Endometrial Cancer Tseng Jen-Yu 02/05/2007 Tseng Jen-Yu 02/05/2007.

Endometrial CancerEndometrial Cancer

Tseng Jen-Yu

02/05/2007Tseng Jen-Yu

02/05/2007

OverviewOverview Origin => Uterine endometrial lining Most common gynecologic malignancy 35,000 cases diagnosed each year Resulting in 4000 ~ 5000 deaths Normally occurs in postmenopausal Average age at diagnosis => 60 y/o < 5% under age of 40 Lifetime risk: 1.1% Lifetime risk of dying: 0.4%

Origin => Uterine endometrial lining Most common gynecologic malignancy 35,000 cases diagnosed each year Resulting in 4000 ~ 5000 deaths Normally occurs in postmenopausal Average age at diagnosis => 60 y/o < 5% under age of 40 Lifetime risk: 1.1% Lifetime risk of dying: 0.4%

Estrogen dependent disease Prolonged exposure without the balancing effects o

f progesterone Premalignant potential

Endometrial hyperplasia Simple => 1% Complex => 3% Simple with atypia => 8% Complex with atypia => 29%

Estrogen dependent disease Prolonged exposure without the balancing effects o

f progesterone Premalignant potential

Endometrial hyperplasia Simple => 1% Complex => 3% Simple with atypia => 8% Complex with atypia => 29%

Incidence and PrevalenceIncidence and Prevalence Most common gynecologic cancer 4th most common in women (US) 2nd most common in women (UK) 5th most common in women (worldwide) Western developed > Southeast asia 35,000 new cases annually 5,000 death annually Increase in the 1970’s

Increased use of menopausal estrogen therapy

Most common gynecologic cancer 4th most common in women (US) 2nd most common in women (UK) 5th most common in women (worldwide) Western developed > Southeast asia 35,000 new cases annually 5,000 death annually Increase in the 1970’s

Increased use of menopausal estrogen therapy

TypesTypes 90% endometrial adenocarcinoma Arise from the epithelium Tumor grading

Grade 1 Well differentiated

Grade 2 Moderately differentiated with solid component

Grade 3 Poorly differentiated with solid sheets of tumor

90% endometrial adenocarcinoma Arise from the epithelium Tumor grading

Grade 1 Well differentiated

Grade 2 Moderately differentiated with solid component

Grade 3 Poorly differentiated with solid sheets of tumor

10% rare cell types Papillary serous carcinoma Clear cell carcinoma Papillary endometrial carcinoma Mucinous carcinoma

Rarer cancers Onset at later age Greater risk for metastases Poorer prognosis 50% of treatment failure

10% rare cell types Papillary serous carcinoma Clear cell carcinoma Papillary endometrial carcinoma Mucinous carcinoma

Rarer cancers Onset at later age Greater risk for metastases Poorer prognosis 50% of treatment failure

Risk FactorsRisk Factors Obesity

Excess weight have 2 ~ 5 x greater risk Fat cells (adipocytes) produce estrogen

Diabetes Mellitus and Hypertension DM women have 2 x greater risk

Nulliparity Progesterone counterbalances estrogen Pregnancy lowers risk

Obesity Excess weight have 2 ~ 5 x greater risk Fat cells (adipocytes) produce estrogen

Diabetes Mellitus and Hypertension DM women have 2 x greater risk

Nulliparity Progesterone counterbalances estrogen Pregnancy lowers risk

Early Menarche and Late Menopause Associated with more estrogen exposure

Estrogen Replacement Therapy Place women at high risk Risk reduced when + progesterone

Tamoxifen Anti-estrogenic drug for breast cancer Side effect

Induces non-cancerous uterine tumors Some may develop into endometrial cancer Long term use => endometrial cancer Only 1 in 500 develop endometrial cancer

Early Menarche and Late Menopause Associated with more estrogen exposure

Estrogen Replacement Therapy Place women at high risk Risk reduced when + progesterone

Tamoxifen Anti-estrogenic drug for breast cancer Side effect

Induces non-cancerous uterine tumors Some may develop into endometrial cancer Long term use => endometrial cancer Only 1 in 500 develop endometrial cancer

Genetic Predisposition Risk may approach 50% in some families

Previous Cancer History of breast / colon / ovarian cancer are at

increased risk Time interval can be as long as 10 years

Diet Association is still unclear Diet rich in animal fat and protein => risk ^ Diet rich in vegetable, fruits, grain=> risk v

Genetic Predisposition Risk may approach 50% in some families

Previous Cancer History of breast / colon / ovarian cancer are at

increased risk Time interval can be as long as 10 years

Diet Association is still unclear Diet rich in animal fat and protein => risk ^ Diet rich in vegetable, fruits, grain=> risk v

Reduced RiskReduced Risk Oral Contraceptives

Combined OC => 50% reduced rate Actual reduction number small because

uncommon in women of child bearing age Long term offers protection Reduced risk presumably => progesterone

Tobacco Smoking Some evidence that it reduces the rate Smokers have lower levels of estrogen and lower

rate of obesity

Oral Contraceptives Combined OC => 50% reduced rate Actual reduction number small because

uncommon in women of child bearing age Long term offers protection Reduced risk presumably => progesterone

Tobacco Smoking Some evidence that it reduces the rate Smokers have lower levels of estrogen and lower

rate of obesity

Prevention and SurvivalPrevention and Survival Early detection is best prevention Treating precancerous hyperplasia

Hormones (progestin) D&C Hysterectomy 10 ~ 30% untreated develop into cancer

Average 5 year survival Stage I => 72 ~ 90% Stage II=> 56 ~ 60% Stage III => 32 ~ 40% Stage IV => 5 ~ 11%

Early detection is best prevention Treating precancerous hyperplasia

Hormones (progestin) D&C Hysterectomy 10 ~ 30% untreated develop into cancer

Average 5 year survival Stage I => 72 ~ 90% Stage II=> 56 ~ 60% Stage III => 32 ~ 40% Stage IV => 5 ~ 11%

SignsSigns Postmenopausal vaginal bleeding Abnormal uterine bleeding

Bleeding in between periods Heavier / longer lasting menstrual bleeding

Abnormal vaginal discharge / Pyometra Pelvic or back pain Pain on urination Pain on sexual intercourse Blood in stool or urine

Postmenopausal vaginal bleeding Abnormal uterine bleeding

Bleeding in between periods Heavier / longer lasting menstrual bleeding

Abnormal vaginal discharge / Pyometra Pelvic or back pain Pain on urination Pain on sexual intercourse Blood in stool or urine

DiagnosisDiagnosis Endometrial sampling

Dilation and curettage / Endometrial aspiration Image

TVS / CT scan / MRI Standard

Hysteroscopy + targeted biopsy Tumor marker

Ca 125 / 199 Cystoscope / Proctoscope

Endometrial sampling Dilation and curettage / Endometrial aspiration

Image TVS / CT scan / MRI

Standard Hysteroscopy + targeted biopsy

Tumor marker Ca 125 / 199

Cystoscope / Proctoscope

Staging Staging Stage I

Tumor confined to uterine body Stage Ia

Tumor limited to endometrium Stage Ib

Tumor invades less than ½ of myometrium Stage Ic

Tumor invades more than ½ of myometrium

Stage II Tumor extends to the cervix Stage IIa

Cervical extension limited to endocervical glands Stage IIb

Tumor invades cervical stroma

Stage I Tumor confined to uterine body Stage Ia

Tumor limited to endometrium Stage Ib

Tumor invades less than ½ of myometrium Stage Ic

Tumor invades more than ½ of myometrium

Stage II Tumor extends to the cervix Stage IIa

Cervical extension limited to endocervical glands Stage IIb

Tumor invades cervical stroma

Stage III Regional tumor spread Stage IIIa

Tumor invades serosa / adnexa / peritoneum / ascites (+)

Stage IIIb Vaginal involvement / metastases present

Stage IIIc Tumor spread to pelvic LN

Stage IV Bulky pelvic disease or distant spread Stage IVa

Tumor has spread to bladder or rectum

Stage IVb Distant metastases present / inguinal LN

Stage III Regional tumor spread Stage IIIa

Tumor invades serosa / adnexa / peritoneum / ascites (+)

Stage IIIb Vaginal involvement / metastases present

Stage IIIc Tumor spread to pelvic LN

Stage IV Bulky pelvic disease or distant spread Stage IVa

Tumor has spread to bladder or rectum

Stage IVb Distant metastases present / inguinal LN

SpreadSpread Direct spread

Through endometrial cavity to the cervix Through fallopian tubes to ovary / peritoneum Invade myometrium reaching serosa Rare: invasion to pubic bone

Lymphatic spread Pelvic and para-aortic LN Inguinal LN ( rare )

Hematogenous spread Rare but may spread to lungs

Direct spread Through endometrial cavity to the cervix Through fallopian tubes to ovary / peritoneum Invade myometrium reaching serosa Rare: invasion to pubic bone

Lymphatic spread Pelvic and para-aortic LN Inguinal LN ( rare )

Hematogenous spread Rare but may spread to lungs

TreatmentTreatment Surgery

Early stage ( I and II ) Typical surgery is ATH + BSO + BPLND VTH + BSO + laparoscopic BPLND LAVH + BPLND

Advanced stage Debulking surgery Radiotherapy +/- hormone / chemotherapy

Surgery Early stage ( I and II )

Typical surgery is ATH + BSO + BPLND VTH + BSO + laparoscopic BPLND LAVH + BPLND

Advanced stage Debulking surgery Radiotherapy +/- hormone / chemotherapy

Radiation External beam pelvic radiation

Reserve use of radiotherapy until post-ATH Adjuvant radiation therapy is controversial Regional pelvic radiation proven to decrease pelvic r

ecurrence Not necessarily improve survival rate Most beneficial for patients with tumor confined to th

e pelvis Patients with increased likelihood of recurrence

( Stage Ic to IIIc) Brachytherapy

Prevent vaginal cuff recurrence

Radiation External beam pelvic radiation

Reserve use of radiotherapy until post-ATH Adjuvant radiation therapy is controversial Regional pelvic radiation proven to decrease pelvic r

ecurrence Not necessarily improve survival rate Most beneficial for patients with tumor confined to th

e pelvis Patients with increased likelihood of recurrence

( Stage Ic to IIIc) Brachytherapy

Prevent vaginal cuff recurrence

Hormonal therapy Progesterone => for metastatic cancer Less than 20% response rate

Chemotherapy No clear results on effectiveness Potentially most useful in metastatic cancer Not as important as surgery and radiation Only used in advanced or recurrent tumor after

definitive treatment with surgery and radiation

Hormonal therapy Progesterone => for metastatic cancer Less than 20% response rate

Chemotherapy No clear results on effectiveness Potentially most useful in metastatic cancer Not as important as surgery and radiation Only used in advanced or recurrent tumor after

definitive treatment with surgery and radiation

RecurrenceRecurrence Likely in women with advanced disease Within 3 years of original diagnosis Hormone therapy can be considered Use of chemotherapy is being evaluated External beam pelvic radiation or brachyth

erapy

Likely in women with advanced disease Within 3 years of original diagnosis Hormone therapy can be considered Use of chemotherapy is being evaluated External beam pelvic radiation or brachyth

erapy

Thank you for your attentionThank you for your attention