ArticlesSurgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial*
Introduction
Endometrial carcinoma is the most common gynaecological cancer, having an incidence in western countries of 15–20 per 100 000 women per year.1 75–80% of endometrial cancers are diagnosed at an early stage (International Federation of Gynaecology and Obstetrics [FIGO] stage I). The most significant prognostic factors are tumour stage, histological grade, and depth of myometrial invasion. Others are age, histological type, peritoneal cytology, vascular space invasion, progesterone receptor activity, menopausal stage, and uterine size.2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 Total abdominal hysterectomy and bilateral salpingooophorectomy is the cornerstone of treatment. If risk factors are present, that is, myometrial invasion to 50% or more of the myometrial width and/or grade 2 or 3 histology, pelvic radiotherapy is indicated to reduce the risk of pelvic relapse. The value of postoperative radiotherapy in the treatment of patients with stage-1 endometrial carcinoma is, however, controversial due to a lack of data from randomised studies and the low relapse rate.14 Patients with stage-1 endometrial carcinoma treated with surgery and postoperative radiotherapy have a 5-year overall survival of 80–90%, a 5-year cancer-specific survival of 90–95%, and locoregional recurrence rates of 4–8%.2, 5, 6, 9, 12, 15, 20 However, patients with grade-3 tumours with deep myometrial invasion have a much higher risk of relapse.2, 5, 7, 19 Only one randomised study has been reported, in which 540 women who had had postoperative vaginal radiotherapy were randomly assigned to additional pelvic radiotherapy or observation.2 Although pelvic radiotherapy reduced vaginal and pelvic recurrence (2% vs 7%), more distant metastases were found in the pelvic radiotherapy group (10% vs 5%), and survival was not improved (89% vs 91% at 5-years). Only the subgroup with grade-3 tumours with deep (≥50%) invasion showed both improved local control and survival after additional pelvic radiotherapy.
In retrospective studies of stage-1 endometrial carcinoma treated surgically followed by radiotherapy in case of poor prognostic factors, relapse rates of 15–20% are reported, of which 4–7% are locoregional recurrences and 7–17% distant metastases.5, 6, 9, 12, 15, 16, 17, 18, 19, 20, 21 Most locoregional relapses are in the vagina, mainly in the vaginal vault. In previously unirradiated patients the salvage rate for isolated vaginal relapse is 40–80%.8, 14, 15, 22, 23, 24, 25, 26, 27 The salvage rate of extravaginal pelvic relapse is low, ranging from less than 5% for patients who have received previous pelvic radiotherapy to 20–30% in those not previously irradiated.14, 15, 23, 27, 28 In the Gynaecological Oncology Group (GOG) staging study,4 the risk of pelvic node metastases in surgical stage-1 endometrial carcinoma was less than 10%, except for the subgroup with grade-3 tumours, in whom the risk was 18%.
A multicentre prospective randomised trial was initiated to establish the role of postoperative pelvic radiotherapy in FIGO stage-1 endometrial carcinoma, based on the following rationale: the locoregional relapse rate of stage-1 endometrial cancer is low; the efficacy of radiotherapy has never been established in a randomised trial; lymphadenectomy studies4, 29 show an incidence of pelvic lymph node involvement in surgical stage-1 endometrial carcinoma of less than 10%; the salvage rate of vaginal relapses in previously unirradiated patients is high. Patients with grade-1 tumours with deep myometrial invasion, grade-2 tumours with any invasion, or grade-3 tumours with superficial invasion were randomly assigned to either postoperative pelvic radiotherapy or no further treatment. The objectives of the Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC) study were to compare locoregional control, overall survival, and treatment-related morbidity of patients with stage-1 endometrial carcinoma, treated with postoperative pelvic radiotherapy or surgery alone.
Section snippets
Patient selection and eligibility criteria
All but one of the 20 radiation oncology centres in the Netherlands took part. The patients were evaluated and treated by their local gynaecologist, most often a general gynaecologist with special interest in gynaecological oncology. Initial evaluation included a pelvic examination, and endometrial curettage with separate endocervical and endometrial sampling. Preoperative evaluation included a medical history and physical and pelvic examination, chest radiography, complete blood count, and
Results
715 patients with stage-1 endometrial carcinoma were enrolled in the study between June, 1990, and December, 1997. 354 patients were randomly assigned to postoperative pelvic radiotherapy and 361 to no further treatment. 714 patients could be evaluated (figure 1)
The study groups were well balanced for characteristics such as age and concurrent morbidity and histological type and grade and myometrial invasion (table 1). Ten patients (four in the radiotherapy group, six in the control group) were
Discussion
Our results show that postoperative radiotherapy improves locoregional control—but this improvement did not translate into a survival benefit. Overall 5-year survival was 85% in the controls and 81% in the radiotherapy group. The proportion of patients who suffered an endometrial cancer-related death was larger in the radiotherapy group (9% vs 6%, p=037). Survival rates in both groups accorded with data from retrospective studies2, 5, 6, 9, 12, 13, 15, 16, 17, 18, 19, 20 of stage-1 endometrial
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