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WEDNESDAY, July 16, 2003 (HealthDayNews) -- Individuals whose colorectal cancer shows a specific genetic characteristic may not benefit from chemotherapy, which is often standard practice after surgery.
The findings, from a study appearing in the July 17 issue of the New England Journal of Medicine, form part of a larger movement to fine-tune cancer treatment to the individual.
"What we're looking for are specific aspects of tumors and genetic markers to see if they may be more amenable to more chemotherapy regimens," says Dr. Michael Spencer, an assistant clinical professor of surgery at the University of Minnesota in Minneapolis.
Colorectal cancer is the second-leading cancer killer and the fourth most commonly diagnosed cancer in the United States. According to the U.S. National Cancer Institute, women and men are equally at risk.
Tumors are usually removed with surgery but some individuals, especially those whose cancer has spread, are also advised to receive chemotherapy.
"In patients with a certain stage of the disease, the chance of recurrence is 50 to 60 percent," says Dr. Manish A. Shah, an assistant attending physician and gastrointestinal oncology specialist at Memorial Sloan-Kettering Cancer Center in New York City. "Chemotherapy reduces the chance of recurrence."
Or so doctors thought.
First, some basic genetics will help illuminate the study findings. All normal cells have areas where sequences of DNA repeat themselves. In tumor cells, however, the length of the repeated sequence can be longer or shorter than those in healthy cells. These so-called "microsatellite" areas can signal a problem with the body's ability to repair mistakes in cells.
"Errors do happen, but the body has checks and balances," Shah explains. "A breakdown happens when an error isn't picked up or it's picked up but the body doesn't care. A repeat is just a marker that cells aren't that good at repairing DNA." Once one error occurs, more mistakes happen downstream from that.
Cells with many sections of abnormal repeats are said to have "high-frequency instability." Cells with just a few such areas have "low-frequency instability," while those that have no such abnormalities are considered "stable." Some 85 percent of colorectal cancers exhibit low-frequency instability or stability, while the remaining 15 percent display high-frequency instability.
The authors of this multi-center study, which was led by researchers at Mount Sinai Hospital in Toronto, wanted to see if microsatellite status could predict how a patient responded to chemotherapy. To this end, they analyzed specimens from 570 patients with colon cancer who had participated in previous studies of chemotherapy. All the individuals had been diagnosed with stage II or stage III colon cancer and had been randomized into groups either receiving fluorouracil-based chemotherapy after surgery or just surgery.
Of the total 570 tissue specimens, 95 (16.7 percent) exhibited high instability, 60 (10.5 percent) demonstrated low instability and 415 (72.8 percent) were stable.
Interestingly, the patients with high instability had a better five-year survival rate when they did not receive chemotherapy than the other patients in the analysis who did not receive chemotherapy. Chemotherapy after surgery improved overall survival among patients with stable tumors or tumors displaying low instability.
The finding was not exactly a surprise. "It's an idea that's been around for the last five years as something, but it was not demonstrated as clearly as in this study," Shah says.
No one knows for sure why the results turned out the way they did, but there are theories. One possibility is the errors in the very unstable cells eventually accumulate to the point where they kill off the cells, Shah postulates. "The chemotherapy could cause the DNA to be more aggressive," he adds.
The question for physicians is whether they should be routinely checking microsatellite status in colorectal cancer patients, something which is relatively easy to do. "We haven't been checking, and maybe we should check," Shah says.
For the time being, however, the study authors and others caution that therapies should not be changed until there is more confirmation of the findings.
More information
For more on colorectal cancer, visit the American Society of Colon and Rectal Surgeons or the National Cancer Institute.
