Radiation And Chemotherapy Before Surgery Effective In Fight Against Rectal Cancer, UF Researchers Report

May 13, 1999

GAINESVILLE—The killing power of rectal cancer can be reduced sharply through a combination of radiation and drug therapy before surgery, University of Florida researchers report this month in the Annals of Surgery.

The approach also substantially decreases the likelihood that sufferers will have to endure one unpleasant side effect: a permanent colostomy, an artificial opening in the large intestine to allow the body to evacuate waste.

“Many tumors shrink in size dramatically with the combination therapy,” said Dr. Edward M. Copeland III, chairman of the department of surgery in UF’s College of Medicine. “We found that by adding chemotherapy to radiation, we could completely eliminate cancer cells in more of our patients before even going into surgery.

“The downstaging of the tumors also allows us to remove less tissue during surgery. This makes it easier to preserve the body’s normal waste elimination system.”

Rectal cancer strikes an additional 36,000 people each year in the United States, with an annual death rate of 8,800. It claims more victims than it has to: A report earlier this year by the U.S. Centers for Disease Control says that more than half of adults 50 and older fail to undergo the recommended screening tests to detect rectal or colon cancer, which together kill more than 55,000 people each year. The report suggests embarrassment, ignorance and fear of discomfort are partially to blame.

For decades, surgical removal of rectal cancer had been the recommended treatment. In the mid-1970s, UF physicians at Shands at UF medical center became among the first to use preoperative radiation to try to shrink some tumors to make them easier to remove. In 1991, UF physicians added the chemotherapy agent 5-flourouricil to the preoperative therapy. Later, they added a second drug, leucovorin, to the treatment.

“We are not the only physicians to have tried this combination pre-surgical approach, but because we have been using preoperative radiation therapy as long as anyone in the world, we have a large database of patients we can study,” said Copeland, who is the Edward R. Woodward professor of surgery.

Other major participants in the research included Dr. William M. Mendenhall, a professor of radiation oncology; Dr. Robert A. Zlotecki, an associate professor of radiation oncology; and Dr. Robert de W. Marsh, an associate professor of medicine.

The UF team compared outcomes for 219 people treated during the radiation and surgery era of 1975 to 1990 with 109 people treated from 1991 to 1997 whose therapy included the addition of preoperative chemotherapy. The patients all had locally advanced rectal cancer; some also had cancer spread to the lymph nodes.

The more recent group did better in several ways: For 28 percent, the pre-surgical therapy alone was enough to eliminate signs of cancer, compared with 8 percent in the earlier era.

Five-year survival rates also were expected to be higher in the radiation and chemotherapy group: an anticipated 87 percent vs. 58 percent. The rates are actuarial estimates based on the higher two-year survival rate of the group that received preoperative radiation and chemotherapy.

“Local recurrence of the cancer was about the same in both groups,” Copeland said. “The addition of chemotherapy to the treatment appears to have increased survival by reducing spread of the cancer to other parts of the body.”

Only 13 percent of patients in the combination group required a permanent colostomy following rectal cancer surgery, compared with 52 percent of the others. This difference between the two groups can be attributed to improved surgical techniques as well as the change in therapy, Copeland said.

“Our research suggests that preoperative radiation and chemotherapy is a promising approach for increasing survival,” Copeland said. “Our data potentially can be a springboard to the initiation of large randomized clinical trials, which would provide a higher standard of scientific evidence.”

Dr. Kirby I. Bland, chairman of surgery at Brown University School of Medicine, called the research “an important advance for the surgical and oncological communities.

“The premiere institutions have been using preoperative radiation and chemotherapy, but UF got a jump on the international community with data demonstrating its worth in this population,” said Bland, a former UF professor who participated in the early studies.