Radiation therapy before surgery reduces rectal cancer recurrence

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A short course of radiation therapy followed by surgery is the most effective treatment for patients with operable rectal cancer, according to two studies published in this week's edition of the Lancet.

Previous trials have shown a reduction in local recurrence with radiotherapy and chemotherapy before or after surgery. However, radiotherapy is costly and is associated with an increased likelihood of long-term complications, including impaired bowel function, incontinence and sexual dysfunction. Therefore, the researchers suggested that targeting radiotherapy to patients considered at high risk of local recurrence, such as those with involvement of the circumferential resection margin, would be ideal.

To provide further evidence, Robert Steele, MD, and colleagues conducted the Medical Research Council (MRC) CR07 and the National Cancer Institute of Canada (NCIC) C016 trial. The study compared the selective use of chemoradiotherapy after surgery for patients who had involvement of the circumferential resection margin with the routine use of a one week course of radiotherapy before surgery, on the risk of local recurrence.

In total, the researchers recruited 1,350 patients with rectal cancer from the United Kingdom, Canada, South Africa and New Zealand between March 1998 and August 2005. Patients were randomized to receive five daily treatments of radiotherapy followed by surgery, or surgery followed by 25 treatments of chemoradiotherapy for those at high risk of local recurrence.

Steele and colleagues found that after three years, 4.4 percent of patients in the preoperative radiotherapy group had local recurrence of the cancer compared with 10.6 percent of patients in the postoperative group. In addition, preoperative radiotherapy patients had a greater likelihood of disease-free survival (77.5 percent) than the postoperative patients (72 percent) at three years. However, overall survival did not significantly differ between the groups-330 patients died (157 in the preoperative radiotherapy group vs. 173 in the selective postoperative chemoradiotherapy group).

Recent improvements in surgical techniques, including total mesorectal excision have also improved patient outcomes. In a second study, Phil Quirke, MD, from the University of Leeds in England, and colleagues assessed the importance of circumferential resection margin and the plane of surgery achieved by the surgeon on local recurrence of cancer, in 1,156 patients involved in the MRC CR07 and NCIC-CTG C016 trial.

Quirke and colleagues found that 128 patients had involvement of the circumferential resection margin, and the plane of surgery was classified as good (mesorectal) in 604, intermediate (intramesorectal) in 398 and poor (muscularis propria plane) in 154.

A negative circumferential resection margin and a superior plane of surgery were associated with low recurrence rates. At three years, Quirke and colleagues found that 6 percent of patients with a negative circumferential margin had local recurrence compared with 17 percent of patients with a positive circumferential margin. In addition, 4 percent of patients in the mesorectal group had local recurrence compared with 7 percent of patients in the intramesorectal group, and 13 percent of patients in the muscularis propria plane group, at three years. However, for any plane of surgery achieved, short-course radiotherapy before surgery reduced recurrence by about half.

"At present, only 50 percent of rectal cancer surgery is done in the mesorectal plane, suggesting that a further decrease in local recurrence rates might be obtained by improving the plane of surgery achieved...[This could] be achieved through education and surgical tuition," Quirke and colleagues wrote.

In an accompanying commentary, Robert Madoff, MD, from the University of Minnesota in Minneapolis, wrote that these findings showed that "preoperative radiation can mitigate but not eliminate the adverse effects of imperfect surgery. The best outcomes occurred when preoperative radiation was followed by optimum surgery...The next challenge is to understand which patient needs what therapy to maximize his or her chance for cure."