinical trials have displayed the commercial capabilities of ctDNA, and assays are being recognized by practicing oncologists and approved by medicare. While its incorporation into the standard of care may take longer than ideal with clinical trials still underway, it has reached a consensus that CEA testing needs to be replaced in the oncological standard of care in order to take a step closer to saving lives from this disease.