Treatment of recurrent or metastatic endometrial cancer

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Treatment of recurrent or metastatic endometrial cancer

Authors: Susana M Campos, MD, David E Cohn, MD

Section Editors: Barbara Goff, MD, Don S Dizon, MD, FACP

Deputy Editors: Sadhna R Vora, MD, Sandy J Falk, MD, FACOG

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Feb 2017. | This topic last updated: Jun 15, 2015.

INTRODUCTION — Adenocarcinomas of the endometrium are the most common gynecologic malignancy in

developed countries and the second most common in developing countries (cervical cancer is the most common

gynecologic malignancy in developing countries). Among the different histologic types of adenocarcinomas,

endometrioid uterine cancers have a more favorable prognosis and typically present at an early stage. Other

histologic types of uterine adenocarcinoma (eg, serous, clear cell) are associated with a poorer prognosis.

This topic will review the approach and treatment options for women with recurrent or metastatic endometrial

cancer. The initial treatment of low-risk, intermediate-risk, and high-risk endometrial cancers (which includes

women who present with locally advanced disease) are covered separately. In addition, chemotherapy protocols

used in the treatment of endometrial cancer is available separately.

CLINICAL PRESENTATION — Most women who relapse will do so within three years of the initial diagnosis.

Although the symptoms that herald recurrent or metastatic endometrial cancer are non-specific, most women will

have symptoms, with the most common consisting of bleeding (which emanates from the vagina, bladder, or

rectum), anorexia, weight loss, bone or pelvic pain, cough, shortness of breath, or lower abdominal or extremity

swelling [1].

However, recurrent endometrial cancer presents with different patterns, including disease localized to the vagina,

®

®

● (See "Approach to adjuvant treatment of endometrial cancer".)

● (See "Treatment of low-risk endometrial cancer".)

● (See "Adjuvant treatment of intermediate-risk endometrial cancer".)

● (See "Adjuvant treatment of high-risk endometrial cancers".)

● (See "Treatment protocols for gynecologic malignancies".)

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limited to the pelvis, or as metastatic disease involving the abdominal cavity or other organs. In addition, some

women may initially present with de novo metastatic disease (ie, stage IVB). For women suspected of recurrent

or metastatic disease, confirmation of this diagnosis is important, particularly if the diagnosis is being considered

for the first time.

DIAGNOSTIC EVALUATION — For women suspected of recurrent or metastatic endometrial cancer, the

diagnostic work-up should include the following:

Additional studies may include testing the tumor for estrogen (ER) and progesterone (PR) receptor expression,

especially in endometrioid cancer. In addition, overexpression of human epidermal growth factor 2 (HER2) is

performed at some centers, particularly in patients with uterine serous cancer.

OVERVIEW OF TREATMENT — Most women with a diagnosis of recurrent or metastatic disease have a poor

prognosis, regardless of treatment. In addition, unlike in the setting of a new diagnosis, data suggest that

histology does not predict treatment response in these patients. This was shown in a retrospective study of over

1200 women who participated in first-line chemotherapy trials (all of which tested an anthracycline-containing

combination) conducted by the Gynecologic Oncology Group (GOG) [2]. The main finding was that histologic

subtype did not predict response to first-line chemotherapy. However, specific histology subtypes were

associated with outcome:

Despite these data, it is still possible to cure selected patients with isolated disease with an aggressive local or

regional approach. Therefore, our approach to treatment varies by the clinical scenario:

● Pelvic examination with biopsies of areas suspected of recurrent disease

● Physical exam, with attention to nodal regions

Whole body imaging to evaluate for metastatic disease – Imaging of the chest, abdomen and pelvis can be

performed using computerized tomography (CT), magnetic resonance imaging (MRI), positron emissions

tomography (PET) scan, or a combined PET-CT scan. In general, computerized tomography (CT) is usually

the initial study. If CT results are equivocal, further evaluation using positron emissions tomography (PET)

scan or a combined PET-CT scan may be indicated. Ultimately, the choice between these imaging

modalities is dependent on institutional practice.

●

Measurement of cancer antigen 125 (CA-125) – Measurement of serum CA-125 may be useful in the

diagnostic work-up of a suspected recurrence, particularly in women that had an associated elevation in

their CA-125 at the initial diagnosis. However, the level of CA-125 alone should not influence treatment

decisions.

●

● Clear cell carcinoma was an independent predictor of poorer progression-free survival

● Serous and clear cell histologies were significant predictors of overall survival

Women with recurrent disease isolated to the vaginal vault are potentially curable. Choices for treatment

depend on whether radiation therapy (RT) was previously administered. (See 'Isolated vaginal recurrence'

below.)

●

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The posttreatment surveillance of women with endometrial cancer is discussed separately. (See "Overview of

endometrial carcinoma", section on 'Posttreatment surveillance'.)

ISOLATED VAGINAL RECURRENCE — Women who have undergone a hysterectomy for endometrial cancer

are at risk for a recurrence at the vaginal vault, although treatment with adjuvant radiation therapy (RT)

decreases this risk.

This was demonstrated in the Postoperative Radiation Therapy after Endometrial Cancer (PORTEC) randomized

trial that included 715 women with stage I endometrial cancer who underwent total hysterectomy and bilateral

salpingo-oophorectomy without lymphadenectomy, and were then assigned to adjuvant RT or no further

treatment [3]. Women treated with adjuvant RT had a lower incidence of vaginal recurrence at eight-year followup

(2 versus 8 percent), without a difference in overall survival. Further results of the PORTEC trial are discussed

separately.

For those who develop an isolated vaginal recurrence, the local treatment approach takes into account whether

or not prior RT was administered:

No prior radiation — For women with an isolated vaginal recurrence of endometrial cancer who were not

previously treated with RT, we suggest RT rather than surgery. However, surgery alone can be a curative and

reasonable alternative to RT in carefully selected patients, including those women who decline RT or are not

candidates for RT. (See 'Operative candidates' below.)

Radiation therapy — Data regarding treatment of an isolated vaginal recurrence are limited, but outcomes

appear favorable based on observational studies and the few studies of surgical treatment for this patient

population. Two retrospective case series (n = 50 and 69) evaluated women with endometrial cancer, nearly all of

whom had not received prior RT, following an isolated vaginal recurrence [3,4]. Treatment with RT was

associated with a five-year overall survival rate (OS) of 53 to 75 percent.

In addition, in the PORTEC I trial described above, 30 women who were not initially treated with RT had a

vaginal recurrence and were subsequently treated with curative intent; most received whole pelvic RT with or

without brachytherapy (28, although three women were treated with RT and surgery or RT and hormonal

therapy) [3]. The complete response rate for all women treated with curative intent was 87 percent.

The role of concurrent chemotherapy with RT is investigational and, in our practice, we do not offer combined

modality treatment. We encourage women in this situation to enroll in a randomized trial being conducted by the

Women with locally recurrent disease limited to the pelvis are also potentially curable. Treatment options

include surgery and/or RT, provided they are appropriate candidates for this. For women who are not

candidates for a local therapeutic approach, we proceed with medical treatment as we would for women with

metastatic disease. (See 'Recurrence limited to the pelvis' below and 'Patients who develop metastatic

disease' below.)

Women with disease outside of the pelvis either at their initial presentation or at the time of recurrence have

metastatic endometrial cancer. In most cases, treatment is not curative. Therefore, the approach should be

individualized. (See 'Metastatic disease' below.)

●