Radiotherapy Added to Surgery Lowers Recurrence Rates in Rectal Cancer

Roxanne Nelson

October 28, 2010

October 28, 2010 — Neoadjuvant radiation therapy can reduce the rate of local recurrence in rectal cancer by more than 50%. But although a short course of radiation therapy significantly lowered the recurrence rate, it did not translate into an improvement in overall survival, according to study findings.

For patients who received radiation before surgical resection, the 10-year local recurrence rate was 6.4%, compared with 13.3% for patients who had surgery alone (P < .001).

Overall recurrence was significantly lower in the group that received radiation than in the group that did not (28.8% vs 33.6%; P = .042), according to lead author Corrie Marijnen, MD, from Leiden University Medical Center in the Netherlands.

"To our surprise, radiotherapy was the most effective in patients with negative circumferential resection margins," said Dr. Marijnen, who reported her findings at a press briefing held in advance of the American Society for Radiation Oncology (ASTRO) 52nd Annual Meeting.

Cancer-specific survival was higher in patients who received radiation therapy and had circumferential resection margins, Dr. Marijnen noted. In a subgroup analysis, lymph-node-positive patients with negative circumferential resection margins who received preoperative radiotherapy improved their 10-year survival from 41% to 51% (P = .02).

Radiation Unnecessary?

Anthony L. Zietman, MD, president of ASTRO and moderator of the press briefing, noted that rectal cancer is usually managed surgically, and to prevent recurrence in the pelvis, radiation has traditionally been administered.

But in recent years, surgeons have moved toward a wide surgical resection technique known as total mesorectal excision (TME). "The question is: Does TME render additional radiation unnecessary?" Dr. Zietman said. "This trial sought to address that question. The extraordinary strength of this study is its size and maturity."

Benefit Seen in Subgroups

In this trial, Dr. Marijnen and colleagues evaluated the use of preoperative short-term radiotherapy combined with TME. Training was an essential component of this study, and all surgeons at participating centers had reached a level of expertise in TME.

They randomized 1861 patients with resectable rectal cancer to either TME preceded by 5 x 5 Gy radiotherapy or TME alone; none of the patients received chemotherapy. The primary end point was local control. Median follow-up was 11 years.

Although local recurrence was lower in the radiation group than in the TME group, it appeared that the benefit was primarily limited to certain subgroups within the cohort. In subgroup analyses, radiotherapy only appeared to reduce local recurrence in patients with a negative circumferential resection margin, with a stage III tumor, and with a tumor more than 5 cm from the anal verge.

There was no difference in survival when the entire trial population was analyzed on an intention-to-treat basis, the authors note, adding that future staging techniques might offer the ability to select patient groups that will obtain a survival benefit.

"This study shows that patients with stage II and III disease should receive radiation therapy before surgery to prevent recurrence and preserve quality of life," said Dr. Marijnen. "We have advised that in all our Nordic countries, patients with stage II and III rectal cancer will get this short course of preoperative radiotherapy before their TME surgery."

Dr. Marijnen noted that radiotherapy appears to be very safe, although the incidence of adverse events was higher in the group that received radiation.

"We are trying to refine the way we treat patients by refining surgery and the selective use of radiotherapy," said Dr. Zietman.

American Society for Radiation Oncology (ASTRO) 52nd Annual Meeting: Abstract 1. To be presented November 1, 2010.

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