Endometrial Cancer

corpus uteri carcinoma

Outline

definition epidemiology

Subtypes
Approach to the patient prognosis followup case study /questions

Definition
Refers to several types of malignancies
that arise from the endometrium.

Epidemiology
Corpus uteri is the 6th most common
cancer for women in the world

It is the leading gynocological cancer in

the developed world

2nd most common gynocological

cancer in developing world

It ranks 7th in less developed regions

World
Incidence 4.8% ASR (W)8.2 mortality 2.2%

Text

Developed Regions
All regions of Europe plus Northern America, Australia/New Zealand and Japan.

Incidence 5.5% ASR (W)13 mortality 2.7%

Caribbean
Incidence 5.7% ASR (W)9 mortality 3.8%

Barbados
Incidence 7.3% ASR (W)13 mortality 5.5%

Jamaica
Incidence 7% ASR (W)14.9 mortality 4.9%

Trinidad
Incidence 9% ASR (W)10.8 mortality 15.5%

Histological Types
Endometrioid (75%80%)

Ciliated adenocarcinoma. Secretory adenocarcinoma. Papillary or villoglandular. Adenocarcinoma with squamous differentiation.

Adenoacanthoma.
Adenosquamous

 Uterine papillary serous (<10%). Clear cell (4%). Mucinous (1%). Squamous cell (<1%). Mixed (10%). Undifferentiated.

Histological Grades

Well differentiated, G1 5% of non-squamous or non-morula solid growth or pattern

Moderately differentiated, G2
650% of a non-squamous or non-morula solid growth pattern

Poorly differentiated, G3
>50% of a non-squamous or non-morula solid growth pattern

Pathophysiology
Two biologically different subtypes,
implying two different mechanisms for its origin.

Low Risk Subtype High-Risk Subtype

Low-Risk Subtype
The most common subtype Well-differentiated carcinoma (grade 1
or 2 endometrioid histology)

Causes bleeding symptoms in its early

stages,

Curable in most cases

Risk factors
postmenopausal status 3x

body mass index (BMI) >25 kg/m2 or more >30 pounds over ideal weight >50 pounds over ideal weight
unopposed exogenous estrogen nulliparous late menopause diabetes mellitus hypertension complex atypical hyperplasia tamoxifen

10 x

9.5 x 2x 2.4 2.8 x 1.5 x 29 x 3x

Risk reduction factors

Normal weight Physically active Pregnancy Oral contraceptives Smoking decreases the risk of

Progestins even when administered in

combination with estrogen replacement.

endometrial cancer

High-Risk Subtype


Minority of endometrial malignancies Poorly differentiated tumors (grade 3 endometrioid, clear cell, and papillary serous carcinoma)

Not associated with increased circulating estrogens

More common in blacks.

Spontaneously occur in postmenopausal

No clearly defined risk factors

 These tumors metastasize early Account for a disproportionate number

of mortalities from endometrial malignancy

Modes of spread include local invasion

and lymphatic and vascular embolization.

The most common metastatic sites

include the cervix, adnexa, and retroperitoneal lymph nodes.

Approach the Patient

Approach to Patient
Clinical history Physical examination Investigations Ancillary tests Surgical staging

History and Presntation

Presentation
Approximately 75% of women with
endometrial cancer are postmenopausal,

Most common symptom is

postmenopausal bleeding.

Approximately 20% of postmenopausal

bleeding is due to cancer

Presentation
25% of endometrial cancers are in
patients who are perimenopausal or premenopausal, symptoms suggestive of cancer may be more subtle.

History
Demographics Age of over 50 years, Presenting Complaint Abnormal vaginal bleeding,
which may range from simple menorrhagia to a completely disorganised bleeding pattern.

History of Presenting Complaint

Abdominal Distention Persistent pain (especially in the abdomen or pelvic region), Fatigue, Weight loss

Past medical History Hereditary non-polyposis colon cancer (Lynch syndrome), Bowel Cancer Breast Cancer Diabetes Polycystic Ovarian Syndrome

Review Of Systems

diarrhea,nausea or vomiting,

weight loss,
persistent cough, swelling Difficult or painful urination. Pain during sexual intercourse. new-onset neurological symptoms.

Low Risk Subtype

Postmenopausal bleeding in majority,
abnormal uterine bleeding in majority of affected pre-menopausal women (menorrhagia, intermenstrual bleeding)

High Risk Subtype

May not present with bleeding in early
stage

More likely to present with advanced

stage disease with symptoms like ovarian cancer

bloating, bowel dysfunction pelvic pressure

Examination
General examination Abdominal examination Pelvic examination

Diagnostic procedures
Endometrial Biopsy Confirms diagnosis histologically Identifies tumor subtype and grade Allows biomarker analysis using performed with a disposable plastic
tool (Pipelle de Cournier) immunohistochemistry

Diagnostic Procedure

Dilatation and Curettage and endometrial biopsy

Hysteroscopy and endometrial biopsy

Investigations

PAP smear Primarily used to screen for cervical dysplasia Not a screening test for endometrial cancer 50% of cases it can identify abnormalities higher up in the genital tract. Atypical glandular cells on cervical cytology should prompt immediate evaluation with an endometrial sampling

Laboratory Investigation
Diagnostic Assessment for surgery

 FBC Anemia Kidney function: urea and creatinine Elevated creatinine may suggest
renal system involvement or obstruction.

 Liver Function Test Elevated alkaline phosphatase if Ca 125 Non specific for endometrial
carcinoma metastatic spread to bones or liver

Aid in monitoring Typically <35 units/mL (depending on

laboratory)

Imaging
Vaginal (transvaginal) ultrasound An endometrial thickness < 5mm, HRT < 7mm, tamoxifen <
8mm

Hydroultrasound

Imaging
A CT scan of the pelvis An MRI of the pelvis A chest X-ray A bone scan

Staging

Definitive staging is done surgically

Anatomy

Anatomy

Blood Supply
Blood supply uterine arteries Branch of internal iliac artery The ovarian artery Branch of the aorta

Blood Supply

Lymphatics
Most of the lymphatic vessels from the
pelvis drain into groups of nodes associated with the iliac arteries and their branches

External iliac
External iliac lymph nodes receive
vessels

Inguinal nodes External genitalia Upper vagina, Cervix Uterine corpus (upper)

Internal Iliac

Internal iliac and sacral lymph nodes receive afferents from all the pelvic viscera

Cervix

Rectum
Perineum Buttock

Thigh
Upper vagina Uterine corpus (lower)

Common Iliac
Common iliac lymph nodes drain the
two preceding groups and send their efferents to the lumbar group of aortic nodes

Para Aortic
Ovary Fallopian tube Uterine corpus (upper) Drainage from common iliac nodes

Staging
TNM FIGO stages Surgical-pathologic findings

TX
T0 Tis* T1 T1a I IA

Primary tumor cannot be assessed

No evidence of primary tumor Carcinoma in situ (preinvasive carcinoma) Tumor confined to corpus uteri Tumor limited to endometrium or invades less than one half of the myometrium

T1b

IB

Tumor invades one half or more of the myometrium

TNM

FIGO stages

Surgical-pathologic findings

T2

II

Tumor invades stromal connective tissue of the cervix but does not extend beyond uterus**

TNM

FIGO stages

Surgical-pathologic findings

T3a

IIIA

Tumor involves serosa and/or adnexa (direct extension or metastasis) Vaginal involvement (direct extension or metastasis) or parametrial involvement Metastases to pelvic and/or para-aortic lymph nodes Tumor invades bladder mucosa and/or bowel mucosa, and/or distant metastases Tumor invades bladder mucosa and/or bowel mucosa (bullous edema is not sufficient to classify a tumor as T4)

T3b

IIIB

IIIC

IV

T4

IVA

Regional lymph nodes (N) FIGO TNM stages NX N0 N1 IIIC1 Surgical-pathologic findings

Regional lymph nodes cannot be assessed

No regional lymph node metastasis Regional lymph node metastasis to pelvic lymph nodes Regional lymph node metastasis to para-aortic lymph nodes, with or without positive pelvic lymph nodes

N2

IIIC2

Distant metastasis (M)

FIGO TNM stages M0

Surgical-pathologic findings No distant metastasis Distant metastasis (includes metastasis to inguinal lymph nodes, intraperitoneal disease, or lung, liver, or bone metastases; it excludes metastasis to para-aortic lymph nodes, vagina, pelvic serosa, or adnexa)

M1

IVB

Treatment

Treatment Options
Surgical Adjuvant Therapy Radiation therapy Chemotherapy Hormone therapy

Surgery

Other Procedures
Peritoneal lavage Omentectomy Peritoneal biopsies Tumor debulking

Radiation Therapy
Vaginal Brachytherapy Pelvic Radiation External beam radiotherapy

 Paclitaxel Mechanism of Action: Natural taxane, Doxorubicin Mechanism of Action:Anthracycline;

prevents depolymerization of cellular microtubules, which results in DNA, RNA, and protein synthesis inhibition

Chemotherapy

intercalates between DNA base pairs, impairs topo II function and inhibits replication & transcription

Chemotherapy

Cisplatin

Mechanism of Action: Platinum coordination compound that inhibits DNA synthesis; cross-links and denatures strands of DNA; disrupts DNA function by covalently binding to DNA bases; can also produce DNA intrastrand cross-linking and breakage

Carboplatin

Mechanism of Action:Platinum coordination compound; covalently binds to DNA; cross-links strands of DNA

Hormone therapy or Aromatase inhibitor

Tamoxifen

Mechanism of Action: Selective estrogen receptor modulator: nonsteroid with potent antiestrogenic effects in breast has cytostatic effect rather than cytocidal effects (cells accumulate in Go and G1 phase of the cell cycle) Megestrol

Mechanism of Action: Progestin derivative with antiestrogenic properties; interferes with estrogen cycle, resulting in lower luteinizing hormone (LH) titer; antineoplastic properties may come from direct effect on endometrium through anti-LH effect mediated via pituitary

 medroxyprogesterone Mechanism of Action: Progestin;

inhibits secretion of gonadotropins from pituitary gland, prevents follicular maturation and ovulation, and stimulates growth of mammary tissues

letrozole Mechanism of Action: Aromatase

inhibitor - blocks conversion of adrostenedione to estroney

Stage 1

A total hysterectomy and bilateral salpingo-oophorectomy should be done if the tumor: Is well or moderately differentiated. Involves the upper 66% of the corpus. Has negative peritoneal cytology. Is without vascular space invasion. Has less than a 50% myometrial invasion. Selected pelvic lymph nodes may be removed. If they are negative, no postoperative treatment is indicated. Postoperative treatment with a vaginal cylinder is advocated by some clinicians

Stage 11

Standard treatment options: If cervical involvement is documented, options include radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic and para-aortic lymph node dissection. If the cervix is clinically uninvolved but extension to the cervix is documented on postoperative pathology, radiation therapy should be considered.

Stage 111
patients with stage III endometrial
cancer are treated with surgery, followed by chemotherapy, or radiation therapy, or both.

Metastatic Disease

IV endometrial cancer are treated with surgery, followed by chemotherapy, or radiation therapy, or both
IV endometrial cancer is dictated by the site of metastatic disease and symptoms related to disease sites. For bulky pelvic disease,

radiation therapy

intracavitary and external-beam radiation therapy

When distant metastases

hormonal therapy

Recurrent Disease
For patients with localized
radiation therapy or recurrent distant metastases in selected sites

Patients positive for estrogen and

progesterone

Respond best to progestin therapy.

Complications
Excessive bleeding Wound infection Damage to the urinary Damage to intestinal systems.

Side Effects
Infertility Menopause

Complications bladder instability following surgery vaginal stenosis, atrophy, and fibrosis following radiotherapy long-term sexual dysfunction following treatment local or distant spread

Timeframe

Likelihood

long term

high

long term

high

long term

medium

variable

medium

lymphoedema toxicity associated with chemotherapy bowel or bladder fistulae following radiotherapy

variable

medium

variable

medium

variable

low

Prognosis

Prognosis
Generally prognosis is good Diagnosis: 70% to 75% of cases are in stage I 10% to 15% in stage II 10% to 15% in stage III or IV

Prognosis
The 5-year survival rate for all types
and grades of endometrial adenocarcinoma, following treatment:

75% to 95% for stage I 50% for stage II 30% for stage III Less than 5% for stage IV

Prognosis
For stage I endometrioid endometrial
adenocarcinoma,

5-year survival rates per grade Grade 1 - 92% Grade 2 - 87% Grade 3 - 74%

Follow Up

Follow Up
Women who had low grade
endometrioid cancers (grades 1 and 2) that were stage IA

may be seen every 6 months for the

first year after treatment,

yearly after that.

Follow Up
If the cancer was stage IB or II follow-up visits are more frequent every 3 months for the first year then every 6 months for the next 4
years

then once a year.

Follow

For women with higher stage or grade cancers (stages III or IV, or cancers that were grade III, including papillary serous, clear cell, or carcinosarcomas) Experts recommend visits
every 3 months for the first 2 years every 6 months for the next 3 years

yearly after that

Most endometrial cancer recurrences are found within the first few years of follow-up.

Follow Up Visits
Pelvic exam (using a speculum) Check for any enlarged lymph nodes in
the groin area.

A Pap test may also be done to look for

cancer cells in the upper part of the vagina,

Sometimes a CA 125 blood test is done

as a part of follow-up

Follow up Visits

Ask about any symptoms that might point to cancer recurrence or side effects of treatment. If symptoms or the physical exam results suggest the recurrence Imaging tests

CT scans

ultrasound studies
CA 125 blood test biopsies may be done.

Recomendations
Maintain a healthy weight by eating a
moderate, nutrition-rich diet and exercising regularly.

Consider taking birth control pills if

warranted situation and medical condition.

Avoid treatment with unopposed

estrogens

Case History

Case History
72year old Grace Turner has been
recently diagnose with endometrial carcinoma and is being admitted to hospital.

Significant findings in History

BMI 35.3 (156 cm/ 86 kg) Hypertension from 10 years Diabetes from 1 year Smoker for 40 years Cholecystectomy 1998 Partial thyroidectomy 2000 Family history Father: lung cancer Mother & sister :melanoma

abnormal uterine bleeding in April 2009 (after 24 years)

Case

TAH, BSO, abdominal washing No palpable nodes in pelvic and paraaortic area Final histology: Adenocarcinoma endometrioides endometrii G1 CIN1 Invasion in uterus less than 12 of myometrium Cancer in uterus less than 2 cm in diameter

abnormal uterine bleeding in April 2009 (after 24 years) D & C Adenocarcinoma G1

PE normal uterus
transvaginal us: small fibroids and endometrium 6mm

normal X-ray
abdominal US no changes abdominal CT not done

THANK YOU

References

Routes of lymphatic spread: a study of 112 consecutive patients with endometrial cancer.Mariani A, Webb MJ, Keeney GL, Podratz KCSourceDepartment of Obstetrics and Gynecology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study. ASTEC study group, Kitchener H, Swart AM, Qian Q, Amos C, Parmar MK. National Cancer Institute: PDQ Endometrial Cancer Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://cancer.gov/cancertopics/pdq/treatment/endometrial/HealthProfessiona l. Accessed <MM/DD/YYYY>. gynecologic tumors: N. Colombo, E. Preti, F. Landoni, S. Carinelli, A. Colombo, C. Marini, C. Sessa, and On behalf of the ESMO Guidelines Working Group Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up Ann Oncol (2011) 22 (suppl 6): vi35-vi39 doi:10.1093/annonc/mdr374