Incidence of colorectal cancer (CRC) since the mid-1980s double in individuals aged 20 to 39 years. As infamous as the disease itself is the treatment patients must endure to get rid of the cancer. Case in point: After undergoing surgery to remove the tumor, high-risk stage II CRC patients and all stage III CRC patients are advised to receive chemotherapy, a treatment regimen that has been used since the 1940s, as well as other treatments such as radiation, surgery to remove possible any residual cancer.
However, despite its widespread use, chemotherapy has several drawbacks – chief among them, it can be debilitating side effect. In addition, patients may face a significant financial burden long after the cancer has been cleared. Finally, receiving chemotherapy may not be worth the side effects or financial cost, as not every patient will benefit from it. For example, in the case of stage III CRC patients involving auto-recommended chemotherapy, up to 40% of patients have been cured by surgery.
More precise tools are needed to assess the need for and response to chemotherapy in CRC patients. Molecular-level assays that have been used in the clinic so far can help provide the clarity needed to better inform these treatment decisions.
Opportunity to improve standards of care
There are two key opportunities for improvement in the way oncologists prescribe chemotherapy regimens for patients with stage II and III CRC. The first is to assign the cancer stage, which is currently determined by the results of a physical exam, imaging tests (X-rays, CT scans, etc.), endoscopy, and any biopsies taken before treatment begins. However, these methods are not sensitive enough to detect residual traces of cancer.
Because cancer staging plays an important role in determining whether a patient needs chemotherapy—as previously noted, high-risk stage II patients and all stage III CRC patients receive chemotherapy—molecular testing tools can provide a more accurate risk of recurrence, should be a key factor in staging decision-making. Without molecular-based testing, CRC patients may undergo post-surgical treatment that may be unnecessary, expensive, and physically exhausting, or, conversely, forgo treatment when the intervention is beneficial to the patient.
The second chance for improvement is during treatment monitoring. After chemotherapy begins, oncologists try to determine whether a patient’s cancer is growing or shrinking. Rather than watching the cancer’s response to chemotherapy in real time, clinicians must wait for the cancer’s response to be detected by established methods such as imaging and microscopy. This can take months, and customizing individualized care is difficult or impossible. Molecular testing could provide an easier way to monitor treatment response in real time and help oncologists stop chemotherapy as soon as the cancer is cleared.
Circulating tumor DNA could lead the way
A promising molecular detection tool that could improve our current treatments for CRC is circulating tumor DNA (ctDNA), which is released into the bloodstream by cancer cells. Because it uses a simple blood draw to measure the total amount of ctDNA in a patient’s blood, the ctDNA liquid biopsy test provides oncologists with an accurate, molecular, real-time tool for cancer detection.
In cancer staging, such a tool would provide clinicians with a more precise way to determine the true stage of a cancer. From then on, they will also be able to better assess how aggressive the treatment options should be. In addition, in treatment monitoring, molecular-level detection methods can help oncologists observe cancer behavior in real time and enable clinicians to stop treatments that are ineffective or the cancer has cleared. In addition, it can help oncologists choose which patients can have their cancer cured with surgery, so chemotherapy is not needed at all.
Current research on ctDNA in CRC
Supporting this claim is growing evidence that ctDNA is a viable addition to oncologists’ current strategies for assessing chemotherapy need and efficacy, such as 2019 Papers In the Journal of the American Medical Association (JAMA), it shows that ctDNA may have an impact on the postoperative management of CRC, including guiding chemotherapy patient selection and optimizing chemotherapy duration.other study Research published in 2021 by Zhejiang University School of Medicine and Sun Yat-Sen University Cancer Center found a strong correlation between a positive ctDNA test result and the risk of recurrence. Even patients with stage III CRC who are ctDNA-negative after surgery have standard-of-care auto-adjuvant therapy—may not require chemotherapy, but can wait to see if their ctDNA results become positive. Since a large proportion of patients with stage III CRC can be cured by surgery alone, ctDNA-guided therapy could spare patients from unnecessary drug toxicity and the financial burden of chemotherapy.
Another example is CIRCULATE Japan’s GALAXY Study, I was the lead investigator, and found that the presence of ctDNA after surgery was more predictive of who would benefit from adjuvant chemotherapy (ACT) than any other factor, regardless of cancer stage. These results suggest that stratifying postoperative treatment decisions based on the presence of ctDNA could identify patients who are more likely to benefit from ACT at all stages, including stage II, and would be an improvement over the current standard of care.
Barriers to Adoption
Despite growing clinical evidence, the adoption of molecular testing as a complement to the current standard of care is a long way off and several hurdles must be overcome. First, while early studies are promising, more data are needed to demonstrate that patient outcomes can be improved through the use of these molecular-based early detection tools.
Furthermore, as the amount of evidence increases, ctDNA testing must be included in official guidelines. Current American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) guidelines do not address the clinical utility of molecular testing in guiding cancer treatment decisions after CRC surgery. Instead, they use risk-based factors as the basis for making treatment decisions, despite the fact that personalized cancer detection tests are clinically validated and now covered by Medicare in the U.S. Especially for stage II CRC, molecular testing can improve Standard of Care – As shown in the aforementioned GALAXY study, molecular testing can improve the standard of care for patients with stage II CRC and may spare many patients the unnecessary physical and economic toxicity of ACT.
Although a cure for cancer is still many years away, sensitive and reliable molecular detection tools can be used to help reduce the burden of cancer diagnosis.As resources are devoted to finding a cure, we should pay attention to the lives currently affected by this disease and how we can improve the way we care for this population now – in CRC alone, this is about 1.5 million peopleHelping patients recover from cancer as quickly as possible should be a top priority, and tools like molecular testing can help get the job done.
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