8 4 a Endometrial Cancer

8/13/2019 8 4 a Endometrial Cancer

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Epidemiology

Endometrial cancer (EC) remains the most

common gynecologic malignancy in the United

States.

The newly diagnosed EC increased in US from35,000 (1987) to 41,200 (2006)

The number of deaths rose from 2900 to 7350, a

153% increase


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Risk factors

postmenopausal status

body mass index (BMI) >25 kg/m2 or more

>30 pounds over ideal weight 3 x

>50 pounds over ideal weight 10 x

unopposed exogenous estrogen 9.5 x

nulliparous 2 x

late menopause 2.4 x

diabetes mellitus 2.8 x

hypertension 1.5 x

complex atypical hyperplasia 29 x

tamoxifen 3 x


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Risk reduction factors

normal weight

physically active

pregnancy

oral contraceptives 0.5 smoking decreases the risk of endometrial cancer

progestins even when administered in combination with

estrogen replacement.


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Epidemiology is important, however

only half of patients present with identifiable risk

factors.

The other half appear to be at low risk:

they are thin or of average weight,

have no history of exogenous estrogen exposure,

are perimenopausal (20%-25%),

or are younger than 40 years (5%).


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Diagnostic approach

Endometrial cancer presents with abnormal uterine

bleeding in 90% of patients Endometrial cancer is found in approximately 10% of patients with

postmenopausal bleeding (PMB).

Pap smear: 25% of patients with atypical endometrial cells on Pap smear havean underlying EC.

the presence of benign endometrial cells on Pap smear is

associated with EC in 6% of patients.

Abnormal endometrial thickness in TVUS (< 5mm, HRT < 7mm, tamoxifen < 8mm)

Karlsson B, Granberg S, Wikland M, et al. Transvaginal ultrasonography ofthe endometrium in women with postmenopausal bleedinga Nordicmulticenter study. Am J Obstet Gynecol. 1995;172(5):1488-1494


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Diagnosis

The criterion standard for EC diagnosis is dilation and

curettage, a procedure performed in the operating suite

with the patient under regional or general anesthesia


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Screening

Screening for EC using transvaginal ultrasonography in

asymptomatic postmenopausal women has a poor PPV

(9%) and is not recommended.

Langer RD, Pierce JJ, OHanlan KA, et al, Postmenopausal Estrogen/Progestin

Interventions Trial. Transvaginal ultrasonography compared with endometrial biopsy

for the detection of endometrial disease. N Engl J Med. 1997


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Treatment overview

The cornerstone of curative therapy for patients with EC issurgical treatment including complete hysterectomy, removal of remaining adnexal

structures, and appropriate surgical staging.

External pelvic radiotherapy and/or vaginal brachytherapy isused postoperatively for patients with tumor characteristicsthat predict: a high risk of local recurrence and a poor prognosis


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Treatment overview

A prospective GOG study showing a survival benefit forstage III or IV patients who received systemicchemotherapy vs those who received whole abdominalradiotherapy with a pelvic boost.

Palliative hormonal therapy or chemotherapy can beused in patients with liver and extra-abdominalmetastases

Primary external beam radiotherapy and/or intrauterinebrachytherapy can be used to treat medically inoperablepatients.


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Primary surgical treatment


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Survival is heavily dependent on

surgical stage


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Preoperative evaluation

Evaluation for systemic disease is typically limited to: physiacal exam transvaginal ultrasound

chest radiography

and laboratory evaluations performed in preparation for surgery.

Pelvic CT is of limited value and is indicated only whenthere is suspicion of extrapelvic disease. If imaging is necessary, such as for medically inoperable

patients, pelvic magnetic resonance imaging (MRI) is superior tocomputed tomography for visualizing the uterus and surrounding

tissues.

Baseline cancer antigen levels can be useful forpredicting extrauterine spread but are not sufficiently sensitive to replace surgical staging.


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Surgical treatment - lymphadenectomy

Pelvic and para-aortic lymph node dissection are crucial

to surgical staging for patients with EC

Lymphadenectomy is used as a:

staging,

therapeutic,

and diagnostic tool.


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Surgical treatment - lymphadenectomy

As a staging tool, it can be used to accurately define theextent of disease spread and determine the prognosis ofthe patient, thus facilitating comparative evaluations.

A therapeutic role for both pelvic and para-aorticlymphadenectomy has been suggested by retrospectiveinvestigations.

As a diagnostic tool, lymphadenectomy can be used todetermine the need for and extent of postoperativetreatment.


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New stage IA

New stage IB


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NCCN


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Case 1

She was admitted to hospital because newly diagnosedEC

Age 72

BMI 35.3 (156 cm/ 86 kg)

Hypertension from 10 years Diabetes from 1 year

Cholecystectomy 1998

Partial thyroidectomy 2000

Family history

Father: lung cancer

Mother sister: melanoma

abnormal uterine bleeding in April 2009 (after 24 years)

D & C Adenocarcinoma G1 (11.05.2009)


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Case 1

PE normal uterus

transvaginal us: small fibroids and endometrium 6mm

normal X-ray

abdominal US no changes abdominal CT not done


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Case 1

TAH, BSO, abdominal washing (16.06.2009)

No palpable nodes in pelvic and paraaortic area

Final histology:

Adenocarcinoma endometrioides endometrii G1 CIN1

Invasion in uterus less than of myometrium

Cancer in uterus less than 2 cm in diameter

Staging: pT1b / (old FIGO FIGO IB ) new FIGO IA


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FIGO

The published data suggest that adjuvant radiotherapy is

not indicated in the presence of low or intermediate risk

stage 1 disease. This would certainly include

a) all G1 tumours without serosal involvement, and G2 < 50%

myometrial invasion

Staging classifications and clinical practice guidelines of gynaecologic

cancers FIGO 2009


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NCCN


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PROTEC 1

Patients with EC FIGO I (grade 1 with deep [50%] myometrialinvasion, grade 2 with any invasion, or grade 3 with superficial[


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PROTEC 1

5-year locoregional recurrence rates were:

4% in the radiotherapy group vs 14% in the control group(p


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Case 1

Follow up without adjuvant radiotherapy


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Case 2

She was admitted to hospital because of abdominal pain

and abnormal endometrium in transvaginal us

(08.06.2009)

Age 51

2,0,0

BMI 21.9 (164 cm/ 59 kg)

Partial conisation of cervix 2005

Family history Father: panceratic cancer

Mother sister: genital cancer


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Case 2

PE normal

Transvaginal us:

abnormal uterus with endometrium 1,98 mm (last period in may

2009)

tumor in right side (3,78 x 2,78 cm)

normal X-ray

abdominal US no changes

abdominal CT no changes CA125 65,49 IU/ml


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Case 2 09-06-2009 D & C

Primary histology: Adenocarcinoma endometrioides endometrii

12-06-2009 open surgery:

Metastases tumors in all abdomen: left tube, right

ovary, omentum, on the liver, on surface of bowel TAH, BSO, OM, tumorectomy of all metastses

abdominal Residual 0 cm

Final histology:

Adenocarcinoma endometrioides endometrii G2 (superficialismyometrii)

Metastases in all biopsies

Staging: pT3b / FIGO IV B

ER 90% positive / PR 90% positive


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Case 2

Decision to start chemotherapy - AP


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Chemotherapy vs WAI Study compare:

whole-abdominal irradiation (WAI) and doxorubicin-cisplatin (AP)chemotherapy in women with stage III or IV EC (residual


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Chemotherapy vs WAI

Randall ME et al. JCO 2006


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Treatment failures

Most treatment failures in patients with EC are the resultof unrecognized occult extrauterine dissemination at thetime of primary treatment.

Traditional therapy (modality-based) for high-risk EC isexternal beam radiotherapy, frequently supplementedwith vaginal brachytherapy.

The modality-based approach improve local control butnot survival in early-stage disease


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Predictive factors The Mayo Clinic team has identified independent pathologic

risk factors predictive of the 4 routes of metastatic spread. Depth of myometrial invasion predicted hematogenous

dissemination;

positive lymph nodes and cervical stromal invasion predicted

lymphatic recurrence;

grade 3 histology or lymphovascular space involvement or bothwere correlated with vaginal recurrence;

stage IV disease or combinations of nonendometrioid histology,cervical stromal invasion, positive lymph nodes, and positiveperitoneal cytology were predictive of peritoneal failures

Mariani A, et all Hematogenous dissemination in corpus cancer. Gynecol Oncol. 2001

Mariani A, et all. Stage IIIC endometrioid corpus cancer includes distinct subgroups. GynecolOncol. 2002;.

Mariani A, Predictors of lymphatic failure in endometrial cancer. Gynecol Oncol. 2002

Mariani A, et all Predictors of vaginal relapse in stage I endometrial cancer. Gynecol Oncol.2005


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High-risk endometrial cancer

subgroups

Mariani A et all.

High-risk endometrial

cancer subgroups:

candidates for target-basedadjuvant

therapy.

Gynecol Oncol. 2004


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Disease-based therapy in

postoperatinve treatment of EC The presence of tumor characteristics predictive of

occult metastatic spread suggests the need to administerpostoperative therapy targeted at the site identified ashigh risk. patients at risk of vaginal recurrence - vaginal brachytherapy,

lymphati recurrence - external beam radiotherapy, hematogenous recurrence - systemic chemotherapy.

abdominal recurrence - systemic chemotherapy

Tumor characteristics predictive of multiple sites of

recurrence (eg, vaginal and hematogenous) should betargeted with multimodality therapy (eg, vaginalbrachytherapy and systemic chemotherapy).


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Old and new options

Mariani A et all.

High-risk endometrial cancer subgroups:

candidates for target-based adjuvant

th G l O l 2004

8 4 a Endometrial Cancer

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