ENDOMETRICAL CARCINOMA

Govt Medical CollegeThrissur,Kerala

IMPORTANCE???

Recently emerged as the more frequently encountered gynecological cancer accounting for 20-25% of all genital cancers in developed countries.

In India incidence is low as 5-7% of all genital cancers,continues to be the second most common of all genital cancers.

Incidence of Ca Endometrium : Cervix

Western countries India1:1 1 :8

Recent years there has been an increase in incidence of Ca endometrium

1. Prolonged life expectancy2. Injudicious use of oestrogen3. High detection rate4. Increasing awareness and screening

INCIDENCE Peak incidence is 55-70 yrs Perimenopausal 20-25% Women < 45 yrs 5% Women are either nulliparous or of low

parity

Early menarche & late menopause is characteristic

75% are localised in the uterus when diagnosed

Poorly differentiated in post menopausal and well differentiated and curable in young women

RISK FACTORS

Any factor that increases the exposure of endometrium to unopposed or high osetrogen level, both endogenous and exogenous , increases the risk .

Also linked to the dose and duration of exposure and the risk persists for 10 yrs after hormone exposure.

1. Oestrogens

Persistant stimulation of endometrium with unopposed oestrogen

(a) Endogenous – PCOD, fibroid uterus, Granulosa cell tumor

(b) Exogenous – OC pills, HRT

2. Age 75% occur – in > 60 yrs of age

3. 10 % of post menopausal women are having Ca endometrium

4. Nulliparity and with less children (30% case)

5. Late menopause↑ incidence if menses fails to stop

after 52 years

6. Obesity low levels of sex hormone binding globulin

levels and this allows free oestrogen to circulate in the body

peripheral conversion of oestrogen to oestrone

7. DUBChronic non ovulatory cycles

8. Family history Ca endometrium due to genetic

predisposition (12-28%)

9. Diet rich in fat → HTN – DM →Ca

10. Tamoxifen antioestrogenic agent with mild

oetrogenic activityProlonged use ↑ incidence

I

PATHOLOGY

Can be localized or diffuse

Appear as nodule,a polyp,or as a diffuse lesion involving entire uterine cavity.

Extends to endocervix in advanced stage and invades myometrium to varying degree.

Later involves vault by direct spread or suburethral metastasis occurs through retrograde lymphatic or vascular channel

Spreads to adnexa,ovaries as well as to pelvic and para-aortic nodes

Fundal growth spreads to para-aortic lymph nodes via ovarian lymphatics and also to superficial inguinal lymph nodes via round ligament

HISTOLOGY

• Microscope1. Adeno Ca (Endometrioid Ca) -80%2. Adeno squamous Ca3. Papillary Ca4. Clear cell adeno Ca5. Mucinous adeno Ca6. Primary squamous cell Ca7. Mixed variety

GRADINGGrading is based on differentiation, glandular architecture & anaplasia of the cells

Clinical Features 7-10% are Asymptomatic

Post menopausal bleeding – 75% cases

Premenopausal – menorrhagia or irregular periods

h/o PCOD / HRT may be elicited

HTN ,obese,DM

Clinical features of a bulky uterus(due to growth itself,or due to fibroid or pyometra) may not always be present

In advanced cases cervix is bulky and os patulous with growth protruding through the os,a metastatic vaginal growth is visible near urethra

INVESTIGATIONS

PAP SMEAR

Only 50% sensitive and not reliable

Endometrial cells reveal large round cells with dark nuclei filling most of the cells.

ASPIRATION CYTOLOGY

Effective in screening high risk

Done with Pipelle curette, Issac aspirator,Vibra aspirator, and Novak curette

FRACTIONAL CURETTAGE

Histological study of endocervical scraping before dilating the cervix , followed by cervical dilatation and curettage from the isthmus, body and fundus of the uterus separately, so that extent can be evaluated

HYSTEROSCOPY

Direct visualisation and biopsy

Chance of spill of cancer cells into peritoneal cavity limits its use

ULTRASOUND

Studying endometrial thickness , detecting polyp and associated ovarian tumour or ovarian metastasis

Extension to cervix can also be recognised

Post menopausal women normal endometium should not exceed 4 mm in thickness and 10 mm in perimenopausal women

DOPPLER ULTRASOUND

Revealing a low resistance index of 0.37+/- 0.7 or below is seen in endometrial malignant lesions

SONOSALPINGOGRAPHY

Detection of endometrial polyp which could be malignant

CA-125

35 IU/ml significant

Not specific for CA endometium

CTStudy extent of spread of lesionlocalises myometrial infiltrationBut pelvic nodes < 1cm cannot be identifiedSuperior to MRI in detecting ascites, bowel and omental metastasis

MRI

Superior to CT in detection of myometrial involvement and nodal enlargement with 90% detection rate without radiation hazards

X-ray Lungs & bone

PET-CT

Reveals metabolic activity in tissues and is gold standard for staging

DIFFERENTIAL DIAGNOSIS

DUBSenile vaginitisVulval growthVaginal growthCervical lesionsUterine tumourTB endometritis Atrophic endometritis Atypical hyperplasia and polypi

STAGING

A staging laparotomy is recommended through a midline lower abdominal incision,collect any peritoneal ascitic fluid or washings for cytology ,complete abdominal exploration followed by total abdominal hysterectomy along with bilateral salpingo-oophorectomy and pelvic and para-aortic lymph node sampling.

Surgical staging (FIGO)Stage I – Cancer confined to corpus uteri

Stage I a (G123) – Tumor limited to endometrium

Stage I b(G123) - Invasion <1/2 myometrium

Stage 1 c(G123)- Invasion >1/2 myometrium

Stage II – Tumour involves cervix but doesnot extend beyond uterus

Stage II a (G123)-Endocervical glandular involvement

Stage IIb(G123)- Cervical stromal involvement

Stage III- Local and/or regional spread

Stage III a (G123)-Tumor invades serosa or adnexa or +ve peritonial cytology

Stage III b(G123)-Vaginal metastasis

Stage III c(G123)- Pelvic metastasis or paraaortic LN

Stage IV- Tumour widespread

Stage Iv a(G123)-Tumor involve bladder or bowel mucosa

Stage Iv b (G123)-Distant metastasis intra abdominal or inguinal LN

Pre Op evaluation1. Surgery Blood, Urea, X-ray2. Radiotherapy ECG, LFT, RFT, 3. 3.Combined USG, MRI, Ca 1254. Chemotherapy

Surgery – Is the mainstaySurgical staging,TAH+ BSO +

pelvic as well al para aortic lymph node sampling remains the cornerstone in the Mx of early endometrial cancers

MANAGEMENT

Abdomen is opened by a vertical incision that allows a thorough intra-abdominal exploration

Peritoneal washings are obtained from sub diaphragmatic area, paracolic gutters and the pelvis and sent for cytology

After hysterectomy cut open uterus and assess myometrial involvement and cervical extension,tumors size

Tumor differentiation by frozen section Lymph node sampling or lymphadenectomy is

dictated by preoperative grading of tumour,histopathology report and myometrial invasion

Stage 0 –Simple endometrial Hyperplasia – 10-20%

Atypical hyperplasia – 70%Elderly

TAH + BSO (with removal of ovaries)Prolonged Progesterone therapy

Young PatientProgesterone therapy (30-40mg

medroxyprogesterone acetate for 6-12 months Life long follow up

Levonorgestrel containing IUCD

Stage I – TAH + BSO Pertoneal washing Omental Biopsy, Pelvic or Para

aortic LN sampling followed by irradiation after 4-6 wks after surgery

No myometrial invasion observation only

Myometrial invasion <1/2 thickness.

Vaginal vault radiation 6000-7000CGY using colpostats

Myometrial thickness >1/2 Whole pelvis ext.irradiation

with 6000 CGy over 5-6weeks

L.N. metastasis – whole abdomen irradiation when Pelvic, Common iliac, Para aortic node are involved protecting the liver and kidneys

Intracavitary radiation followed by extended hysterectomy after 48 hours in cases of

-Highly Anaplastic tumor-Uterine cavity considerably enlarged-Growth extending to cervix-Deeply invasive cancer

Vaginal Hysterectomy- If stage I, well differentiated tumor obese with vaginal prolapse ,should also be combined with laproscopic lymphadenectomy or postoperative radiotherapy

• Stage II

Pre-op intracavitary radiotherapy followed by TAH +BSO +Pelvic node dissection

(OR) Wertheims Hysterectomy followed by ext.radiotherapy,

if LN involved dose of 5000CGy over 5 weeks.

STAGES III & IV

Inoperable

Treated by brachytherapy followed by external radiation

Dose – 6000CGy brachytherapy to a depth of 1-1.5cm beneath endometrium and 7000 CGy to vaginal surface with colpostats over 48-72 hours

Adjuvant chemotherapy and progestogen therapy prolong remission and improve quality of life.

Progesterons – Excellent response with well differentiated Ca with adequate oestrogen and progesterone receptors 17-alpha Progesterone 1 gm IM weekly

MdPA 1gm 1/m weekly or 200mg orally daily

Tamoxifen 10 mg twice daily –reduces oestrogen rcps

Treatment given for 3 months. If responds give for longer period in reduced dosage.

Chemotherapy

Doxorubicin 60mg/m2

With cisplatin and paclitaxel

Follow upAfter initial therapy Every 4 months x 2 years6 months x 2 yearsthen annually

RECURRENT GROWTHS

Occurs within 2 yrs in 50%

3 yrs in 75%

Metastasis occurs in vaginal vault , lateral pelvic walls lymph nodes, lungs, liver, brain and bones

Distal metastasis occurs in those undergone surgery and post op pelvic radiotherapy

Prognosis BadPoorly differentiated Ca> Myometrial invasion Advanced stageAdvanced ageAneuploid tumorsNon endometrioid tumors

• 5 year survival

Stage 1 - 82%

Stage II -65%

Stage III -44%

Stage IV -15%

That’s all….