#149 Endometrial Cancer Flashcards
What percentage of endometrial cancers are stage I at time of diagnosis?
More than 70%
What is the 5-year survival rate for stage I endometrial cancer?
90%
What is the mean age of diagnosis for endometrial cancer in the US?
63 years
What is the lifetime risk of developing uterine cancer in caucasian and african american women?
2.81% and 2.48%
Compared to caucasian women, African American women are more likely to have what type and stage of endometrial cancer?
More likely to have nonendometrioid, high-grade tumors (type II), more advanced stage of disease (stage III and IV) at the time of diagnosis
What proportion of endometrial cancer cases are type I?
More than 3/4
What histology is associated with type I endometrial cancer?
Endometrioid adenocarcinoma
What histology is associated with type II endometrial cancer?
Clear cell and papillary serous
What is the precursor to type I endometrioid adenocarcinoma?
Endometrial intraepithelial neoplasia
When endometrial intraepithelial neoplasia is absent (in setting of hyperplasia), what is the risk of progression to endometrioid carcionoma?
1-8%, depending on the degree of architectural complexity
What is the 19-year cumulative risk of carcinoma among women with nonatypical endometrial hyperplasia?
4.6%
How frequently is endometrial intraepithelial neoplasia found coexisting with undiagnosed endometrioid carcinoma?
30-50% of cases
When EIN is treated conservatively, what is the 19-year cumulative risk of developing endometrial carcinoma?
27.5%
What percentage of uterine cancers are papillary serous carcinoma?
10%, but make up 40% of deaths
What percentage of deaths from uterine cancer are attributed to papillary serous cancer?
40%, but only make up 10% of cases
What is thought to be the precursor lesion to papillary serous carcinoma?
Endometrial intraepithelial carcinoma
Is clear cell carcinoma of the uterus associated with a good or poor prognosis?
Poor
Does carcinosarcoma of the uterus have a good or poor prognosis?
Poor
What is another name for carcinosarcoma of the uterus?
Malignant mixed mullerian tumor
What are risk factors for Type I uterine cancer?
Older age, residency in N. America or N. Europe, higher level of education or income, white race, nulliparity, hx of infertility, menstrual irregularities, early menarche, late menopause, long-term unopposed estrogen, tamoxifen use, obesity, estrogen-producing tumor, hx T2DM, HTN, gallbladder dx, thyroid dx, Lynch syndrome
What is the minimum number of days per month that progesterone needs to be administered to have a protective effect on endometrium?
10d/month
Does tamoxifen use increase risk of endometrial cancer for all ages?
No. Women 49yo and younger did not have increased risk.
What is the risk ratio for endometrial cancer in women >50yo on tamoxifen?
4.01
Does raloxifene increase risk of endometrial cancer?
No
Does ospemifene increase the risk of endometrial cancer?
Only limited long-term safety data. No cases of endometrial hyperplasia or carcinoma, but dose-related increase in endometrial thickness
What percentage of endometrial cancers are diagnosed before age 50?
15%
What percentage of endometrial cancers are diagnosed before age 40?
5%
Are younger women diagnosed with endometrial cancer more likely to have lower or higher stage disease?
Lower. Typically obese, nulliparous women with well-differentiated endometrioid histology.
How much does a BMI > 35 increase the risk of endometrial cancer in women younger than 45 yo?
22-fold
What is the classic patient with type II endometrial cancer?
Older, non white, multiparous, current smoker
How does smoking affect the risk of endometrial cancer?
Decreased risk of type I endometrial cancer, especially in PMP women, but associated with increased risk of type II endometrial cancer
What genetic conditions/syndromes predispose women to endometrial cancer?
Lynch syndrome and Cowden disease
Association between BRCA gene mutations and risk of endometrial cancer remains controversial, may be d/t Tamoxifen use
What are the mismatch repair genes involved in Lynch syndrome?
MLH1, MSH2, PMS2, MSH6
What is the risk of endometrial cancer with Lynch syndrome?
10-61%
What is the mean age of diagnosis of endometrial cancer in women with Lynch syndrome?
48-50yo
What is the inheritance pattern for Cowden disease?
Autosomal dominant
What is the mutation associated with Cowden disease?
PTEN mutation
What are patients with Cowden disease at risk for?
Breast cancer, thyroid cancer, endometrial cancer
What is the most common symptom(s) of endometrial cancer?
AUB and postmenopausal bleeding
What are symptoms of advanced endometrial cancer?
Abdominal or pelvic pain, abdominal distension, bloating, early satiety, and change in bowel or bladder function
Is there recommendations for routine screening for endometrial cancer in the general population?
No
What is required as part of “comprehensive surgical staging” for endometrial cancer?
Removal of uterus, cervix, adnexa, and pelvic and para-aortic lymph node tissues as well as obtaining pelvic washings
What does pelvic lymphadenectomy refer to (landmarks)?
Removal of the nodal tissue from the distal half of the common iliac artery and vein down to the point at which the deep circumflex iliac vein crosses the external iliac artery, and the obturator fat pad anterior to the obturator nerve
What does para-aortic lymph node dissection refer to (landmarks)?
Removal of nodal tissue over the distal IVC from the level of the IMA to the midright common iliac artery and removal of the nodal tissue between the aorta and left ureter from IMA to midleft common iliac artery.
What is the definition of adequate nodal dissection for endometrial cancer staging?
Lymphatic tissue demonstrated pathologically from right and left, but no minimal nodal counts. – therefore can do selective rather than full dissection
In endometrial cancer, how are survival rates affected by extent of lymph node dissection?
Improved survival rates with multiple site sampling (rather than full dissection) over those who have limited sampling or no sampling.
What percentage of endometrial cancer patients with positive nodes will have those nodes grossly enlarged?
Fewer than 10%
When lymph nodes are involved in metastatic endometrial cancer, what % of the time will para-aortic nodes be involved?
57-67%
How often does isolated para-aortic lymph node involvement occur in the absence of pelvic lymph node mets in endometrial cancer?
16-17% of patients with lymph node involvement
What is the risk of isolated para-aortic lymph node metastases in patients with endometrial cancer?
1 to 3.5%
Does ultrasound measurement of endometrial thickness in premenopausal women have diagnostic value?
No, should not be performed
When should you histologically evaluate the endometrium of a premenopausal woman?
Based on symptomatology and clinical presentation. Not on ultrasound results (they have no diagnostic value)
What is the next step in women with postmenopausal bleeding (after thorough history and physical exam)?
Either EMB or TVUS
At what endometrial thickness in a women with postmenopausal bleeding do you not need to perform endometrial sampling?
4mm or less
What is the next step in a patient with postmenopausal bleeding with ultrasound unable to adequately visualize endometrial thickness?
Endometrial sampling
When would you perform endometrial sampling on a women with postmenopausal bleeding with endometrial stripe less than 3mm?
Persistent or recurrent uterine bleeding
When would you perform D+C hysteroscopy on a women with postmenopausal bleeding with a negative EMB?
Persistent or recurrent uterine bleeding
Is routine preoperative assessments of patients with endometrial cancer with imaging tests recommended?
Not necessarily for routine cases
When would you consider imaging work up for patient with endometrial cancer on EMB?
Poor surgical candidate (d/t medical comorbids), symptoms suggest possible metastasis to unusual sites (eg, bones, CNS), or when pre op histology is high-grade (grade 3 endometrioid, pap serous, clear cell, carcinosarcoma)
Do patient with low-grade, minimally invasive endometrial cancer benefit from comprehensive surgical staging (lymphadenectomy)
No. Difficult to identify these patients, need through extensive frozen sectioning not widely available at many hospitals
What is FIGO stage IA endometrial cancer?
Tumor confined to corpus uteri with no or less than half myometrial invasion
What is FIGO stage IB endometrial cancer?
Tumor confined to corpus uteri with invasion equal to or more than half of the myometrium
What is FIGO stage II endometrial cancer?
tumor invades cervical stroma, but does not extend beyond the uterus
What is FIGO stage IIIA endometrial cancer?
Local and/or regional spread of tumor: tumor invades the serosa of the corpus uteri and/or adnexae
What is FIGO stage IIIB endometrial cancer?
Local and/or regional spread of tumor: Vaginal and/or parametrial involvement
What is FIGO stage IIIC endometrial cancer?
Local and/or regional spread of the tumor: Metastases to pelvic and/or para-aortic lymph nodes
(also IIIC1 and IIIC2)
What is FIGO stage IIIC1 endometrial cancer?
Local and/or regional spread of the tumor: positive pelvic nodes
What is FIGO stage IIIC2 endometrial cancer?
Local and/or regional spread of the tumor: positive para-aortic lymph nodes with or without positive pelvic lymph nodes
What is FIGO stage IV endometrial cancer?
Tumor invades bladder and/or bowel mucosa, and/or distant metastases
What is FIGO stage IVA endometrial cancer?
Tumor invasion of bladder and/or bowel mucosa
What is FIGO stage IVB endometrial cancer?
Distant metastases, including intra-abdominal metastases and/or inguinal lymph nodes
How did GOG-99 define low-intermediate risk group for endometrial cancer?
- Age equal or greater 70yo with no risk factors
- Age 50-69, 0 or 1 risk factor
- Age less than 50, two or less risk factors
Risk factors = grade 2 or 3 histology, positive LVSI, myometrial invasion to outer 1/3
How did GOG-99 define high-intermediate risk group?
- any age with 3 risk factors
- age 50-69 with two or more risk factors
- age 70 or greater with one or more risk factor
Risk factors = grade 2 or 3 histology, positive LVSI, myometrial invasion to outer 1/3
In patients with stage I endometrial cancer identified as belonging to high-intermediate risk group, what is next step?
Radiation therapy, which leads to improved progression-free survival and fewer local recurrences
In patients with stage I endometrial cancer without high-intermediate risk factors, what is next step?
Surveillance, no radiation
What percentage of patients have lymphedema after lymphadenectomy for endometrial cancer staging?
47% according to a 2014 study; further studies pending
How can you avoid lymphedema when doing lymphadenectomy for endometrial cancer staging?
Limit to region cephalad to the deep circumflex iliac vein, avoiding removal of the circumflex iliac nodes distal to the external iliac nodes
What percentage of endometrial cancer staging surgeries are converted from laparoscopy to laparotomy, for what reason?
25.8%, primarily for poor exposure. BMI dependent
Is laparascopy or laparotomy for endometrial cancer staging associated with fewer moderate-to-sever postop adverse events?
Laparoscopy. 14% vs 21%
Is laparascopy or laparotomy for endometrial cancer staging associated with fewer moderate-to-sever intraop adverse events?
Similar rates for both modalities
Is there a survival difference between endometrial cancer staging with laparoscopy vs laparotomy?
No
In which patients would you perform a vaginal hysterectomy for endometrial cancer?
Patients with early-stage endometrioid endometrial cancer with high risk of surgical morbidity
Among patients who have not had radiation therapy for endometrial cancer, what are the outcomes of salvage therapy at the time of recurrence?
Most often curative
How does vaginal brachytherapy compare to whole pelvic radiation in regards to side effect profile?
Vaginal brachytherapy is associated with significantly fewer GI toxic effects as well as better quality of life
In which endometrial cancer patients is vaginal brachytherapy preferred to whole pelvic irradiation?
- > 60yo w/ stage IB, grade 1 or grade 2 disease
- > 60yo w/ Stage IA grade 3 dx w/ myometrial invasion
- Any age with endocervical glandular involvement and disease otherwise confined to uterus (excluding stage IB grade 3)
What % of newly diagnosed cases of endometrial cancer will involve disease spread outside uterus?
10-15%
What percentage of deaths from endometrial cancer are attributable to patients who initially present with disease spread outside the uterus?
50%
What is the survival rate for endometrial cancer with disease spread outside of the uterus at time of diagnosis?
5-15%
What is the treatment approach to patients with endometrial cancer spread outside the uterus?
Multimodal: sugery (w/ cytoreduction), chemotherapy, radiation
What is the definition of optimal surgical cytoreduction?
Less than or equal to 1cm or 2cm
Does optimal cytoreduction surgery improve progression-free and overall survival in endometrial cancer patients?
Yes
What is the median survival for patients with endometrial cancer when tumor is determined to be unresectable?
2-8 months, regardless of further treatment with radiation, chemo, or both
Does secondary cytoreductive surgery for recurrent endometrial cancer improve progression-free and overall survival?
Yes, whether recurrence is localized to pelvis or disseminated throughout the abdomen
On what does survival seem to be dependent in women with recurrent endometrial cancer?
Type of recurrence (solitary vs carcinomatosis), ability to achieve optimal cytoreduction, and time from original treatment to recurrence
What is the median overall survival after secondary cytoreductive surgery for endometrial cancer?
39 to 57 months after surgery
In endometrial cancer patients with localized recurrence who previously had radiation therapy what is the only remaining curative option?
Pelvic exenteration
What is the % of women with post op morbidity and mortality after pelvic exenteration for recurrent endometrial cancer?
Postop morbidity 60-80%
mortality 10-15%
What is the optimal chemotherapy regimen in advanced or recurrent endometrial cancer?
Paclitaxel and carboplatin is as effective as other regimens (paclitaxel, doxorubicin, and cisplatin) with less toxicity
Is there a role for hormone therapy in management of advanced-stage endometrial cancer?
Possibly (tamoxifen + progesterone). Promising activity for hormone therapy for patients who are unable or unwilling to undergo more aggressive therapies, regardless of tumor grade or hormone receptor status
Who are candidates for fertility-sparing treatment of endometrial cancer?
- Well differentiated grade 1 endometrioid endometrial carcinoma
- No myometrial invasion
- No extrauterine involvement
- Strong desire for future fertility
- No contraindications to medical management
- Patient understands and accepts that data on cancer-related and pregnancy-related outcomes are limited
For patients with endometrial cancer desiring fertility-sparing treatment, is it better to diagnose with EMB or D+C?
D+C. More likely to get accurate grade of cancer
At time of hysterectomy what % of endometrial cancers diagnosed by EMB were upgraded? Diagnosed by D+C?
26% of those diagnosed by EMB. 10% of those diagnosed by D+C
In patients with endometrial cancer who desire to preserve fertility, how can you assess for myometrial invasion?
Imaging. MRI may be preferred compared with ultrasound and CT
What is the mainstay of conservative hormonal treatment for endometrial cancer in young women?
Progestins
How often do you need to repeat endometrial sampling in patients undergoing progestin therapy for endometrial cancer?
Every 3 months
Can ovarian preservation be considered for premenopausal women with endometrial cancer?
Yes, with precautions. Survival rate was 93.3%. All recurrence seen in nonendometrioid histology, deep myometrial invasion, cervical stromas invasion, or inadequate adjuvant therapy. No excess deaths associated with ovarian preservation
What is the risk of a synchronous ovarian malignancy in premenopausal women with endometrial cancer?
Up to 19%, which is why BSO should be strongly considered
If endometrial cancer is incidentally found on hysterectomy specimen, which patients should go for second surgery for comprehensive cancer staging?
Those with higher risk of extrauterine spread or recurrence: high-risk histologic cell types, grade 3 tumors, deep myometrial invasion.
What is recommended surveillance after endometrial cancer treatment?
Follow up every 3-6 months for two years, then every 6 months for 3 years, then annually after that
What should be covered at a surveillance visit for endometrial cancer patient?
History, elicitation and investigation of any new symptoms associated with recurrence such as vaginal bleeding, pelvic pain, weight loss, lethargy. Thorough speculum, pelvic, and rectovaginal exam.
What is the role of imaging of endometrial cancer patients after treatment during surveillance?
Imaging (CT or PET/CT) only used to investigate suspicion of recurrent disease, not for routine surveillance after treatment
Can estrogen therapy be used for symptomatic women who are survivors of early-stage endometrial cancer?
Can be considered after thorough counseling about the risks and benefits
What is the method of choice for outpatient histologic evaluation of the endometrium?
EMB with disposable devices - reliable and accurate