The test promises a more accurate picture of the extent of disease
Scientists at Jefferson Medical College have devised a blood test they believe will tell patients whether their colorectal cancer has returned. The test looks for the presence of a protein, GCC, to detect the spread of colorectal cancer to the lymph nodes. It may help doctors better diagnose the disease and provide more appropriate treatment.
Scott Waldman, M.D., Ph.D., Samuel M.V. Hamilton Family Professor of Medicine and director of the Division of Clinical Pharmacology at Thomas Jefferson University in Philadelphia, and his Jefferson co-workers compared two groups of 21 colorectal cancer patients each. One group consisted of patients who had been disease-free for at least six years and deemed "cured." The other group of patients developed recurrent disease within three years after cancer surgery. The latter patients had also been told initially that they had no signs of cancer in their lymph nodes after surgery, meaning their cancer had not spread.
The scientists examined lymph node samples of each patient for the presence of GCC. They found that the disease-free patients' lymph nodes showed no signs of the protein marker. Conversely, GCC was present in every patient whose cancer had returned. They report their results Dec. 7 in the Annals of Internal Medicine.
"The findings suggest that the test can be used to detect metastatic colorectal cancer during the staging of these patients," Dr. Waldman says. "It is more sensitive than current histological methods and the results correlate with disease progression."
Colorectal cancer is the third most common cancer in the nation, with some 200,000 new cases diagnosed annually. It is the fourth leading cause of cancer deaths, and like most cancers, is best treated when found early. Both surgery and chemotherapy are more effective when the disease is still in the intestine. "The single best predictor of how a patient does is whether the disease is confined to the intestine," Dr. Waldman says. "If microscopic seeds have escaped to the lymph nodes, then when a surgeon takes out the cancer, he invariably leaves some behind."
According to Dr. Waldman, as many as 40 percent of colorectal cancers originally thought cured by surgery alone return within about three years.
Staging is the standard way to diagnose cancer. Surgeons remove lymph nodes during surgery and pathologists then examine them under a microscope to look for cancer cells. But the technique all too often misses cancer cells, and physicians would like a more sensitive and accurate method to find disease in the lymph nodes.
That's one reason Dr. Waldman and his co-workers have doggedly searched for such a method. If these initial results hold up in larger clinical trials, he says, doctors may be able to use the test immediately for diagnosing metastatic disease.
"Surgeons can remove the primary tumor and we can confirm the diagnosis using this testing," he explains. "We can use the test for staging - we can get pieces of lymph node and tell patients if they have disease inside or outside the intestine, which is important in deciding about chemotherapy.
"We hope this marker is sensitive and specific for metastatic colorectal cancer," he says. "We want to be able to take lymph nodes judged clean by pathologists in patients told they have disease confined to the intestines, and find disease we wouldn't have found until much later."
Dr. Waldman sees the marker as a useful diagnostic tool for the long run as well. "This marker may be used as a blood test to follow patients after they've had what's thought to be definitive surgery to determine if they have recurrent disease," he explains. "A patient can return for a routine follow-up periodically for blood tests to look for metastatic colorectal cancer cells to know that in fact that he is not in recurrence. If he is, we can possibly intervene sooner."
But, Dr. Waldman says, the study results are only a first step. "It was a small subgroup and this is a retrospective study, conducted after the patients had been diagnosed - we knew ahead of time their diagnoses and we specifically selected them. Now we want to do a large prospective study."
He plans to enroll between 1,000 and 2,000 patients in a large, prospective 5-year study comparing the ability of the standard histological examination of lymph nodes to that of the GCC marker test to predict recurrent disease.
GCC, or guanylyl cyclase C, is a family of seven proteins expressed only by intestinal cells and colorectal cancer cells. It's vital to cellular communications, transmitting signals from outside to inside the cell. It turns out that most sporadic colorectal cancers originate in the cells that line the intestine - cells that normally make GCC. When the cells become cancerous, they continue to make GCC.
The work was funded by the National Institutes of Health and by Targeted Diagnostics & Therapeutics, Inc. (TDT), a privately held biotechnology company based in Exton, Pa. Dr. Waldman is chair of the company's scientific advisory board.
Under the research agreement between TDT and Jefferson, Jefferson owns all patents and the worldwide rights are licensed exclusively to TDT.
Journal
Annals of Internal Medicine