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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