Short Course of Preoperative Radiotherapy Improves Outcomes in Patients With Resectable Rectal Cancer

ATLANTA—In patients with resectable rectal cancer, routine short-course preoperative radiotherapy results in a significant reduction in local recurrence and improved disease-free survival, compared with a selective postoperative approach. Furthermore, local recurrence is strongly related to the plane of surgical dissection, according to preliminary results of the Medical Research Council CR07 Trial. David Sebag-Montefiore, MD, of the Yorkshire Centre for Clinical Oncology, Leeds, United Kingdom, presented the results at the 42nd Annual Meeting of the American Society of Clinical Oncology (abstracts 3511 and 3512).

This was the first report from this phase III trial of 1,350 patients, a collaborative effort of the National Cancer Research Institute (NCRI) Colorectal Cancer Study Group and the National Cancer Institute of Canada (NCIC).

Patients with clinically operable adenocarcinoma of the rectum less than 15 cm from the anal verge and without metastatic disease were randomized to short-course preoperative radiotherapy (25 Gy in five fractions) followed by surgical excision and pathological examination of the circumferential resection margin (CRM) (the PRE group) or to surgery, followed by pathological examination (the POST group). CRM-negative patients received no postoperative irradiation while margin-positive patients received chemoradiation (45 Gy with concurrent 5-FU).

At a median follow-up of 3 years, all outcomes in the intent-to-treat analysis favored the PRE over the POST arm. Local recurrence rates were 5% vs 11% at 3 years and 5% vs 17% at 5 years, respectively (HR 2.47 , P < .0001). There were 34 fewer disease-related events in the PRE arm, mainly due to a reduction in local recurrence. Disease-free survival was improved from 75% to 80% at 3 years and from 67% to 75% at 5 years (P = .03). Five-year overall survival was 72% and 62%, respectively (P = .07), in the PRE and POST arms.

"In the PRE arm, the curve shows the local recurrence rate is rising very slowly, with very few local recurrences beyond 3 years. In contrast, the POST arm shows a continuing rise in local recurrence. Overall survival data are premature, but the curves are diverging as well," Dr. Sebag-Montefiore observed.

"The data confirmed findings from other trials that CRM status is a clear predictor of local recurrence, with a much lower rate seen in margin-negative tumors, compared with margin-positive tumors [7% vs 18% at 3 years]," he said.

In patients with negative CRM status, local recurrence was reduced from 10% to 3% in the PRE group (HR 2.91); CRM-positive patients in the PRE arm had a nonsignificant reduction from 23% to 16% (HR 1.56). "In CRM-negative patients there is a very clear treatment effect. You also see an effect of preo-perative radiotherapy on the CRM-positive patients, but it is too small a group (n = 193) to make definitive conclusions," he said.

A treatment effect for the PRE arm was seen across different tumor positions, sizes, and stages. By TNM stage, treatment effects were greatest for stage III patients, with a 3-year local recurrence rate of 9% vs 17% for the POST arm.

Plane of Dissection

In a second presentation (abstract 3512), Dr. Sebag-Montefiore reported that local recurrence was strongly related to the plane of surgical dissection. The 3-year local recurrence rate was 4% for the most optimal mesorectal plane, 8% for the intramesorectal plane, and 15% for the least optimal muscularis plane.

The best local recurrence rate was obtained for PRE patients with mesorectal plane dissection, 1% vs 6% in the POST group (HR 4.47). The fact that over half the cases (53%) involved the most optimal mesorectal plane "shows a high quality of surgical excision," Dr. Sebag-Montefiore said.