Endometrial Cancer; Evidence Based Approach

Endometrial Endometrial CancerCancerPresented byPresented by

Dr/ Ahmed Walid AnwarDr/ Ahmed Walid AnwarAssistant professor of Obs & Gyn Assistant professor of Obs & Gyn

Benha Faculty of MedicineBenha Faculty of Medicine

Endometrial cancer

– The most common ♀ pelvic genital cancer .

– The life time risk of developing endometrial Ca is 2.4% in white women & 1.3% in black (In USA).

– Age: Peak incidence in the 6th & 7th decade of life (disease of

postmenopausal women). Only 2-5% occur before 40 years.

– Higher survival rate due to early diagnosis ( 75% diagnosed in Stage I).

– Estrogen has been implicated as a causative factor.

These risk factors are only helpful in identifying women at risk for type I disease.

Risk factors for endometrial cancer OLD AUNT

O=Obesity

L=Late menopause

D=Diabetes mellitus

A=cAncer: ovarian, breast, colon

U=Unopposed estrogen: PCOS, anovulation, HRT

N=Nulliparity

T=Tamoxifen, chronic use

Causes of high unopposed estrogen Exogenous Estrogen: Estrogen Replacement

Therapy in postmenopausal women. Endogenous Estrogen:

– Increased secretion : e.g. feminizing ovarian tumors (granulose cell tumor).

– Increased androgen precursors: e.g. androgen secreting tumors, liver diseases, chronic an-ovulation (PCOS), or stress.

– Increased aromatization: e.g. obesity, liver diseases, or hyperthyroidism.

– Increased free estrogen due to decreased level of SHBG.

Protective Factors1. Oral contraceptives: Protective effect probably due to progesterone

Decreases both the risk of ovarian and endometrial cancer (RR = 0.6 if

used for one year…effect lasts for 15 years!)

1. Physical activity

2. Pregnancy and breast-feeding :The risk may be lower in women with a

higher number of pregnancies and who breast-feed for more than 18 months.

3. Diet: low in saturated fats and high in fruits and vegetables and soy -based foods as

a regular part of the diet may lower the risk of endometrial cancer.

4. Smoking

Other Types of Uterine CancerOther Types of Uterine Cancer LeiomyosarcomaLeiomyosarcoma

– Rapidly growing fibroid should be evaluated Rapidly growing fibroid should be evaluated Stromal sarcomaStromal sarcoma Carcinosarcoma (MMMT)Carcinosarcoma (MMMT)

leiomyosarcoma

MMMT

Spread PatternsSpread Patterns Direct extension Direct extension

– most commonmost common Transtubal Transtubal LymphaticLymphatic

– Pelvic usually first, then para-aorticPelvic usually first, then para-aortic HematogenousHematogenous

– Lung most commonLung most common– Liver, brain, boneLiver, brain, bone

Endometrial hyperplasia

Endometrial Intraepithelial Neoplasia (EIN) system

Def: EIN is a histopathological presentation of premalignant

endometrial disease which elevated the risk of {endometrioid

(Type I) endometrial adenocarcinoma}.

Significance:

– Women with endometrial hyperplasia subdivided into EIN

versus non-EIN categories.

– Progression to cancer more than one year following

EIN diagnosis is 45 times more likely compared to

women without EIN.

RepresentationRepresentation Asymptomatic : Endometrial cells on PapAsymptomatic : Endometrial cells on Pap BB: : The “classic symptom” is abnormal uterine Bleeding

20-30% of women with post-menopausal bleeding will have uterine cancer.

( the risk is higher the farther they are away from menopause)

CC DD EE P (Pain, Pressure)P (Pain, Pressure) MetastasisMetastasis

Diagnostic evaluation Outpatient endometrial biopsy with the Pipelle catheter is

reliable and accurate for the detection of disease in most cases of

endometrial cancer (level of evidence: A).

Detection rates by pipelle was :Detection rates by pipelle was :

– 91 and 99% for endometrial ca. 91 and 99% for endometrial ca.

– 81% for hyperplasia was81% for hyperplasia was

Hysteroscopic-guided endometrial biopsy remains the gold

standard for endometrial cancer diagnosis (level of evidence:

A ).

Diagnostic evaluation

Transvaginal ultrasonography is highly sensitive

and specific in predicting the presence of endometrial

cancer and can be used to select patients for

endometrial biopsy (level of evidence: B).

If symptomatology persists despite negative findings

from the previously cited tests, further evaluation is

justified because none of these tests have 100%

sensitivity (level of evidence: B).

Metastatic evaluation

Routine preoperative assessment of endometrial cancer

patients with imaging tests evaluating for metastasis is not

necessary as it is surgically staged disease (level of evidence:

A).

Serum CA125 measurement may be useful in management

planning of selected endometrial cancer patients but cannot

currently be recommended for routine clinical use (level of

evidence: C).

Treatment

Treatment of endometrial hyperplasia .

Treatment of endometrial cancer.

Treatment of Treatment of endometrial cancer

Approach to endometrial cancer: best practices

The initial management of endometrial cancer should include

total hysterectomy, bilateral salpingo-oophorectomy, and

pelvic and para-aortic lymphadenectomy. Exceptions to this

approach should be made only after consultation with a

gynecologic oncologist (level of evidence: A).

Laparoscopy should be embraced as the standard surgical

approach for comprehensive surgical staging in women with

endometrial cancer (level of evidence: A).

Approach to endometrial cancer: best practices

Vaginal hysterectomy may be an appropriate

treatment in select patients who are at high risk

for surgical morbidity (level of evidence: C).

Robotic-assisted laparoscopic staging is feasible

and safe in women with endometrial cancer (level

of evidence: B).

Role of lymphadenectomy

Patients with grade 1–2 endometrioid tumors, less than 50%myometrium invasion, and tumor of 2 cm or less seem to be at low risk for recurrence and may not require a surgical lymphadenectomy (level of evidence: B).

Lymphadenectomy may alter or eliminate the need for adjuvant therapy and its associated morbidity (level of evidence: B).

Sentinel lymph node dissection may reduce the morbidity associated with standard lymphadenectomy and may enhance the therapeutic benefit of surgical staging in early endometrial cancer (level of evidence: I).

Surgical approach for advanced endometrial cancer

Aggressive surgical cytoreduction improves progression-free and overall survival in patients with advanced or recurrent endometrial cancer (level of evidence: C).

Exenteration offers the only curative option in patients with recurrent endometrial cancer who have received previous irradiation (level of evidence: C).

Adjuvant Therapy inEndometrial Cancer

Stage I Intermediate-Risk Endometrial Cancers

External beam pelvic radiotherapy

– 1. Pelvic radiation has been shown to reduce local

recurrence in low to intermediate-risk endometrial

carcinoma. (II-1)

– 2. Pelvic radiation has been shown to reduce local

pelvic and vaginal recurrences in intermediate- to

high-risk endometrial carcinoma. (II-1)

Stage I Intermediate-Risk Endometrial Cancers

Vaginal brachytherapy

– 3. Vaginal brachytherapy alone in the treatment of women with

intermediate- to high-risk endometrial cancer has been shown to have

outcomes in local control and overall survival that are similar to those

of pelvic radiotherapy in a well-defined intermediate- to high-risk

group. (I)

– 4. Vaginal brachytherapy has the same outcome as external beam

radiotherapy with respect to overall survival in the defined

intermediate- to high-risk group. (I)

Stage I Intermediate-Risk Endometrial Cancers

Chemotherapy– 5. Chemotherapy has not been well studied in

stage I intermediateto high-risk endometrial cancers. There is no strong evidence for or against chemotherapy in this population at present. The benefits of chemotherapy in addition to adjuvant radiotherapy specifically in surgically stage I patients with high-risk features are not clearly defined. (III)

Stage I Intermediate-Risk Endometrial Cancers

Expectant Management– 6. Patients in the intermediate-risk category who

are managed expectantly have a higher recurrence

rate than those who are treated, although there has

not been a lack of survival benefit demonstrated.

Patients who are managed expectantly report

higher scores in quality of life studies because of

less gastrointestinal toxicity. (II-3)

Advanced Stage (II to IV) Endometrial Cancer

– 7. Chemotherapy with cisplatin and doxorubicin

or carboplatin and paclitaxel has demonstrated

efficacy in advanced uterine cancer in published

phase III studies. (II-2)

Five Year SurvivalFive Year Survival

72%72% diagnosed at this stage I, diagnosed at this stage I, 3%3% Diagnosed at stage IV Diagnosed at stage IV

Conclusions

Endometrial carcinoma is the commonest female

genital tract cancer.

Routine screening for EC is not recommended.

However annual screening is recommended in

women at risk for hereditary nonpolyposis colorectal

cancer.

Endometrial carcinoma is a surgically staged disease.

Conclusions

The initial management of endometrial cancer should include total hysterectomy, bilateral salpingo-oophorectomy, and pelvic and para-aortic lymphadenectomy.

Primary radiotherapy or hormonal treatment may be recommmended in special situations.

Adjuvant radiotherapy and /or chemotherapy are recommended in patients with high risk for recurrence.

Conclusions

Endometrial carcinoma has the best prognosis

due to early presentation (PMB).

Disease stage is the most predictive factor for

survival.

Lymph node metastasis is the most predictive

factor for survival in early stage endometrial

carcinoma.