Uterine Cancer

Amita Maheshwari

Assoc. Professor of Gynecologic

Oncology
Tata Memorial Hospital
maheshwariamita@yahoo.com

Introduction
The most common gynecologic cancer in
developed countries.
In India, it ranks third amongst gynecologic
cancer.
70% cases are diagnosed in stage-I.
5-year survival rate ~80%.

Factors increasing risk

Risk factors

Increased exposure to unopposed estrogen

estrogen-replacement therapy, obesity, anovulatory cycles,
estrogen-secreting tumors

Nulliparity
Years of menstruation
HNPCC family syndrome
Tamoxifen
Increasing age

Factors decreasing risk

Grand multiparity
Oral contraceptives
Smoking
Physical activity

Role of Screening
Routine screening NOT recommended.
1. Postmenopausal women on exogenous estrogens
without progestins
2. Women from families with hereditary
nonpolyposis colorectal cancer syndrome.
3. Premenopausal women with anovulatory cycles,
such as those with polycystic ovarian disease

Patients in Whom a Diagnosis of Endometrial

Cancer Should Be Excluded
1. All patients with postmenopausal bleeding
2. Postmenopausal women with a pyometra
3. Asymptomatic postmenopausal women with endometrial
cells on a Pap smear, particularly if they are atypical
4. Perimenopausal patients with inter-menstrual bleeding
or increasingly heavy periods
5. Premenopausal patients with abnormal uterine bleeding,
particularly if there is a history of anovulation

Causes of Postmenopausal Bleeding

Atrophic endometritis/vaginitis
Endometrial or cervical polyps
Exogenous estrogens
Endometrial hyperplasia
Endometrial cancer
Miscellaneous (e.g., cervical cancer, uterine
sarcoma, urethral caruncle, trauma)

Management of endometrial hyperplasia

Diagnosis & Pre-op investigations

Office endometrial biopsy: 10% false negative rate.
Fractional curettage under anesthesia: The gold
standard.
Hysteroscopy : may identify polyps
Fluid hysteroscopy may facilitate the abdominal dissemination of
malignant cells, but there is no evidence that it has any impact on
the disease-free survival.

X-ray chest, USG, CT scan, MRI, PET-CT,

Serum CA-125
CBC, Renal function tests, Liver function tests, Blood sugar

WHO histological classification

Clinico-pathologic Types

Type-1 (low grade): ~90%

Eo related- Arise on a background of hyperplasia.
Long duration of unopposed estrogenic stimulation.
Well-moderately differentiated.
Favorable prognosis.

Type-2 (high grade): ~10%

Eo non-related- Arise in atrophic endometrium.
Non-estrogen dependent.
Poorly differentiated or non-endometroid types.
High risk of relapse and metastasis.
Prognosis poor.

Ca-Endometrium & Ca-Ovary

~8% Ca-endometrium associated with simultaneous
presence of endometroid type Ca-ovary.
Synchronous: Independent primary
Both tumors are well differentiated and endometrial
tumor is superficially invasive.

Metastatic: small, bilateral, or multi-nodular with surface

implants and angiolymphatic invasion in the ovarian cortex.

D/Dx: by IHC and molecular genetic.

Spread Patterns
Direct extension to adjacent structures
Transtubal passage of exfoliated cells
Lymphatic dissemination
Hematogenous dissemination

Management of Endometrial Ca
1900s

Primary surgery

Mid 1930s

Pre-operative RT

1970s

Primary surgery- clinical staging

1988

FIGO Surgico-pathological staging

2008

Revised FIGO staging

FIGO Surgico-pathologic staging

(1988 vs 2008)

St.-I
Tumor confined to the corpus uteri
IA
IA No myometrial
No or invasion
< half myometrial invasion
IB
invasion < invasion
half
IB Myometrial
Myometrial
half
IC Myometrial invasion half

St.-II
II
IIA
IIB

Cervical involvement
Tumor glandular
invades involvement
cervical stroma
Cervical
Cervical stromal involvement

Revised FIGO staging. IJGO, 2009

FIGO Surgico-pathologic staging

St.-III

(1988 vs 2008)

Local and/or regional spread

IIIA
Tumor invades the serosa of the uterus
and/or positive cytology
IIIB
Vaginal involvement
parametrial involvement
IIIC Pelvic and or para-aotic LN involvement

IIIC1
St.-IV
IIIC2
IVA
IVB

and/or adnexa

Positive
pelvic bladder
nodes and/or bowel
Tumor
invades
mucosa
distant metastases
Positiveorpara-aortic
nodes pelvic LNs
Invasion of bladder and/or bowel mucosa
Distant metastases

FIGO-Grade
Applies to Endometroid type; serous and clear
cell carcinomas are considered to be high
grade.
Grade 1: well formed glands with 5% solid,
non-squamous areas.
Grade 2: 6%-50% solid non-squamous areas.
Grade 3: >50% solid non-squamous areas.

Steps of Surgical Staging

Peritoneal washings for cytology
Exploration of the abdomen & pelvis
Biopsy of any suspicious lesion
Total hysterectomy + BSO*
Pelvic & para-aortic lymphadenectomy
* Ovarian preservation

Value of Surgical Staging

Prognostic:

Accurately defines the extent of disease spread

Upstaging in up-to 23% clinical stage I

Determines the prognosis

Adjuvant Rx:
Determines the need for and extent of adjuvant
treatment
Therapeutic:

Prognostic Value of Lymph Node Metastases

Nodal Status

5-year survival

Negative LN

90%

Positive pelvic LN

75%

Positive para-aortic LN

38%

-Morrow et al. Gynecol Oncol,1991

Morbidity of Lymphadenectomy
Intra-operative:
Blood loss
Visceral injuries
Neuro-vascular injuries

Post-operative:
Thrombo-embolism
Lymphocele
Lower limb/abdominal wall edema
GI complications

Controversies in the surgical staging

Complete surgical staging including pelvic and para-aortic
lymphadenectomy for all patients.
Complete surgical staging NOT needed for any patient.
Uterine risk factors are sufficient to identify high risk
cases.
An identifiable group of intermediate/high risk patients
will benefit from complete staging while those at low risk
will not.

Predictors of LN Metastases
Depth of myometrial invasion
Tumor grade
Tumor size >2cm
Extra-uterine disease
Lymph vascular space invasion
Histologic sub-types type II

Risk Stratification

Low risk: grade 1 or 2 histology with inner half of

myometrial invasion,<2cm size, endometroid sub-type, without
evidence of intra-peritoneal disease

LN mets.

3-5%

High risk: grade 3 histology, any grade with deep myometrial

invasion, non-endometroid sub-type or extra-uterine disease

LN mets

10% - 20%

Extent of Lymphadenectomy

Para-aortic
LN
Common iliac LN
External iliac LN

Extent of Lymphadenectomy
Fifty percent of patients with pelvic node
metastases will have additional para-aortic
nodal metastases.
In 25% patients, para-aortic lymph node
metastases can occur with negative pelvic nodes
Para-aortic LN involvement can occur above the
IMA to the renal vessels directly

Role of Adjuvant Therapy

Adjuvant therapy decisions -- Based on prognostic factors

Prognostic factors

Age
Histologic type
Histologic grade
Myometrial invasion
Vascular space invasion
Tumor size
Hormone receptor status
DNA ploidy and other biological markers

Risk stratification & Adjuvant Rx

Risk Category

Extent of disease

Adjuvant treatment

Low Risk

Superficial invasion (<1/2)

Low grade (1/2)

No further Rx

Intermediate Risk

High Grade
Deep Invasion
LVSI
Negative Lymph Nodes

Vaginal Brachytherapy

High Risk

Positive Lymph Nodes

Stage II
UPSC, CCCa
Positive P-A LNs

External pelvic irradiation and

vaginal brachytherapy -/+CT
CT + Extended field RT

Mx of Advanced/recurrent disease
Multimodality Rx Sx, RT, CT, HT.
Surgical cytoreduction in appropriately
selected cases: Pts. with optimal
cytoreduction have better survival than those
with sub-optimal cytoreduction

Follow up protocol
Every 3 mthly for 2 years

Every 6 mthly for 3 years

Annually life long

History
Clinical examination
Vaginal cytology
Radiological tests

Role of Minimally Invasive Surgery

Laparoscopy seems to be an appropriate

alternative to open surgery

Laparoscopic pelvic lymphadenectomy

Robotic Surgery
Robotic surgery for Endometrial-Ca can be
accomplished in heavier patients and results in
shorter operating times and hospital stay, a lower
transfusion rate, and less frequent conversion to
laparotomy compared to laparoscopy.
- Seamon et al. Gynecol Oncol,2009

Robotic Surgery For Endometrial Cancer

Vaginal Surgery for Endometrial Ca

Vaginal hysterectomy with BSO:
Extreme obesity
Significant medical co-morbidity
Well differentiated tumors
Disadvantages
Upper abdominal exploration is not possible
Lymph nodes cannot be addressed

Endometrial Ca in Young Women

Fertility preservation
Early stage, grade 1 and PR positive.
MRI to exclude significant myometrial invasion and
adequate imaging of the ovaries
High dose progestins: megestrol acetate orally
160 to 320 mg/day or medroxyprogesterone acetate
200 to 500 mg/day
40% of these patients will carry a successful pregnancy.
Hysterectomy is recommended once childbearing has
been completed

Mx of Incompletely Staged Patient

Review HPR- Grade, Invasion, adnexa

CT/MRI/ PET-scan
No gross disease
IA,IB
G1,2
Observe

Gross disease

IC, any grade

IIA,IIB
Restaging

Pelvic RT

Surgical removal
RT +/-CT

Conclusions
Disease of postmenopausal women.
Symptoms occur early in the course: most women
have early stage disease at presentation.
Overall 5-year survival ~80%.
Type-1 (low grade, hormone sensitive): excellent
prognosis
Type-2 (high grade, hormone independent): poor
outcome.

Conclusions
Surgery is the primary modality; surgical staging
offers the opportunity for the most accurate
assessment of occult extra-uterine disease including
nodal metastases.
Nodal metastasis is the most important risk factor.
The likelihood of nodal metastasis increases with the
extent of disease and tumor grade.
Adjuvant Rx is needed in high risk cases.

Uterine Sarcomas

Pathological subtypes

Incidence

Leiomyosarcoma
Endometrial stromal tumors

25-30%
10-15%

Endometrial stromal nodule

Endometrial stromal sarcoma-low grade
Undifferentiated sarcoma

Mixed epithelial-mesenchymal tumors

Adenosarcoma
Carcinosarcoma (Mixed Mullerian Tumor)

5%
45-50%

Homologous
Heterologous

Undifferentiated

5%

Management of uterine sarcomas

Surgery is the cornerstone of the treatment.
Total abdominal hysterectomy + B/L SO is the
gold standard.
Debulking surgery in advanced cases.
ESS is hormone dependent so SO is indicated .
High recurrence rates even in early stage disease.
Adjuvant treatment has shown to significantly
improvement in survival.