BESPOKE clinical trial supports value of blood test for colon cancer recurrence

The BESPOKE clinical trial evaluated molecular markers in blood samples as a guide that physicians can use to determine the benefit of chemotherapy for stage II and III colon cancer

According to the Centers for Disease Control and Prevention, more than 126,000 new cases of colon cancer (colorectal cancer) were diagnosed in 2020. Colon cancer is tricky because it rarely- produces symptoms, especially during the early stages of the disease. The best way to diagnose colon cancer is through early screening (colonoscopy). Once a patient is diagnosed, physicians can follow several courses of treatment, but the cancer can recur.

In recent years, researchers have been exploring how to use a molecular marker, ctDNA, circulating in blood to determine if colon cancer cells remain in the body after surgery. A multi-institutional team of researchers established the BESPOKE clinical trial to evaluate the use of ctDNA as a test that physicians can use when making decisions for patients after the initial treatment for colon cancer.

“I tell my patients, ‘your cancer is more than the tumor you see,’” said Timothy Cannon, MD, Co-Director of the Gastrointestinal Cancer Program at Inova Schar Cancer and a participating physician in the BESPOKE clinical trial. “There is now a tool available that helps physicians to better predict whether or not a person may benefit from chemotherapy after surgery and how well a person will respond to chemotherapy.”

The first step when treating colon cancer is surgery. Even when tumors are removed, tiny cancer cells can circulate throughout the body. This “micrometastatic disease” can seed cancer in other parts of the body. According to Dr. Cannon, it is difficult to identify these cancer cells among the trillions of other cells in the body, and many thousands of cancer cells may need to aggregate to become visible on a CT scan. The likelihood of micrometastatic disease is what determines whether chemotherapy is recommended. The current standard is for chemotherapy to be given for stage III and high-risk stage II cases of colon cancer.

Cancer cells have unique variants of proteins and DNA that can be shed into the bloodstream. These elements are different from those produced by normal cells. The ctDNA test is personalized and is based on the unique elements in the patient’s tumor. Each individual has a slightly different test created because their tumors have unique DNA and protein profiles. The ctDNA test is designed to find traces of these tumors.

The BESPOKE clinical trial focused on evaluating ctDNA as a potential test to identify recurrence of disease and inform the use of additional chemotherapy following surgery. In the clinical trial, tissue from the colon tumor was set aside for a genetic profile. This information was used to create a blood test unique to the patient’s specific cancer. According to Dr. Cannon, the blood test can be used to monitor a patient after surgery to see if cancer cells escaped and are circulating around the person’s body.

The  BESPOKE clinical trial involved researchers from multiple medical centers across the country. It recruited 1,792 participants, of which 350 were diagnosed at later stages (II = 154 or III = 196) of the disease.

The study followed participants on their treatment path. Physicians generally followed standard care patterns where patients with high-risk stage II and III cancer received traditional chemotherapy (either oxaliplatin based or fluoropyrimidine). The participants were stratified and followed based on their ctDNA results, but the physicians could choose whether or not the results would inform their decision about chemotherapy.

The researchers found that participants who were positive for ctDNA had a much higher risk (20 times) of recurrence of cancer than participants who were negative for ctDNA. In addition, participants who were positive for ctDNA and received additional chemotherapy had far longer disease-free survival compared to those in the observation/standard treatment group by the midpoint of the study.

“The results of the test tell a story that may prompt a physician to treat with chemotherapy after surgery more purposefully,” said Dr. Cannon. “Stage II colon cancer is considered high risk but the participants in the BESPOKE clinical trial found only nine stage II participants who were positive for ctDNA.”

Surprisingly, the disease-free survival for participants who were negative for ctDNA was not affected in either the chemotherapy or observation groups. Dr. Cannon believes the ctDNA-negative participants may not benefit from chemotherapy, though further confirmatory studies would be helpful. Following the current colon cancer recommendations, many patients with stage II or stage III disease undergo arduous chemotherapy therapy for no additional benefit.

The study supports the use of ctDNA as a guide that physicians can use in determining the likelihood of recurrence of colon cancer. It also provides insight on when to administer additional chemotherapy treatment following surgery. The results of the BESPOKE clinical trial will be further validated by additional ctDNA-directed randomized clinical trials. This approach has potential to treat other cancers where the primary method of distribution around the body is through the circulatory system.

“This test brings us closer to finding the cancer,” said Dr. Cannon. “If you can detect cancer in a blood sample several months after surgery, you can get ahead of the game.”

Dr. Cannon and his colleagues reported the results of the BESPOKE clinical trial during the American Society of Clinical Oncology Gastrointestinal Cancers Symposium in January 2024. Previous research on ctDNA was published in a 2022 New England Journal of Medicine article featuring results from the DYNAMIC clinical trial and the 2023 Nature Medicine article detailing the results from the GALAXY clinical trial.

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