Clinical Investigation
External Pelvic and Vaginal Irradiation Versus Vaginal Irradiation Alone as Postoperative Therapy in Medium-Risk Endometrial Carcinoma—A Prospective Randomized Study

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Purpose

To evaluate the value of adjuvant external beam pelvic radiotherapy as adjunct to vaginal brachytherapy (VBT) in medium-risk endometrial carcinoma, with regard to locoregional tumor control, recurrences, survival, and toxicity.

Methods and Materials

Consecutive series of 527 evaluable patients were included in this randomized trial. Median follow-up for patients alive was 62 months. The primary study endpoints were locoregional recurrences and overall survival. Secondary endpoints were recurrence-free survival, recurrence-free interval, cancer-specific survival, and toxicity.

Results

Five-year locoregional relapse rates were 1.5% after external beam radiotherapy (EBRT) plus VBT and 5% after vaginal irradiation alone (p = 0.013), and 5-year overall survival rates were 89% and 90%, respectively (p = 0.548). Endometrial cancer-related death rates were 3.8% after EBRT plus VBT and 6.8% after VBT (p = 0.118). Pelvic recurrences (exclusively vaginal recurrence) were reduced by 93% by the addition of EBRT to VBT. Deep myometrial infiltration was a significant prognostic factor in this medium-risk group of endometrioid carcinomas but not International Federation of Gynecology and Obstetrics grade or DNA ploidy. Combined radiotherapy was well tolerated, with serious (Grade 3) late side effects of less than 2%. However, there was a significant difference in favor of VBT alone.

Conclusions

Despite a significant locoregional control benefit with combined radiotherapy, no survival improvement was recorded, but increased late toxicity was noted in the intestine, bladder, and vagina. Combined RT should probably be reserved for high-risk cases with two or more high-risk factors. VBT alone should be the adjuvant treatment option for purely medium-risk cases.

Introduction

Five prospective randomized studies conducted since 1980 are presented to elucidate the value of external beam pelvic radiotherapy after surgery in early-stage endometrial carcinoma (including the study by Alders et al. [Aalders] [1], Postoperative Radiation Therapy in Endometrial Carcinoma protocol 1 [PORTEC-1], Gynecologic Oncology Group study 99 [GOG-99], A Study in the Treatment of Endometrial Cancer (ASTEC/EN.5), and PORTEC-2 [2-5]). In three of these studies, vaginal brachytherapy (VBT) was also part of the treatment (Aalders, ASTEC/EN.5, PORTEC-2) 1, 4, 5, and in the other two studies (PORTEC-1, GOG-99) 2, 3, external irradiation alone was compared, with no further treatment after primary surgery. The treated populations varied in these studies from groups with no defined risk (Aalders) (1) to a mixture of low-risk (PORTEC-1, GOG-99) 2, 3, medium-risk (PORTEC-1, GOG-99, ASTEC/EN.5, PORTEC-2) 2, 3, 4, 5, and high-risk cases (ASTEC/EN.5) (4). Types of primary surgery and staging also varied from no staging at all (Aalders, PORTEC-1, ASTEC/EN.5, PORTEC-2) 1, 2, 4, 5 to staging with lymph node sampling or complete lymphadenectomy (GOG-99, ASTEC/EN.5) 3, 4. Subgroup analyses performed within the framework of these studies suffered from low power and no level 1 data are presented for well-defined medium-risk and high-risk groups. The general conclusions drawn from these studies are a significantly lower rate of locoregional pelvic recurrences, similar survival rates, and increased bowel toxicity after external pelvic irradiation. The problems seem to be vaginal recurrences, distant metastases, and quality of life. VBT is a more nontoxic alternative to external beam radiotherapy (EBRT) in preventing vaginal recurrences (PORTEC-2 and PORTEC-2 quality of life) 5, 6, and chemotherapy is probably required to reduce the number of distant metastases and to improve survival (7).

A prospective randomized trial is presented from five Swedish gynecological cancer centers to compare VBT alone with a combination of VBT and external beam pelvic irradiation in a well-defined group of medium-risk endometrial carcinomas. Thus, this study differs from all of the five published studies presented above.

The primary study endpoint was locoregional tumor control (pelvic recurrences and vaginal recurrences) and overall survival rate. Secondary endpoints were cancer-specific survival rate, recurrence-free interval and survival, and toxicity.

Section snippets

Patients

Five Swedish cancer centers (Gothenburg, Örebro, Umeå, Uppsala, and Stockholm) recruited patients with medium-risk International Federation of Gynecology and Obstetrics (FIGO) Stage IA-IC endometrial carcinomas into this prospective, randomized, and controlled study. The period of recruitment was from January 1997 through February 2008. In all, 562 patients (arm A = 285 and arm B = 277 patients) were included in the trial. At the time of follow-up, 527 patients were evaluable for analysis.

Recurrence rate

The overall recurrence rate for the complete series was 42 of 527 cases or 8.0%. In the group treated with EBRT plus vaginal irradiation (arm A), 15 recurrences in 264 cases (5.7%) were recorded; and in the group treated with vaginal irradiation alone (arm B), 27 recurrences in 263 cases (10.3%) were recorded (Pearson chi-square, p = 0.052). Five vaginal recurrences (1.9%) were diagnosed in the combined treatment arm and 7 recurrences after vaginal irradiation alone (2.7%) (Pearson chi-square, p

Discussion

Postoperative treatments of FIGO Stage I endometrial carcinoma have been vividly discussed and also studied in a number of randomized trials during the last decade 1, 2, 3, 4, 5. Before that, no consensus existed with regard to type of therapy, but the situation has changed, and our evidence-based knowledge in this field has improved substantially. However, different conclusions are still drawn from available study data, and the optimal treatment of the various risk groups is continuously

Conclusions

In this study, we have shown that combined EBRT and VBT was superior to VBT alone in improving locoregional tumor control in medium-risk endometrial cancer patients. This might be of benefit to the patients. However, questions of cost effectiveness, radiation-induced side effects (17), and lack of a survival benefit for this risk group must be taken into account.

Future radiotherapy studies of this risk group of endometrial carcinoma patients should address new and improved techniques (e.g.,

References (23)

  • P. Blake et al.

    Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): Pooled trial results, systematic review, and metaanalysis

    Lancet

    (2009)
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    Conflict of interest: none.

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