3Recently 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 : CervixWestern countries India1: :8
4Recent years there has been an increase in incidence of Ca endometrium Prolonged life expectancyInjudicious use of oestrogenHigh detection rateIncreasing awareness and screening
5INCIDENCE Peak incidence is 55-70 yrs Perimenopausal 20-25% Women < 45 yrs 5%Women are either nulliparous or of low parityEarly menarche & late menopause is characteristic75% are localised in the uterus when diagnosedPoorly differentiated in post menopausal and well differentiated and curable in young women
7Any 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.
8OestrogensPersistant stimulation of endometrium with unopposed oestrogen(a) Endogenous – PCOD, fibroid uterus, Granulosa cell tumor(b) Exogenous – OC pills, HRTAge 75% occur – in > 60 yrs of age% of post menopausal women are having Ca endometrium
94. Nulliparity and with less children (30% case)5. Late menopause↑ incidence if menses fails to stop after 52 yearsObesitylow levels of sex hormone binding globulin levels and this allows free oestrogen to circulate in the bodyperipheral conversion of oestrogen to oestrone
10Chronic non ovulatory cycles 8. Family history 7. DUBChronic non ovulatory cycles8. Family historyCa endometrium due to genetic predisposition (12-28%)9. Diet rich in fat → HTN – DM →Ca10. Tamoxifenantioestrogenic agent with mild oetrogenic activityProlonged use ↑ incidence
13Can 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.
14Later involves vault by direct spread or suburethral metastasis occurs through retrograde lymphatic or vascular channelSpreads to adnexa,ovaries as well as to pelvic and para-aortic nodesFundal growth spreads to para-aortic lymph nodes via ovarian lymphatics and also to superficial inguinal lymph nodes via round ligament
19GRADINGGrading is based on differentiation, glandular architecture & anaplasia of the cells
20Clinical Features 7-10% are Asymptomatic Post menopausal bleeding – 75% casesPremenopausal – menorrhagia or irregular periodsh/o PCOD / HRT may be elicitedHTN ,obese,DMClinical features of a bulky uterus(due to growth itself,or due to fibroid or pyometra) may not always be presentIn advanced cases cervix is bulky and os patulous with growth protruding through the os,a metastatic vaginal growth is visible near urethra
21INVESTIGATIONS PAP SMEAR ASPIRATION CYTOLOGY Only 50% sensitive and not reliableEndometrial cells reveal large round cells with dark nuclei filling most of the cells.ASPIRATION CYTOLOGYEffective in screening high riskDone with Pipelle curette, Issac aspirator,Vibra aspirator, and Novak curette
22FRACTIONAL CURETTAGE HYSTEROSCOPY 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 evaluatedHYSTEROSCOPYDirect visualisation and biopsyChance of spill of cancer cells into peritoneal cavity limits its use
23ULTRASOUND DOPPLER ULTRASOUND Studying endometrial thickness , detecting polyp and associated ovarian tumour or ovarian metastasisExtension to cervix can also be recognisedPost menopausal women normal endometium should not exceed 4 mm in thickness and 10 mm in perimenopausal womenDOPPLER ULTRASOUNDRevealing a low resistance index of 0.37+/- 0.7 or below is seen in endometrial malignant lesions
24SONOSALPINGOGRAPHY CA-125 CT Detection of endometrial polyp which could be malignantCA-12535 IU/ml significantNot specific for CA endometiumCTStudy extent of spread of lesionlocalises myometrial infiltrationBut pelvic nodes < 1cm cannot be identifiedSuperior to MRI in detecting ascites, bowel and omental metastasis
25MRISuperior to CT in detection of myometrial involvement and nodal enlargement with 90% detection rate without radiation hazardsX-rayLungs & bonePET-CTReveals metabolic activity in tissues and is gold standard for staging
27STAGINGA 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.
28Surgical staging (FIGO) Stage I – Cancer confined to corpus uteriStage I a (G123) – Tumor limited to endometriumStage I b(G123) - Invasion <1/2 myometriumStage 1 c(G123)- Invasion >1/2 myometriumStage II – Tumour involves cervix but doesnot extend beyond uterusStage II a (G123)-Endocervical glandular involvementStage IIb(G123)- Cervical stromal involvementStage III- Local and/or regional spreadStage III a (G123)-Tumor invades serosa or adnexa or +ve peritonial cytologyStage III b(G123)-Vaginal metastasisStage III c(G123)- Pelvic metastasis or paraaortic LNStage IV- Tumour widespreadStage Iv a(G123)-Tumor involve bladder or bowel mucosaStage Iv b (G123)-Distant metastasis intra abdominal or inguinal LN
30MANAGEMENT Pre Op evaluation 1. Surgery Blood, Urea, X-ray 2. Radiotherapy ECG, LFT, RFT, Combined USG, MRI, Ca 1254. ChemotherapySurgery – 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
31Abdomen 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 cytologyAfter hysterectomy cut open uterus and assess myometrial involvement and cervical extension,tumors sizeTumor differentiation by frozen sectionLymph node sampling or lymphadenectomy is dictated by preoperative grading of tumour,histopathology report and myometrial invasion
33Stage I – TAH + BSO Pertoneal washing Omental Biopsy, Pelvic or Para aortic LN sampling followed by irradiation after 4-6 wks after surgeryNo myometrial invasion observation onlyMyometrial invasion <1/2 thickness.Vaginal vault radiation CGY using colpostatsMyometrial thickness >1/2Whole pelvis ext.irradiation with 6000 CGy over 5-6weeks
34L.N. metastasis – whole abdomen irradiation when Pelvic, Common iliac, Para aortic node are involved protecting the liver and kidneysIntracavitary 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
35Vaginal Hysterectomy- If stage I, well differentiated tumor obese with vaginal prolapse ,should also be combined with laproscopic lymphadenectomy or postoperative radiotherapy
36Stage IIPre-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.
37STAGES III & IV Inoperable Treated by brachytherapy followed by external radiationDose – 6000CGy brachytherapy to a depth of 1-1.5cm beneath endometrium and 7000 CGy to vaginal surface with colpostats over hoursAdjuvant chemotherapy and progestogen therapy prolong remission and improve quality of life.
38Chemotherapy Progesterons – Doxorubicin 60mg/m2 Excellent response with well differentiated Ca with adequate oestrogen and progesterone receptors17-alpha Progesterone 1 gm IM weeklyMdPA 1gm 1/m weekly or 200mg orally dailyTamoxifen 10 mg twice daily –reduces oestrogen rcpsTreatment given for 3 months. If responds give for longer period in reduced dosage.ChemotherapyDoxorubicin 60mg/m2With cisplatin and paclitaxel
39Follow upAfter initial therapyEvery 4 months x 2 years6 months x 2 yearsthen annually
40RECURRENT 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 bonesDistal metastasis occurs in those undergone surgery and post op pelvic radiotherapy
41Prognosis Bad Poorly differentiated Ca > Myometrial invasion Advanced stageAdvanced ageAneuploid tumorsNon endometrioid tumors
425 year survivalStage %Stage II -65%Stage III -44%Stage IV -15%