Short Course of Radiation Therapy Before Total Mesorectal Excision Lowers Local Recurrence Rate

Selected rectal cancer patients who undergo optimal surgery with TME can still benefit from short-term preoperative radiation therapy.

In patients with resectable rectal cancer, preoperative, short-term radiotherapy may lower the risk of local recurrence by more than 50% a decade after optimal surgery, according to a study from the Netherlands. In a subgroup analysis, this large, randomized trial showed that radiotherapy appears to be most effective in patients with a negative circumferential resection margin, stage III disease, and tumor height more than 5 cm above the anal verge.

“We believe that this short course of radiation will open a new window of opportunity in the treatment of rectal cancer,” said lead author Corrie Marijnen, MD, PhD, a radiation oncologist at Leiden University Medical Center in Leiden. “Our study suggests that tumors in the middle rectum and stage III rectal cancer patients will benefit most from receiving radiation before surgery.”

Local recurrence is a major problem in rectal cancer treatment. Preoperative short-term radiotherapy has been shown to improve local control and survival in combination with conventional surgery. The Total Mesorectal Excision (TME) trial investigated the value of radiotherapy in combination with TME.

The trial included 1,805 patients with resectable rectal cancer who were randomized to TME preceded by 5 Gy of radiotherapy given once daily for 5 days (n = 897) or TME alone (n = 908). No chemotherapy was allowed. There was no age limit for the enrolled patients; the median age was 65 for the radiotherapy group and 66 for the surgery- only group. Surgery, radiotherapy, and pathological examination were standardized, and the primary endpoint was local control. The majority of patients in both groups were men.

The researchers found that the 10- year local recurrence rate was 6.4% in the irradiated group, compared with 13.3% in the surgery-alone group. While the overall recurrence rate was significantly lower in the irradiated group (28.8% vs 33.6%), the researchers were disappointed to find no difference in overall survival. At the time of the study presentation, all of the patients had been followed for a median of 11 years (ASTRO 2010 abstract 1).

“We think we should select our patients better to try to avoid overtreatment,” Dr. Marijnen said. “All patients should have TME surgery, and selected patients need preoperative radiotherapy.”

For patients with a negative circumferential resection margin (CRM), cancer-specific survival was higher in the irradiated group. In the subgroup analysis, radiotherapy only reduced local recurrence in the CRM-negative patients, lymph-node-positive patients, and patients with a tumor more than 5 cm from the anal verge. Among the node-positive patients with a negative CRM, preoperative radiotherapy significantly improved 10-year survival from 41% to 51%.

VANTAGE POINT

The value of preoperative radiotherapy in rectal cancer patients may actually be even greater than that seen in this study, said Dr. Willett, professor and chair of radiation oncology at Duke University in Durham, N.C. He noted that all the patients were treated between 1996 and 1999, but that now, in 2010, radiation treatment planning is more precise, allowing for conformal tumor targeting with reduction in normal tissue irradiation, and less side effects. In addition, early stage patients (unlike this trial) do not receive preoperative radiation therapy because of their favorable outcome with surgery alone.

“The data from this study were longterm outcome results, and it is an excellent piece of work,” Dr. Willett said. “It showed that even with the best surgery, the use of radiation therapy prior to surgery was beneficial.”

He pointed out the radiotherapy regimen used in this study differs from that commonly used in the U.S. Nonetheless, “I think the basic findings support the use of radiation therapy combined with surgery in the treatment of patients with rectal cancer,” Dr. Willett said.