2-medical treatment of endometrial hyperplasia and endometrial cancer

Medical Treatment ofEndometrial Hyperplasia

AndEndometrial Cancer

May /14/2015

Hatim Al-Dabbagh MBBS.FRCSC Gynecologic Oncologist

Dhahran Health CenterJohns Hopkins Aramco Healthcare

Endometrial Hyperplasia / Cancer –A disorder of the Glands

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


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

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%)

Endometrial Biopsy

Safe, relatively simple procedure useful in perimenopausal or high risk women

Not sensitive for detecting structural abnormalities (eg, polyps or fibroids)

Office-based techniques (gold standard replacing D&CDisposable devices (eg, Pipelle, Tis-u-Trap, Accurette, Z-

sampler)Reusable instruments (eg, Novak Curette, Randall

Curette, Vabra Aspirator)

Presenter

Presentation Notes

Endometrial biopsy is a safe, relatively simple procedure that can be performed during the initial office visit. It is widely used for excluding endometrial cancer, especially in peri- and postmenopausal women. A biopsy may also be used to determine if the bleeding is ovulatory or anovulatory. A drawback to the utility of endometrial biopsy is that it is not a sensitive technique for detecting structural abnormalities, such as polyps or fibroids. Several techniques may be used to obtain endometrial samples. Unfortunately, hospital-based D&C is still performed—even though it should be discouraged. It is no longer considered the gold standard for evaluation of abnormal bleeding, except in patients who have had a miscarriage. A diagnostic D&C is highly inaccurate, resulting in missed diagnoses and incomplete removal of intracavitary pathologic tissue, and is associated with a high false-negative rate. A recently reported retrospective study demonstrated that D&C failed to detect intrauterine disorders in 248 of 397 (62.5%) women. Office-based sampling techniques have been shown to be at least equivalent to D&C in sensitivity and rate of positive diagnosis/effectiveness, while being less intrusive and more cost-effective. Several sampling devices are available for office-based endometrial biopsy, including disposable devices (eg, Pipelle, Tis-u-Trap, Accurette, Z-sampler) and reusable instruments (eg, Novak Curette, Randall Curette, Vabra Aspirator).

Possible Endometrial Biopsy Findings

Proliferative, secretory, benign, or atrophic endometrium

Inactive endometriumTissue insufficient for analysisNo endometrial tissue seenSimple or complex (adenomatous) hyperplasia

without atypiaSimple or complex (adenomatous) hyperplasia with

atypiaEndometrial adenocarcinoma

Presenter

Presentation Notes

The results of most endometrial biopsies fall into one of several categories, shown on this slide. Atypia is the most important risk factor for endometrial cancer. Approximately 25% of patients with atypia have been reported to develop endometrial cancer, compared with only 2% of patients without atypia. A finding on biopsy of normal secretory endometrium indicates that the patient is having ovulatory cycles, and abnormal uterine bleeding is therefore most likely due to a cause other than anovulation.

SUMMARY AND RECOMMENDATIONS

Hysterectomy is the treatment of choice for women with endometrial hyperplasia with atypia who are not planning future pregnancy.For postmenopausal women with atypical hyperplasia, Hysterectomy with concomitant bilateral salpingo-oophorectomy (BSO) rather than hysterectomy alone is the right choice.For premenopausal women undergoing treatment with hysterectomy, BSO remains controversial.

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Progestin therapy is an option for women with atypical endometrial hyperplasia who wish to preserve fertility or who cannot tolerate surgery. Oral Megestrol acetate 80 mg twice per day every day. This may be increased to 160 mg twice per day if there is no regression of the hyperplasia on follow-up endometrial sampling.

Approximately 35 percent of women will fail conservative management.

Progestins rather than surgery for treatment of endometrial hyperplasia without atypia is the rigt choice.

Medroxyprogesterone acetate 10 mg daily for three to six months. Other progestin preparations may also be used. Observation with follow-up sampling, especially for simple hyperplasia without atypia, is also reasonable, especially in patients who cannot tolerate progestin therapy

Endometrial Cancer – “The Usual Suspects”

Endometrial Carcinomas

• Make up more than 95% of uterine cancers

• Most common invasive gynecologic malignancy

Endometrial Carcinoma

• Stereotyped as a disease of the obese patient and the disease usually proceeds through a precursor of endometrial hyperplasia

• Such tumors have endometrioid histology and are usually of early stage and low grade

Endometrial Carcinoma

• However, such a stereotype does not account for many endometrial cancers

• Nonendometrioid histologies include papillary serous & clear cell carcinomas

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

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

Endometrial Carcinoma -Natural History

• Most common route of spread is direct penetration of the myometrium and direct extension into the cervix and endocervix; tumor may also gain access to lymphatic spaces resulting in nodal metastases

• Endometrial cancers may spread to pelvic lymph nodes, as well as the paraaortic chain

Endometrial Carcinoma -Natural History

• The occasional presence of malignant cells in peritoneal washings demonstrates the potential for transtubal migration of disease

• Hematogenous spread can result in distant disease

• Tumors with clear cell & papillary serous histology are biologically more aggressive than typical endometrioid carcinomas

Endometrial Carcinoma -Staging

• Staging of endometrial cancer is surgical • Grade is assessed by the percentage of

solid growth pattern

Endometrial Carcinoma -Grading

• G1 = <5% of a nonmorular, solid growth pattern

• G2 = 6% to 50% of a nonmorular, solid growth pattern

• G3 = > 50% of a nonmorular, solid growth pattern

Endometrial Carcinoma -Grading

• Papillary serous, clear cell and adenosquamous carcinomas are graded according to the nuclear grade of the glandular component

Staging of Corpus Cancer

• Stage IA Tumor limited to Endometrium or Invasion to < 1/2 of myometrium

• Stage IB Invasion of > 1/2 of myometrium, but not to serosa


• Stage II Cervical stromal invasion


• Stage IIIA Tumor invades serosa, and/or adnexa, and/or + peritoneal cytology

• Stage IIIB Vaginal metastases


• Stage IVA Tumor invasion of bladder and/or rectal mucosa

• Stage IVB Distant metastases -intraabdominal contents or inguinal nodes

Carcinoma of Endometrium -Stage Distribution

• Stage I - 72.8%• Stage II - 10.9%• Stage III - 13.2% • Stage IV - 3.1%

– J Epidemiol Biostat 3:35, 1998

Endometrial Carcinoma -Treatment

• The cornerstone of treatment is total abdominal hysterectomy and bilateral salpingo-oophorectomy

• This operation should be performed whenever possible

• Some patients require sampling of the regional (pelvic & paraaortic) lymph nodes as based on the pathologic information available

Endometrial Carcinoma -Treatment

• Patients with stage III and IV disease require individualization as to therapy -this often involves radiotherapy and surgery in selected cases

Endometrial Carcinoma -Prognostic Factors

• Tumor Stage• Grade/Histologic type• Depth of Invasion• Peritoneal cytologies• Receptor status (ER/PR)• Patient age• Vascular space invasion• DNA Ploidy

Follow-up of Affected Patients

• Patients seen every 3-4 months for first two years

• Seen every 6 months thereafter until 5 years after treatment

• Seen yearly thereafter• Majority of recurrences found by

symptoms, exam, CXR and Pap smear

Recurrent Disease

• Approximately three quarters of patients who experience recurrence will do so in the first three years after primary therapy

• Isolated vaginal metastases are the most amenable to therapy

• Patients with vaginal metastases should be evaluated to rule out further metastatic spread

Thank You

2-medical treatment of endometrial hyperplasia and endometrial cancer

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