EndometrialEndometrial
CancerCancer
Presented byPresented by
Dr/ Ahmed Walid AnwarDr/ Ahmed Walid Anwar
Assistant professor of Obs & GynAssistant 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 Factors
1. 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 evaluatedRapidly growing fibroid should be evaluated
 Stromal sarcomaStromal sarcoma
 Carcinosarcoma (MMMT)Carcinosarcoma (MMMT)
leiomyosarcom
a
MMMT
Spread PatternsSpread Patterns
 Direct extensionDirect extension
– most commonmost common
 TranstubalTranstubal
 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 ofTreatment 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 in
Endometrial 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 IVDiagnosed 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.
Endometrial Cancer; Evidence Based Approach

Endometrial Cancer; Evidence Based Approach

  • 1.
    EndometrialEndometrial CancerCancer Presented byPresented by Dr/Ahmed Walid AnwarDr/ Ahmed Walid Anwar Assistant professor of Obs & GynAssistant professor of Obs & Gyn Benha Faculty of MedicineBenha Faculty of Medicine
  • 2.
    Endometrial cancer – Themost 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.
  • 3.
    These risk factorsare only helpful in identifying women at risk for type I disease.
  • 4.
    Risk factors forendometrial 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
  • 5.
    Causes of highunopposed 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.
  • 6.
    Protective Factors 1. Oralcontraceptives: 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
  • 8.
    Other Types ofUterine CancerOther Types of Uterine Cancer  LeiomyosarcomaLeiomyosarcoma – Rapidly growing fibroid should be evaluatedRapidly growing fibroid should be evaluated  Stromal sarcomaStromal sarcoma  Carcinosarcoma (MMMT)Carcinosarcoma (MMMT) leiomyosarcom a MMMT
  • 9.
    Spread PatternsSpread Patterns Direct extensionDirect extension – most commonmost common  TranstubalTranstubal  LymphaticLymphatic – Pelvic usually first, then para-aorticPelvic usually first, then para-aortic  HematogenousHematogenous – Lung most commonLung most common – Liver, brain, boneLiver, brain, bone
  • 10.
  • 12.
    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.
  • 14.
    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
  • 18.
    Diagnostic evaluation  Outpatientendometrial 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 ).
  • 19.
    Diagnostic evaluation  Transvaginalultrasonography 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).
  • 20.
    Metastatic evaluation  Routinepreoperative 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).
  • 23.
    Treatment  Treatment ofendometrial hyperplasia.  Treatment of endometrial cancer.
  • 26.
    Treatment ofTreatment ofendometrial cancer
  • 27.
    Approach to endometrialcancer: 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).
  • 28.
    Approach to endometrialcancer: 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).
  • 29.
    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).
  • 30.
    Surgical approach for advancedendometrial 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).
  • 33.
  • 35.
    Stage I Intermediate-Risk EndometrialCancers  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)
  • 36.
    Stage I Intermediate-Risk EndometrialCancers  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)
  • 37.
    Stage I Intermediate-Risk EndometrialCancers  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)
  • 38.
    Stage I Intermediate-Risk EndometrialCancers  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)
  • 39.
    Advanced Stage (IIto 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)
  • 40.
    Five Year SurvivalFiveYear Survival 72%72% diagnosed at this stage I,diagnosed at this stage I, 3%3% Diagnosed at stage IVDiagnosed at stage IV
  • 42.
    Conclusions  Endometrial carcinomais 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.
  • 43.
    Conclusions  The initialmanagement 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.
  • 44.
    Conclusions  Endometrial carcinomahas 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.