Endometrial Cancer

Kristin Janson Redmond and Fariba Asrari

Background

What is the incidence of endometrial cancer in the U.S.?

Endometrial cancer is the most common gyn malignancy in the U.S., with an incidence of ~44,000 cases/yr annually. It is the 2^nd most common cause of gyn cancer deaths.

What are the 2 forms of endometrial cancer?

Forms of endometrial cancer:

Type I: endometrioid, 70%–80% of cases, estrogen related
Type II: nonendometrioid, typically papillary serous or clear cell, high grade, not estrogen related, aggressive clinical course

What are the risk factors for endometrial cancer?

Risk factors for endometrial cancer:

Exogenous unopposed estrogen
Endogenous estrogen (obesity, functional ovarian tumors, late menopause, nulliparity, chronic anovulation/polycystic ovarian syndrome)
Tamoxifen
Advancing age (75% postmenopausal)
Hereditary (HNPCC)
Family Hx
HTN

What are protective factors for endometrial cancer?

Protective factors for endometrial cancer include combination oral contraceptives and physical activity.

What is the most common clinical presentation of endometrial cancer?

Endometrial cancer presents with abnl vaginal bleeding in 90% cases.

What % of post-menopausal women with abnl vaginal bleeding have endometrial cancer?

Only 5%–20% of postmenopausal women with abnl vaginal bleeding have endometrial cancer.

What are the 3 layers of the uterine wall?

The 3 layers of the uterine wall are the endometrium, myometrium, and serosa.

What is the primary lymphatic drainage of the uterus?

The primary lymphatic drainage of the uterus is to the pelvic LNs (parametrial, internal and external iliacs, obturator, common iliac, presacral). Also, direct spread to the para-aortic (P-A) nodes (from the fundus) can occur.

What % of endometrial cancer pts with positive pelvic LNs also will harbor Dz in the P-A LNs? What is the chance of P-A nodal involvement if pelvic nodes are negative?

~33% of pts with pelvic LN involvement also have involvement of the P-A nodes. Isolated P-A nodal mets in the setting of negative pelvic nodes occur in ~1% of surgically staged endometrial cancer cases. This low rate seems consistent for low- and high-grade lesions.

What determines the grade of endometrial tumors?

The grade of endometrial tumors depends on the glandular component:

Grade I: ≤5% nonsquamous solid growth pattern
Grade II: 6%–50% nonsquamous solid growth pattern
Grade III: >50% nonsquamous solid growth pattern

What is the risk of LN involvement by DOI and grade per GOG 33?

According to GOG 33, the risk of LN involvement is <5% for tumors limited to the endometrium (all grades) and 5%–10% for tumors invading the inner and middle 3^rd of the myometrium (all grades). For tumors invading the outer 3^rd of the myometrium, the risk is approximately 10% for grade 1, 20% for grade 2, and 30% for grade 3. (Creasman WT et al., Cancer 1987)

What are the most aggressive histologies of endometrial cancer?

The most aggressive histologies of endometrial cancer are papillary serous, clear cell, and pure squamous cell.

What % of endometrial cancers are adenocarcinoma?

75%–80% of endometrial cancers are adenocarcinomas.

According to the American College of Obstetricians and Gynecologists (ACOG), how should women be screened for endometrial cancer?

According to the ACOG, there is no appropriate cost-effective screening test for endometrial cancer.

Workup/Staging

Per the NCCN, what is the workup for endometrial cancer?

NCCN endometrial cancer workup: CBC, PAP smear, endometrial Bx, and CXR. If extrauterine Dz is suspected, consider CA 125, MRI/CT, cystoscopy, and sigmoidoscopy.

What are the sensitivity and specificity of an endometrial Bx?

Endometrial Bx has 90%–98% sensitivity and 85% specificity.

When is D&C recommended?

D&C is recommended if endometrial Bx is nondiagnostic.

What is involved in the surgical staging of pts with endometrial carcinoma?

Surgical staging for endometrial cancer:

Vertical incision
Peritoneal washing/cytology (controversial)
Exploration of all peritoneal surfaces with Bx of any lesions
Total abdominal hysterectomy (TAH)/bilateral salpingo-oopherectomy (BSO)
Uterus bivalved in operating room
Omental Bx (omentectomy for uterine papillary serous carcinoma [UPSC]/clear cell carcinoma [CCC])
Pelvic/P-A LN sampling vs. dissection

During the surgical staging procedure for endometrial cancer, what features are an indication for P-A nodal sampling? Approximately what % of pts have these features?

PA sampling should take place in endometrial cancer pts with the following:

Gross P-A Dz
Positive pelvic LN
Gross adnexal mass
More than one third myometrial involvement

~25% of pts have these features, but they account for 98% of all positive P-A LNs.

Per the NCCN, when is cystoscopy or sigmoidoscopy indicated?

Per the NCCN, cystoscopy or sigmoidoscopy are indicated only for Sx or advanced lesions.

What is the AJCC 7^th edition (2009)/FIGO (2008) pathologic staging for endometrial cancer?

Stage T1a/IA: limited to endometrium or less than one half of myometrium
Stage T1b/IB: invades half or more of myometrium

Note: Endocervical glandular involvement only is considered AJCC T1 and FIGO stage I.

Stage T2/II: invades connective tissue of cervix but does not extend beyond uterus
Stage T3a/IIIA: tumor involves serosa and/or adnexa by direct extension of mets
Stage T3b/IIIB: vaginal involvement or parametrial involvement
Stage T4/IVA: tumor invades bladder mucosa (bullous edema is not sufficient) and/or bowel mucosa
Stage N0: no regional LN mets
Stage N1/IIIC1: regional LN mets to pelvic nodes
Stage N2/IIIC2: regional LN mets to P-A nodes
Stage M1/IVB: DMs