Steven Sorscher
There are over 19 million cancer survivors living in the U.S. After enduring the hardships of definitive therapy to cure their cancer (eg, surgery and adjuvant chemotherapy) cancer survivors commonly ask, “Am I cured?” or “How likely is it that my cancer will relapse?” Following the definitive therapy intended to cure the cancer, circulating tumor DNA (ctDNA) shed from microscopic areas of minimal residual disease (MRD) can be detected in the blood. If MRD is detected, patients have a nearly 100% chance of relapse. Tragically, recurrences are typically incurable. On the other hand, if serial ctDNA blood tests do not detect MRD, the likelihood of future relapse is very low.
Therefore, ctDNA assays can be thought of as crystal balls now available to cancer survivors. After completing definitive therapy, they predict with near certainty whether a patient’s cancer will recur. In fact, in recently reported reviews of dozens of scientific studies, ctDNA assays have been referred to as the “holy grail”, and “revolutionary” and as a “game-changer.” As a result, Medicare now covers the cost of ctDNA testing for patients with several common cancer types.
The results of a ctDNA test can be therapeutic. Two-thirds of cancer survivors suffer from fear of cancer recurrence (FCR) making it the most common long term complication from a cancer diagnosis. Gao et al stated, “Many patients [after definitive therapy] also experience what is, at least in hindsight, needless fear of recurrence … that negatively impacts their quality of life.” The authors suggested that undetected ctDNA results would mitigate FCR in many patients.
Also, patients might find ctDNA results helpful in making decisions about additional therapy intended to improve their likelihood of cure. For example, after surgery, patients diagnosed with breast cancer commonly decline adjuvant chemotherapy and/or adjuvant endocrine therapy, notwithstanding the recommendation from their clinician or tumor board that those treatments represent the best strategy to ensure cure. Although detecting ctDNA after surgery does not indicate a benefit from those adjuvant therapies, it does predict near-certain recurrence if no adjuvant therapies are used. For that reason, without the ctDNA results, a patient might decline the recommended best adjuvant therapy strategy yet choose to accept that very recommended strategy if testing is done and ctDNA is detected.
Currently, only a small proportion of patients are offered ctDNA testing to detect MRD. The National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) publish the standard-of-care guidelines for tests that cancer patients should be offered, but neither endorse ctDNA testing for minimal residual disease detection.
Among their first lessons, medical students are taught to only order a test if the results are “actionable” or have “clinical utility.” The NCCN and ASCO do not endorse ctDNA testing because it lacks clinical utility. A test has clinical utility if there is evidence that the test results can be used to improve outcome for a patient. Put simply, neither the NCCN nor ACSO believe there is evidence that by detecting MRD using ctDNA, a treatment can be initiated which is proven to improve the outlook for the patient.
On the other hand, the prognostic information itself provided by ctDNA assays may be valued, even if having that information does not suggest a treatment that can be applied to improve life expectancy. Recently, Hamaker et al reviewed eighteen studies and reported that surveyed patients found “prognosis and chance of cure” as the highest ranked category of information patients desired, whereas the “treatment options” information category ranked third.
Also, per the United States Secretary’s Advisory Committee on Genetics, Health, and Society: “Clinical utility refers to … the value of information to the person being tested … Even if no interventions are available to treat or prevent disease, there may be benefits associated with knowledge of a result.”
Certainly, some patients will decline ctDNA testing. A patient of mine had completed a hellish experience four years earlier intended to cure her colon cancer which involved surgery followed by 6 months of chemotherapy. She told me that every few weeks she worried about the possibility her cancer would recur. I explained that if ctDNA was now undetectable, the likelihood of recurrence was very low. However, I also told her that if ctDNA was now detectable, eventually her cancer would almost certainly recur. She declined ctDNA testing and quoted the poet Alexander Pope saying, “I guess I prefer having the eternal sunshine of the spotless mind.”
CtDNA tests to identify MRD are now widely available and covered by Medicare and other payers for cancer survivors who have completed definitive therapy for common types of cancer. However, ctDNA assays are not yet recommended in standard of care guidelines. Many patients will decline testing due to the anxiety the results might invoke and the lack of proven clinical utility of ctDNA testing. After all, detecting MRD suggests near-certain eventual recurrence and recurrences are typically incurable. If they are first informed of the profound implications associated with ctDNA results many patients will choose to undergo ctDNA testing. For these patients, ctDNA testing might reasonably be considered as a crystal ball that predicts with remarkable accuracy whether their cancer will recur or is instead cured.
Photo from Flickr user Véronique Debord-Lazaro
Dr. Steven Sorscher is Medical Director, Oncology at Biotheranostics, Inc. He received his undergraduate degree from Yale University, graduated from the University of Michigan Medical School where he also completed his residency in Internal Medicine. He completed his fellowship training in Hematology /Oncology at the University of California, San Diego (UCSD).
Over the past 35 years, Dr. Sorscher has held medical oncology community practice positions at the Gundersen Clinic in LaCrosse, WI and the Marshfield Clinic in Wausau, WI. He also held faculty appointments at UCSD, Duke University in Durham, NC, and Washington University in St. Louis. During the past eight years, Dr. Sorscher was a Professor of Medicine in the Oncology Division at the Wake Forest Medical School, in Winston-Salem, NC, followed by one year as the Medical Director, Oncology at Invitae, Corp. Dr. Sorscher has authored over 140 peer-reviewed publications and four book chapters covering a wide range of topics including breast cancer and hereditary cancer syndromes.
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