Endometrial Cancer

Endometrial cancer is the most common cancer of the female genital tract and the fourth most common cause of cancer overall in women. 3% of women will develop endometrial cancer in their lifetime. 75% of endometrial cancers are adenocarcinomas (arising from endometrial hyperplasia caused by a hyperestrogenic environment). The incidence is higher in white women, but black women have a higher mortality

The most common presentation of endometrial carcinoma is abnormal uterine bleeding (post-menopausal bleeding)

Risk factors for endometrial carcinoma
- Hyperestrogenism
  - High-dose menopausal estrogen (10-20x RR)
  - Obesity (2-4x)
  - Nulliparity (2x)
  - Early menarche
  - Late menopause (2x)
  - Use of tamoxifen (2-3x)
  - PCOS (3x)
- Medical conditions
  - T2DM (2x)
  - Hypertension
  - Gallbladder disease
  - Lynch syndrome (22-50% lifetime risk)
- Higher SES (1.5-2x)
- Older age
- Living in North America or Northern Europe (3-18x)
Histologic variants of endometrial cancer
- Endometrial adenocarcinoma (75%) – most common
- Serous carcinoma (5-10%) – some are HER2/Neu positive, studies are underway for using Trastuzumab
- Clear cell carcinoma (<5%)
- Mucinous carcinoma (1-2%)
- Mixed type (10%)
- Undifferentiated (rare)
- Squamous cell carcinoma (extremely rare)

	Type I	Type II
Unopposed estrogen	Present	Absent
Estrogen responsive	Yes	No
Rate of growth	Slow	Rapid
Precursor lesion	Atypical hyperplasia	Atrophic epithelium, Endometrial intraepithelial carcinoma
Histology	Endometrioid	Serous, clear cell
Grade	Low	High
Depth of invasion	Superficial	Deep
Age at diagnosis	Younger	Older
Prognosis	Better	Worse
Genetic changes	PTEN, KRAS	p53, HER2/Neu (serous)

Patient History
- Use of post-menopausal estrogen supplements
- Use of Tamoxifen
- Nulliparity
- Early onset of menarche and Late menopause
- Family History of malignancies (Lynch syndrome etc.)
- Ensure that pap smear is up to date
Signs and Symptoms
- Abnormal uterine bleeding
  - Post-menopausal women: Post-menopausal bleeding
  - Pre-menopausal women: Menorrhagia, Intermenstrual spotting
Physical Exam
- Pelvic exam (bimanual and speculum): feel for masses (fibroid, polyps, ovarian tumours), exclude lacerations, foreign bodies, cervical cancer
Investigations
- Confirm diagnosis
  - Transvaginal ultrasound
    - Thickened endometrial stripe
  - Endometrial biopsy: for postmenopausal women and premenopausal women with risk factors for endometrial cancer
- Labs
  - Qualitative hCG
  - CBC
  - TFTs
- Staging
  - Total Abdominal Hysterectomy + Bilateral Salpingoophorectomy (TAH + BSO)
  - Peritoneal washings
  - Pelvic and Para-aortic lymphadenectomy
- Metastasis
  - CXR
  - LFTs
- Prognosis and response to treatment
  - CA-125 levels
Treatment
- TAH + BSO
- Further treatment
  - Stage I: None
  - Stage II: Radiation (controversial)
  - Stage III and IV: chemotherapy and radiation
    - TAP (Paclitaxel, Adriamycin, Cisplatin)

Staging of endometrial carcinoma

Stage	Description	% at diagnosis	5-year survival
Stage I	Tumor confined to the corpus uterus (endometrium and myometrium)	75%
IA	< 50% myometrial invasion		88-91%
IB	≥ 50% myometrial invasion		75-88%
Stage II	Tumor invades cervical stroma but does not extend beyond the uterus	25%	67-77%
Stage III	Local and/or regional spread of the tumor
IIIA	Invades the serosa, adnexae, or peritoneum		58-60%
IIIB	Vaginal and/or parametrial involvement		41-50%
IIIC	Metastasis to pelvic or para-aortic nodes		32-47%
Stage IV	Metastasis to bowel, bladder, or beyon
IVA	Metastasis to bowel or bladder mucosa		17-20%
IVB	Distant metastasis including abdominal structures and/or inguinal nodes		5-15%