ArticlesVaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial
Introduction
Endometrial carcinoma is the most common gynaecological malignant disease in postmenopausal women in developed countries.1 About 80% of patients present with early stage disease (International Federation of Gynecology and Obstetrics [FIGO] stage I, limited to the uterine corpus) and have a favourable prognosis. Surgery consisting of total abdominal hysterectomy and bilateral salpingo-oophorectomy is the basis of treatment.
Both the first Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC-1) trial2, 3 and the Gynecological Oncology Group (GOG) 99 trial4 compared pelvic external beam radiotherapy (EBRT) with no additional treatment for patients with stage I endometrial carcinoma, and showed that EBRT significantly reduced the rate of locoregional (vaginal or pelvic, or both) recurrence. Both trials defined a so-called group of high-intermediate risk that showed the largest absolute reduction of locoregional recurrence after EBRT. In PORTEC-1, major risk factors for recurrence were invasion in the outer half of the myometrium, grade 3 histology, and age greater than 60 years.2, 3 For patients at high-intermediate risk with two of these three major risk factors, locoregional recurrence at 5 years was reduced from 23% to 5% after EBRT.2, 3 In GOG 99, EBRT provided a 58% hazard reduction of 4-year cumulative recurrence in the group at high-intermediate risk (from 27% to 13%), and reduction of isolated initial local recurrence from 13% to 5%.4 In both trials this reduction was mainly caused by reduction of vaginal recurrence, which accounted for 75% of locoregional recurrence in the group receiving no additional treatment. EBRT did not improve overall survival, and rates of distant metastases were similar. In PORTEC-1, adverse effects were recorded in 26% of patients receiving EBRT, predominantly mild gastrointestinal toxic effects.5
Retrospective studies reported vaginal brachytherapy (VBT) to be very effective in prevention of vaginal recurrence.6, 7, 8, 9, 10 The randomised PORTEC-2 trial was started to investigate whether VBT would be equally effective as EBRT in reduction of vaginal recurrence, with fewer treatment-related toxic effects and improved quality of life. Analysis of quality of life reported by patients in PORTEC-2 during the first 2 years after treatment has shown that those who had received EBRT reported significantly more, clinically relevant gastrointestinal symptoms, especially diarrhoea,11 resulting in restriction of daily activities and decreased social functioning.
This study aimed to compare outcomes and adverse effects after VBT and EBRT, and to establish optimum adjuvant treatment for patients with endometrial carcinoma of high-intermediate risk.
Section snippets
Patient selection and eligibility criteria
The PORTEC-2 trial was a multicentre randomised trial, in which 19 of the 21 Dutch radiation oncology centres participated. The study was undertaken between May 27, 2002, and Sept 25, 2006. Patients were assessed and operated on by their regional gynaecologist. Initial assessment included pelvic examination and endometrial tissue biopsy. Preoperative assessment included chest radiography and haematology and chemistry tests. During surgery a peritoneal cytology specimen was obtained and
Results
Figure 1 shows the trial profile. 427 patients were randomly allocated to EBRT (n=214) or VBT (n=213). Data were frozen for analysis on May 19, 2009, and all patients were entered in the intention-to-treat analysis. Patient and tumour characteristics were well balanced between the groups (table 1). Table 2 shows radiotherapy details.
23 (5%) protocol violations occurred, of which 12 (3%) were major (seven in EBRT group, five in VBT group). 11 patients did not receive the allocated treatment, one
Discussion
The PORTEC-2 trial compared the efficacy and toxicity of EBRT and VBT for endometrial cancer of high-intermediate risk. At a median follow-up of 45 months, very few vaginal recurrences occurred in both treatment groups, showing VBT to be very effective in ensuring of local control. The vaginal recurrence rate after EBRT is very similar to the rate of 2·2% at 5 years in the first PORTEC trial in patients at intermediate risk, showing consistency of this main finding in both trials.2
After
References (23)
- et al.
Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial
Lancet
(2000) - et al.
Postoperative radiotherapy for Stage 1 endometrial carcinoma: long-term outcome of the randomized PORTEC trial with central pathology review
Int J Radiat Oncol Biol Phys
(2005) - et al.
A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study
Gynecol Oncol
(2004) - et al.
The morbidity of treatment for patients with Stage I endometrial cancer: results from a randomized trial
Int J Radiat Oncol Biol Phys
(2001) - et al.
Intravaginal brachytherapy alone for intermediate-risk endometrial cancer
Int J Radiat Oncol Biol Phys
(2005) - et al.
High-dose-rate postoperative vaginal cuff irradiation alone for stage IB and IC endometrial cancer
Int J Radiat Oncol Biol Phys
(2000) - et al.
Patterns of failure in endometrial carcinoma stage IB grade 3 and IC patients treated with postoperative vaginal vault brachytherapy
Gynecol Oncol
(1999) - et al.
Stage II endometrial carcinoma: limiting post-operative radiotherapy to the vaginal vault in node-negative tumors
Gynecol Oncol
(2005) - et al.
Adjuvant vaginal high-dose-rate afterloading alone in endometrial carcinoma: patterns of relapse and side effects following low-dose therapy
Gynecol Oncol
(1998) - et al.
Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC)
Int J Radiat Oncol Biol Phys
(1995)
CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment
Semin Radiat Oncol
Cited by (944)
Impact of molecular profile on prognosis and relapse pattern in low and intermediate risk endometrial cancer
2024, European Journal of CancerIncidence of Secondary Cancers After Neoadjuvant Therapy for Locally Advanced Rectal Cancer
2024, Journal of Surgical Research