Uterine Cancers A. Alobaid, MBBS, FRCS(C), FACOG Consultant, Gynecologic Oncology Assistant professor, KSU Medical Director, Women’s Specialized Hospital King Fahad Medical City

Introduction It is the most common malignancy of the female genital tract 2-3% of women will develop endometrial cancer during their lifetime Endometrial cancer is a disease that occurs primarily in postmenopausal women

Epidemiology The median age of adenocarcinoma of the uterine corpus is 61 years 20-25% of the patients will be diagnosed before the menopause

Risk Factors Nulliparity Late menopause Obesity Anovulatory cycles, polycystic ovary syndrome Unopposed estrogen exposure Tamoxifen Diabetes mellitus, hypertension

Risk Factors Women who used oral contraceptives at some time, had a 0.5 relative-risk of developing endometrial cancer compared with women who had never used oral contraceptives Cigarette smoking apparently decreases the risk for development of endometrial cancer

Tamoxifen The relative risk of endometrial cancer in women taking tamoxifen in the adjuvant setting was 2.2 Tamoxifen causes subepithelial stromal hypertrophy which cause the endometrial stripe to be thickened on sonography Current consensus opinion recommends annual pap smears for women taking tamoxifen, and endometrial biopsy only for women with abnormal vaginal bleeding

Endometrial Hyperplasia It represents a spectrum of morphologic and biologic alterations of the endometrial glands and stroma, ranging from an exaggerated physiologic state to carcinoma in situ It results from protracted estrogen stimulation in the absence of progestin influence

Endometrial Hyperplasia

The risk of endometrial hyperplasia progressing to carcinoma is related to the presence and severity of cytologic atypia Progestin therapy is very effective in reversing endometrial hyperplasia without atypia but is less effective for endometrial hyperplasia with atypia

Symptoms of Endometrial Cancer 90% of women have vaginal bleeding or discharge as their only presenting complaint Less than 5% of women diagnosed with endometrial cancer are asymptomatic

Postmenopausal Bleeding

60-80% of patients with postmenopausal bleeding have endometrial atrophy Only about 10% of the patients have endometrial cancer The older the patient is, the greater the risk of cancer

Diagnosis Office endometrial aspiration is the first step in evaluating a patient with abnormal uterine bleeding The diagnostic accuracy of office-based endometrial biopsy is 98% A critical review of 33 reports of 13,598 D&Cs and 5851 office biopsies showed that D&C had a higher complication rate than office biopsy but that the adequacy of the specimens was comparable

Diagnosis If the initial biopsy result is negative, further evaluation is recommended in patients with persistent symptoms, due to the high risk (11%) of an existing lesion having been overlooked Feldman S, gynecol Oncol, 1994;55:56-9

Diagnosis Endometrial thickness of less than 4mm as measured by ultrasonography is highly suggestive of endometrial atrophy (sensitivity 96-98%, specificity 36-68%, false negative rate 0.2%)

Pathology There appear to be two different pathogenetic types of endometrial cancer The most common type occur in younger perimenopausal women with a history of exposure to unopposed estrogen These estrogen-dependent tumors tend to be better differentiated and have a more favorable prognosis The other type occur in older, thin women with no source of estrogen stimulation

Pathology

Prognostic Factors

Treatment Exploratory lapratomy, peritoneal washing (cytology), total abdominal hysterectomy and bilateral salpingo- oopherectomy are the primary operative procedures for carcinoma of the endometrium

Treatment

Patients with stage I grade 1 and 2 tumors without myometrial invasion (stages IA, G1, G2) have an excellent prognosis and require no postoperative therapy Patients with stages IC or IA/IB G3 are given postoperative vaginal cuff irradiation

Treatment Patients with stage II are treated similar to patients with cervical cancer, the options are: Wertheim radical hysterectomy with BSO, bilateral pelvic lymphadenectomy and selective aortic node dissection, extrafascial TAHBSO followed by adjuvant whole pelvis radiation therapy, or with whole-pelvis radiation therapy, followed by TAHBSO and selective para-aortic lymphadenectomy

Treatment Patients with stage III after a thorough surgical staging are treated with postoperative adjuvant pelvic radiation therapy Patients with stage IV are usually most suitable for systemic hormonal therapy or chemotherapy and possible local radiation

Follow-up Patients are followed up in the first two years every 3-4 months, thereafter the patients are followed every 6 months for the following three years After 5 years of remission, the follow-up will be annual

Recurrence In the early stage disease treated by surgery only, recurrences are usually local/pelvic Local recurrences are preferably managed by radiation, surgery, or a combination of the two Patients with non-localized recurrences are treated with hormonal therapy or chemotherapy

Sarcomas Sarcomas of the uterus are rare, and carry a poor prognosis 2-6% of uterine cancers. The incidence appears to be changing, increasing recently, part of this may be due to better recognition by pathologists. Some of this increase, also, can be attributable to the greater use of pelvic radiation therapy.

Classification These tumors arise either from the endometrium: MMMT (carcinosarcoma) = 50% ESS = 8-10% Or from the myometrium: LMS = 40%

Sarcomas MMT (Mixed Mullerian tumors): also they are called carcinosarcomas Currently they are classifiedand and treated as poorly differentiated adenocarcinomas Outcome is generally poor

Leiomyosarcomas (LMS) They arise from either the myomertrium itself or the smooth muscle of the myometrial veins. Most cases are diagnosed incidentally while performing surgery to fibroids There is scant evidence in the literature to support the common teaching that rapid uterine enlargement heralds the onset of LMS.

Leiomyosarcomas (LMS) Treatment is surgical The spread of LMS is hematogenous, so most recurrences are in distant sites Chemotherapy is reserved for patients with advanced or recurrent disease The 3-year progression-free survival for stage I and II patients is 21-31%

Endometrial Stromal Sarcomas LG ESS in premenopausal women. progress slowly with an indolent clinical course. long term survival is the role. 5 years survival is %, but about 37-60% will eventually recur after a very long time.

HG ESS In postmenopausal women. More aggressive behavior, frequent and early recurrence. 5 year survival is 25-55%, median time to recurrence was 7 months

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