A Phase III Trial of Surgery With or Without Adjunctive External Pelvic Radiation Therapy in Intermediate-Risk Endometrial Adenocarcinoma: A Gynecologic Oncology Group Study

Abstract

Between June 1987 and July 1995, 448 women with endometrial cancer were enrolled in a prospective, randomized trial comparing the use of postoperative radiation versus no postoperative treatment. Participants had stage IB, IC, II, or IIB endometrial adenocarcinoma with an intermediate risk of recurrence (that is, tumor with any degree of myometrial invasion, adenocarcinoma of any grade, and no evidence of lymph node involvement). In addition, an analysis was performed of 2 subgroups. High-risk patients had all of these risk factors: moderate to poorly differentiated tumor, presence of lymphvascular invasion, and myometrial invasion to the outer third; they were 50 years of age or older with 2 of the 3 risk factors; or they were 70 years of age or older and had one additional risk factor. Women who did not qualify for the high-risk subgroup were considered in the low-risk subgroup. Three hundred ninety-two participants met all eligibility requirements for inclusion in the analysis. Two hundred two women were randomized to the whole pelvic radiation group, and 190 received no additional postoperative treatment. Otherwise, both groups had similar clinical and demographic characteristics. In the radiation therapy (RT) group, 13 patients refused postoperative treatment and 5 received less than the prescribed dose. In the no-treatment group, 2 patients received fall-dose postoperative RT. Twenty-four participants were lost to follow up within a median of 50 months. Overall median follow up was 68 months. Forty-four patients, 31 in the unirradiated group and 13 in the radiation group, developed disease recurrence. After a median follow up of 80 months, 15 of the women who recurred were alive with disease. In all, 66 women in the study died, 32 from disease or treatment-related causes. Women who received postoperative radiation therapy were less likely to have a recurrence of disease than those who had no additional treatment Among the 202 patients who had no postoperative treatment, 13 recurred in the vagina, 4 in the pelvis, 1 in the vagina and pelvis, and 13 had distant recurrences. In the RT group, 2 women, both of whom refused treatment with radiation, had a recurrence in the vagina. One other patient recurred in the vagina and pelvis, and 10 had distant recurrences. Patients who were treated with postoperative radiation therapy had a 58% lower risk of ever having a recurrence of disease than women who did not. The overall risk of recurrence in the first 24 months after treatment was 3% (90% confidence interval [CI], 0.02-0.06) for women who received RT and 12% (90% CI, 0.09-0.17) for women who had no additional treatment. The estimated cumulative risk of recurring in the vagina or pelvis within the first 24 months was 1.6% (90% CI, 0.6-3.9) for those in the RT group compared with 7.4% (90% CI, 4.9-11.0) for the no additional treatment group. In the 132 women who were in the high-risk subgroup, 28 (28 of 44; 64%) had a recurrence of disease and 22 died from disease (22 of 32; 67%). The estimated risk of recurrence for high-risk women was 0.46 (90% CI, 0.19-1.11) compared with 0.42 (90% CI, 0.21-0.83) for low-risk women. There were 2 deaths from intestinal injury associated with radiation treatrnent. Overall, there were 6 instances of bowel obstruction in the RT group and 1 in the no additional treatment group.