An easily detected genetic marker could help identify aggressive colon cancer in early stages, telling doctors that these patients need chemotherapy, a new study suggests.
Colon tumors that don't produce a protein called CDX2 are more likely to return following surgical removal in patients with stage 2 colon cancer, according to the study results.
Current standard practice holds that people with stage 2 colon cancer are not given chemotherapy following surgery to remove their tumors, because the risks of chemo outweigh the benefits, said study lead author Dr. Michael Clarke. He is a professor of cancer biology with the Stanford University School of Medicine in Palo Alto, Calif.
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But at least 5 percent to 10 percent of stage 2 patients are CDX2-negative, and therefore could benefit if doctors added chemotherapy to their treatment, Clarke said.
The study findings were published Jan. 21 in the New England Journal of Medicine.
Dr. Otis Brawley, chief medical officer for the American Cancer Society, said the new study is likely to change the way that cancer doctors treat stage 2 colon cancer patients.
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It wouldn't be difficult to put the test into practice, Brawley said. "Given this paper, I am going to be hard-pressed not to give these patients chemotherapy," he added.
People with stage 2 colon cancer generally have a favorable prognosis, Clarke and Brawley said. In this stage, the cancer has grown within the colon but has not yet spread to other parts of the body.
Patients with stage 2 colon cancer have a five-year survival rate of 63 percent to 87 percent, depending on the extent of the cancer throughout their colon, according to the American Cancer Society.
Progress in chemotherapy has improved survival rates during the past decade for advanced colon cancer. But, doctors have not been able to identify patients at earlier stages who might also benefit from these new chemo regimens, the study authors said in background notes.
Clarke and his colleagues decided to focus on colon cancer cells that appeared to function more like stem cells, which are not as tightly regulated by the body and thus are more likely to be aggressive.
The researchers landed on the CDX2 protein, which plays a role in determining how cells will be used to form the inner lining of the colon, Clarke said. Without CDX2, colon cells are less regulated and, therefore, cancerous cells are more likely to be aggressive.
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Another advantage of the CDX2 protein is that tumors can be screened using a simple antibody test, rather than requiring an expensive genetic scan, Clarke said. "That makes it much simpler for pathologists, and much less prone to error," he said.
To test their theory, the researchers analyzed medical data for nearly 1,900 patients with stage 2 or stage 3 colon cancer.The researchers found that about 4 percent of the patients had tumors that didn't produce CDX2.
In an initial study of 466 patients with any stage of colon cancer, only about 41 percent of those with CDX2-negative tumors lived disease-free for five years after treatment, compared to 74 percent of those with CDX2 in their cancer cells.
Further, patients whose tumor cells didn't express CDX2 were more likely to benefit from chemotherapy in addition to surgery than were people with CDX2-positive tumors.
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About 91 percent of patients with CDX2-negative cancers treated with surgery plus chemotherapy lived disease-free for five years, versus about 56 percent of those who did not receive chemotherapy, the study found.
Because this study did not involve a test on new patients, doctors can't be certain that this association is valid, Clarke warned.
"The data is extremely strong, but you need a prospective analysis to be 100 percent sure," he said. "It should be validated in a prospective trial."
The test could be put into practice right away, given that many laboratories can run this sort of antibody check on colon tumor cells, Clarke and Brawley said.
Brawley agreed that the study does not prove that chemotherapy will improve the outcome of patients with stage 2 colon cancer. "That is still a stretch," he said.
However, he expects cancer doctors will go ahead and give chemotherapy anyway to patients who are CDX2-negative.
The test likely will be applied only to stage 2 patients, however. That's because stage 3 colon cancer patients already get chemotherapy alongside surgery, Brawley said.
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