Rectal cancer patients who receive 1 week of radiotherapy prior to total mesorectal excision have a 50% reduction in the chance for local pelvic recurrence, according to a large randomized study presented at the plenary session of the 52nd Annual Meeting of the American Society for Radiation Oncology (ASTRO), held October 31-November 4 in San Diego. The Dutch trial, which followed more than 1,800 patients for a median of 11 years after treatment, found that the benefit of additional radiotherapy was most pronounced for patients with tumors in the middle rectum and those with stage III rectal cancer.

Key Data

"During the 1980s, local recurrence rates from rectal cancer ranged from 25% to 45%," commented Corrie Marijnen, MD, one of the lead authors of the study and a radiation oncologist at the Leiden University Medical Center in Leiden, Netherlands. "That has changed with total mesorectal excision. So the question became: Do we still need radiotherapy when surgery is performing so well?"

To answer that question, the Dutch researchers enrolled 1,861 patients with rectal cancer whose disease had spread outside of its original location but not to other parts of the body and randomly assigned them to total mesorectal excision alone or the surgery plus radiotherapy. Radiotherapy was given preoperatively at a dose of 5 × 5 Gy over 5 to 7 days.

After a median follow-up of 11 years, the local recurrence rate among those who underwent radiotherapy and surgery was 5.1%, compared with 11.1% for those who received total mesorectal excision alone (P < .001). Although radiotherapy significantly affected the chance of local recurrence, there was no difference in overall survival between the two groups.

Subgroup Analyses

The researchers performed a number of subgroup analyses, and found that patients diagnosed with stage III cancer derived the most benefit from radiotherapy compared to patients with stage I/II disease. Among patients with stage III disease, 19.2% experienced local recurrence after just total mesorectal excision, compared to 8.9% who experienced recurrence after radiotherapy plus total mesorectal excision (P < .001). However, patients with stage II disease also showed a trend toward reduced local recurrence rates after radiotherapy and total mesorectal excision vs surgery alone.

In the subgroup analyses, patients who had tumors with a height greater than 5 cm also benefitted more from additional radiotherapy than those with tumors less than 5 cm. The local recurrence rate in patients with tumors of 5 to 10 cm was 3.6% among those who received additional radiotherapy vs 13.8% among those who received surgery alone (P < .001). Among those with tumors between 10 and 15 cm, the local recurrence rate was 3.1% for the surgery-plus-radiotherapy group and 7.1% among those who received surgery alone (P = .04).

To the researchers' surprise, additional radiotherapy had a greater effect on patients with a negative circumferential resection margin (CRM) after surgery than those with positive margins. Local recurrence in CRM-negative patients who received additional radiotherapy was 3% vs 8.7% among those who received total mesorectal excision alone. Cancer-specific death was also significantly reduced in patients with a negative CRM who underwent radiotherapy and total mesorectal excision vs those who had surgery alone (16.9% vs 21.5%, P = .04)

The researchers concluded that although additional radiotherapy conferred no overall survival benefit, it did significantly reduce the chance of local recurrence-an effect likely to be crucial in maintaining patients' quality of life.

They recommended that patients with stage II/III rectal cancer should receive preoperative radiotherapy before total mesorectal excision, and also advised mandatory preoperative imaging with MRI. Although there is a need to reduce overtreatment in patients with rectal cancer, 1 week of preoperative radiation is safe and effective-and convenient for patients, Dr. Marijnen commented. ■

Reference

1. Marijnen CA, van Gijn W, Nagtegaal ID, et al: The TME trial after a median follow-up of 11 years. 52nd Annual ASTRO Meeting. Abstract 1. Presented November 1, 2010.