Radiotherapy Before TME Reduces Rectal Cancer Recurrence

LISBON, Portugal—Short-term preoperative radiotherapy significantly lowers the risk of local recurrence in patients with rectal cancer who undergo standardized total mesorectal excision (TME), Cornelis J.H. van de Velde, MD, PhD, reported at the 11th European Cancer Conference (ECCO abstract 143). Dr. van de Velde, a University of Leiden surgeon, chairs the Dutch Colorectal Cancer Group.

Standardization and quality control were important foundations of the TME study. Dr. van de Velde reminded the audience that the 1997 Swedish Rectal Cancer Study, the first trial to establish the survival benefit of preoperative radiotherapy, documented a 27% local recurrence rate among patients treated with surgery alone.

In contrast, he emphasized, recurrence rates of only 10% have been reported following standardized, good anatomical surgery in which the circumferential margins are removed. So, the key question addressed by the TME trial was whether preoperative radiotherapy can enhance local control even after optimal surgical resection.

Standardization

To achieve standardization in the TME study, participating surgeons were required to perform five operations under the supervision of an "instructor surgeon" from another hospital before they were allowed to enter patients into the trial. Surgery quality-control priorities included nerve preservation, pouch anastomosis, and the avoidance of stomas by performing low anterior resections. Pathology standards were also instituted.

The study investigators randomly assigned 1,861 patients with resectable rectal cancer to receive radiotherapy, 5 Gy per day for 5 days, followed by TME a week later, or to undergo TME without radiation therapy.

Combining preoperative radiotherapy with TME reduced the 2-year local recurrence rate to 2.4%, compared with 8.2% among patients who underwent surgery alone (P < .001). No difference in overall survival has yet become apparent, Dr. van de Velde said.

More detailed results of the study can be found in the New England Journal of Medicine (345:638-646, 2001).

Margins

"Local recurrence correlated with margins," Dr. van de Velde said. The risk of recurrence was 12% with margins less than 2 mm but only 3% with larger margins. He stressed that the quality of the surgery can be measured by the completeness of the circumferential margins and the quality of the specimen.

Given the importance of circumferential margins, investigators need to ask whether preoperative radiotherapy can compensate for positive or narrow margins.

"When the margin was 1 to 2 mm, or even as large as 1 cm, there was a very significant effect of radiation therapy," Dr. van de Velde said. "When the margin was greater than 1 cm, there was no recurrence at all in the radiation-plus-surgery arm, whereas there was 10% recurrence in the surgery-alone arm." However, radiation therapy did not compensate for microscopic involvement (margins less than 1 mm).

Adverse Events

The chief drawbacks of combined-modality therapy were more intraoperative blood loss, more perineal wound dehiscence, higher postoperative mortality in the elderly, and more sexual dysfunction in men.

Men who received preoperative radiotherapy experienced a significantly higher rate of impotence (31% vs 21% with surgery alone, P = .03) and a threefold greater incidence of ejaculation abnormalities. In the future, devoting more attention to the superior hypogastric nerve should help to minimize sexual morbidity, Dr. van de Velde said.

Overall, the standardization measures implemented in the TME trial resulted in a local recurrence rate of 5%, irrespective of whether radiotherapy was given, compared with 30% in the past.

Additional successes included a reduction in the abdominal perineal resection rate to 30% (vs 40% in the past), more pouch reconstructions resulting in fewer bowel movements, a reduction in lateral margin involvement to 16% (vs 27% in the past), and a decrease in impotence to 26% (vs 35% in the past).

"Quality control trials are a fact, not a fantasy, and they contribute greatly to better treatment results," Dr. van de Velde commented.