Elsevier

The Lancet Oncology

Volume 10, Issue 11, November 2009, Pages 1119-1127
The Lancet Oncology

Review
Management of endometrial cancer in Asia: consensus statement from the Asian Oncology Summit 2009

https://doi.org/10.1016/S1470-2045(09)70290-6Get rights and content

Summary

Endometrial cancer is one of the gynaecological cancers that carries good overall prognosis because it is often detected at early stages of disease. The International Federation of Gynecology and Obstetrics replaced clinical staging with surgical staging in 1988 and updated the system in 2009. Controversies remain regarding the recommended screening protocol for women with a high risk of endometrial cancer, the role and benefit of retroperitoneal lymph-node dissection, the necessity of ovarian resection, the benefit and type of adjuvant radiation therapy, and the safety of hormone-replacement therapy after treatment. This article reviews the available evidence for optimum management of endometrial cancer and how management strategies can be applied in Asian countries with different levels of health-care resource availability and economic development. An overview of the literature for endometrial-cancer screening, diagnosis, and management is discussed. Consensus statements are formulated on the basis of basic, limited, enhanced, and maximum health-care resource availability, using the framework provided by the Breast Health Global Initiative.

Introduction

Endometrial cancer, the seventh most common cancer in women worldwide, is probably more important in terms of number of new cases than in terms of mortality (representing 3·9% of new cancer cases in women compared with 1·7% cancer deaths annually).1 Although the incidence of endometrial cancer is lower in developing countries than in developed areas, the ratio of mortality to incidence is somewhat higher. In developing countries, the mortality-to-incidence ratio is 21 000 to 62 000 (0·34) and the age-adjusted 5-year overall survival is 67%, compared with figures of 29 000 to 136 000 (0·21) and 82% in developed areas.1

Endometrial cancer (figure) seems to arise through two different pathophysiological pathways; type I involves exposure to high concentrations of oestrogen and type II is independent of hormone exposure.2 Type I is represented by endometrioid histology whereas type II is composed of high-grade histologies with more aggressive behaviour—ie, serous or clear-cell carcinomas.

At diagnosis, about three-quarters of women have disease confined to the uterine corpus. The standard definitive surgery includes total hysterectomy and bilateral salpingo-oophorectomy. Endometrial cancer spreads beyond the uterus by infiltrating directly through the myometrium and extending into the cervix. Metastasis is most often to the pelvic nodes and less frequently to the para-aortic nodes. Tumour type, grade, depth of myometrial invasion, and lymph-node status are key prognostic factors used to assess risk of recurrence and the need for adjuvant treatment.

The International Federation of Gynecology and Obstetrics (FIGO) classification of the stage of endometrial cancer requires pelvic and para-aortic lymphadenectomy.3 Lymphadenectomy for staging has prognostic importance, since patients who have no evidence of lymphatic involvement can forego further adjuvant therapy. It is unclear whether lymphadenectomy also has therapeutic benefit by the removal of malignant disease. The extent of benefit is counterbalanced by the surgical morbidity.

Adjuvant therapy for endometrial cancer can include systemic chemotherapy and pelvic and vault radiation. Recent randomised trials suggest that patients might have reduced morbidity with equivalent outcome by foregoing lymphadenectomy and adjuvant radiation.4, 5, 6 It is timely, therefore, to outline cancer-control strategies for low-resource countries where surgical or radiation support is limited.

With the burden of cancer in low-income and middle-income countries (LMCs) leading to increases in cancer-related morbidity, mortality, and economic cost, it is prudent to develop cancer-control strategies aimed at improving outcome while minimising toxicity and cost. Towards that goal, guidelines should encompass the entire management spectrum: from screening, primary prevention, and diagnosis at one end to palliative treatment of advanced endometrial cancer at the other end.

This article is a focused discussion of the above mentioned issues relevant to Asian countries and is not intended to be a systematic review of the management of endometrial cancer. The recommendations in this article are presented based on the framework formulated by the Breast Health Global Initiative,7 which developed an evidence-based process to create resource-sensitive guidelines for the management of breast cancer. This system recognises four levels of health-care resource availability: basic, limited, enhanced, and maximum (webpanel).

The recommendations in this article reflect the collective knowledge and opinion of a panel of Asian gynecological oncologists who convened at a workshop held at the Asian Oncology Summit in Singapore, April 5, 2009. Further details on the origin and running of the consensus workshop can be found in an accompanying comment.

Section snippets

Screening

There is no proven role for screening in asymptomatic women who have an average-risk or medium-risk of endometrial cancer—ie, those who are nulliparous, in late menopause, or have a history of unopposed oestrogen-replacement therapy or tamoxifen therapy. Screening should only be considered for high-risk women who might be carriers of the mutation associated with hereditary non-polyposis colonic cancer syndrome, or those with a suspected autosomal predisposition to colon cancer.8 These high-risk

Primary uterine surgery

Surgery is the cornerstone of therapy for endometrial cancer. Surgical staging recommended by FIGO includes peritoneal washing, extrafascial hysterectomy, bilateral salpingo-oophorectomy, and pelvic and para-aortic lymph-node dissection. Surgery could be done by laparotomy or a laparoscopic approach. The Gynecologic Oncology Group (GOG) assessed both procedures in patients with stage I–IIA endometrial cancer and found similar complications, longer operative times, shorter hospital stay, and

Surgical treatment

Pelvic exenteration has been used with a curative intent in selected patients with isolated central pelvic recurrences, especially after radiotherapy failure.60 When pelvic exenteration is not an option, cytoreductive surgery might have a role for selected patients with recurrent endometrial cancer.61 Optimum cytoreductive surgery, defined as no gross residual tumour or residual tumour less than 1–2 cm, could be achieved in about 65–75% of patients with recurrent disease. Longer survival with

Hormone replacement after cancer treatment

Data from several retrospective studies and one prospective case–control study showed that oestrogen therapy, with or without progestin, did not increase recurrence or mortality.66 However, these studies should be cautiously interpreted because of potential selection bias for inclusion of mainly low-risk patients. The only randomised double-blind trial, by the GOG, also showed similar outcomes for patients who did or did not have hormone replacement (relative risk 1·27; 80% CI 0·91–1·77).67

Surveillance after cancer treatment

The purpose for surveillance after cancer treatment is early detection of recurrence and to commence an appropriate treatment. In patients with endometrial cancer, there has been no standard recommendation for optimum follow-up and no randomised control trials showing a survival benefit for intensive follow-up. One systematic review found a 13% overall recurrence rate, but up to 60% of patients had distant metastasis so that early detection was unlikely to improve their survival.70 Most

Search strategy and selection criteria

References for this article were found through a search of Medline by use of the search terms: “uterine neoplasms”, “endometrial neoplasms”, and “cancer”. Only articles published in English, between January, 1970, and September, 2009, were included. Abstracts from annual academic meetings involving gynaecological cancer were included when relevant.

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