1. Dr. Neha Jain Dept. Obs & Gyn Jawaharlal Nehru Medical College & Hospital A.M.U., Aligarh

2. Learning objectives The learner will be able to understand: The nature of endometrial cancer The various preventable & non preventable risk factors of endometrial ca. The pitfalls in screening of this carcinoma The evaluation & management of a case of endometrial carcinoma. 3. INTRODUCTION In U.S. it is the most common malignancy of the female genital tract. 4th most common cancer after breast, lung &colorectal cancer. 8th most common cause of death from malignancy.Incidence of endometrial cancer is very low in India. Highest in Delhi 4.3/ lac Bangalore 4.2/ lac Mumbai 2.8/ lac 4. types TYPE- I :- Estrogen Dependent (Unopposed estrogen) (75-85%) Perimenopausal age Hyperplastic endometrium Carcinoma Better differentiated Favourable prognosisType- II :- Estrogen Independent (15-25%) African American & Asian women Post menopausal women Atrophic endometrium Carcinoma Less differentiated Poorer diagnosis 5. 21-50 lb over wt.- 3 times >50 lb over wt.- 10 times Most common cause of endogenous production of estrogen (Williams gyne) Coexisting medical condition / sequele- HTN, DM & Gall bladder disease increases risk (Williams gyne) 6. Corpus cancer syndromeCorpus cancer obesity 7. Risk also increases with : > Duration of therapy > Cumulative dose 8. WITHOUT ATYPIA (1%)WITH ATYPIA (8%)WITHOUT ATYPIA (3%)WITH ATYPIA (29%) 9. -II50% shows solid growth pattern If nuclear atypia is present c is inappropriate for the architectural grade raises grade by 1 grade. In endometroid ca. with squamous differentiation, serous, clear cell and squamous ca. nuclear grading takes precedence. 18. Endometroid adenocarcinoma ~80% of endometroid carcinoma Composed of glands that resemble normal endometrial gland D/d- Atypical hyperplasiaDifferentiated by presence of invasion. 19. Endometroid adenocarcinoma 20. Variants of endometroid ca. Squamous differentiation (15-25%) Villoglandular/ papillary (2%) Secretory (1%) 21. Mucinous carcinoma 5% of endometrial carcinoma On half of the tumor is composed is composed of cells with intracytoplasmic mucin. Prognosis is goodD/d- Endocervical adenocarcinoma 22. Serous carcinoma 3-4% of the endometrial carcinoma Elderly Hypoestrogenic women Aggressive Often associated with Lympho-vascular & deep myometrial invasion Prognosis-poor Accounts for 50% of the deaths from endometrial cancer 23. Clear cell carcinoma 2cm. Grade-III tumor Non endometroid tumor 33. Figo 2009 staging Stage I- Tumor confined to corpus uteri IA- No or 50% of myometrial invasionStage II- Tumor invades cervical stroma, but does not extend beyond the uterusStage III- Local &/or regional spread of tumor IIIA- Serosa of uterus &/or adenexa IIIB- Vaginal &/or parametrial involvement IIIC- Pelvic (IIIC1) &/ or Para-aortic LN (IIIC2)Stage IV- Bladder &/or Bowel mucosa &/or distant mets. IVA- Bladder &/or Bowel mucosa IVB- Distant metastasis 34. ROUTES OF METASTASIS Pattern of spread Contiguous extension: Hematogenous: Lymphatic: Peritoneal:Predictors Grade 3 & LVSI Deep myometrial invasion Cervical stromal invasion & positive lymph nodes Stage-IV d/s Stage-II or III d/s with >2 risk factors: Cervical invasion Peritoneal cytology +ve +ve LN Non-endometroid histology 35. Prognostic variables 1) 2) 3)4) 5) 6) 7) 8) 9) 10) 11) 12)13) 14)LYMPH NODE HORMONE RECEPTOR PERITONEAL CYTOLOGY HISTOLOGICAL GRADE AGE Age ISTHMUS & CERVIX METASTASIS & LYMPH-VASCULAR SPACE DNA PLOIDY MYOMETRIAL INVASION STATUS Independent prognostic EXTENSION INDEX GENETIC/MOLECULAR PROLIFERATIVE TUMOR SIZE INVASION Histologic type INTRAPERITONEAL Dependent prognostic variable Stronglyimp. Prognostic factor variables HISTOLOGICALprognosis asso. with : TYPE Strong predictor of Most TUMOR prognostic Independentother asso. Tumor 2cm.~of80-90% 5 Stage Non/sup. Invasion-18% prognosisRecurrence node metastasis of:PTEN risk ofextension recurrence Cervical developingof nodal High grade genes Lack of spread Lymphatic & catenin Lympho-vascular space invasion yr chancesdifferentiationin PRSignificantly asso. with stronger 1 Distanttumor size For everynode inc. Lymph predictor spread Larger Distant in p53, recurrent ca. yr. metastasis Depth II- Mutation level metastasisrecurrence of dissemination of absolute Type themyometrial Higher 7% recurrence of survival rate in rate Isthmus-cervix extension age tumor recurrence Local 5Diseaseinc.survival rate: Deep free recurrence yr. d/s invasioninvasionthe survival Lymphatic p16, e-cadherin genes Deep invasion- 60% receptors better Poor survival recurrence metastasis Distant 54% Peritoneal cytology Inc. risk of recurrence +veprognosis -ve- 90% Adnexal involvementLymph node metastasis Intra peritoneal tumor Hormone receptor status DNA ploidy/ proliferative index Genetic/ molecular tumor marker 36. Principles of treatment Uterus should be removed in all the patients Pelvic LN metastasis is ~36% in Stage-II, so protocol should include removal of them Chances of d/s spread outside the pelvis (Para-aortic nodes, Adnexal structures & upper abd.) is high, there should be evaluation & treatment of extrapelvic disease. 37. treatment Exploratory laparotomy Biopsy of any suspicious lesionTAH-BSO Peritoneal cytologyResect any enlarged LN Selective Pelvic & Para-aortic lymphadenopathy 38. STAGE-IA Tumor confined to corpus uterus, IA- No or 50% of myometrial invasion GRADE-3, Any myometrial invasion Deep myometrial invasionPELVIC RADIOTHERAPY & VAGINAL BOOST Stage-I survival rate 5yr 87% 40. STAGE-II Tumor invades cervical stroma, but does not extend beyond the uterusCervix spread Radiotherapy PELVIC RADIOTHERAPY & VAGINAL BOOST Survival rate 5yr 76%4500-5040 cGy. 5-6 wksVaginal boost 6000-7000 cGy 41. Positive peritoneal cytologyOBSERVEOR PROGESTINS 42. STAGE-III Local &/or regional spread of tumor IIIA- Serosa of uterus &/or adenexa IIIB- Vaginal &/or parametrial involvement IIIC- Pelvic (IIIC1) &/ or Para-aortic LN (IIIC2) Eradication of all macroscopic diseasePELVIC RADIOTHERAPY & VAGINAL BOOST Paraaortic lymph node +ve- extended field/whole abdomen radiationSurvival rate 5yr 59% 43. GRADE-3, Any myometrial invasion Deep myometrial invasion Cervix, serosal, vaginal spread Positive pelvic lymph nodes-VE Para-Aortic LNPELVIC RADIOTHERAPY& VAGINAL BOOST+VE Para-Aortic LNEXTENDED FIELD RADIOTHERAPY4000-5000 cGy 44. STAGE-IV Bladder &/or Bowel mucosa &/or distant metastasis IVA- Bladder &/or Bowel mucosa IVB- Distant metastasis Eradication of all macroscopic diseasePartial Colectomy Partial cystectomyPost opCHEMOTHERAPY (Treatment of choice) Survival rate 5yr 18%+ WHOLE ABDOMEN RADIATION3000 cGy with kidney shielding + 1500 cGy to para aortic LN + 2000cGy to pelvis 45. Algorithm for management Patient with diagnosed endometrial cancerPrimary radiationPre op evaluation & clinical stagingSurgical stagingPost op radiationEvaluation of prognostic factorsClose follow upSelected therapy (progesterone / chemotherapy) 46. Follow up History & Physical examination (Most effective method): 1st 2 yrs.- Every 3-4 mths Then- Every 6 mthsChest X-Ray: Every yearCA-125: For patients : Who have elevated CA-125 @ the time of diagnosis Have extrauterine disease 47. Recurrent disease ~25% of the treated early endometrial cancer recurs. st >50% recurs in 1 2 years~75% recurs in 1st 3 years 48. Points to remember Recurrence is less when the surgery is combined with post op radiation therapy Patient treated with surgery + radiation generally do not have local or pelvic recurrence but have extrapelvic mets. M/C site for mets.- Lung, Abdomen, Lymph nodes (Aortic, Supraclavicular, Inguinal), Liver, Brain & Bone 49. Rates of recurrence Rates of recurrence Myometrial invasion 50% Lymph nodes -ve +ve Cervical stromal invasion Stage IV disease II/III disease & >2 risk factors I/II/III disease & < risk factors4% 28% 2% 31% 31% 63% 21% 1% 50. Factors affecting prognosis Isolated vaginal recurrenceInitially well differentiated tumor Recurrence after 3 yearsYounger age of recurrenceGood prognosis 51. Clinical features 52. Treatment Isolated vaginal recurrenceExternal radiation + BrachytherapyPelvic recurrenceradiotherapy + Radical surgical resection + Intra op radiotherapyMetastatic carcinomaCombination chemotherapyProgestin therapy in case of Progesterone receptor +ve tumor 53. Incidental diagnosis 3 OPTIONS:Factors which would guide:observeRisk of nodal/extrauterine d/sReoperate for surgical staging Pelvic radiotherapyTumor grade Depth of invasion Evidence of lymphadenopathy on CT abd. or pelvisPatient willingness 54. Lets see the mind power 55. Question 1 Factors which decreases the risk of endometrial cancer? a) Estrogen replacement therapy b) Tamoxifenc) Smoking d) Poly cystic ovarian syndrome e) Diabetes 56. Question 2 A lady is diagnosed of endometrial cancer which is extending to the cervical stroma and her pelvic lymph node biopsy came to be +ve. In which stage you would like to keep her? a) Stage IA b) Stage II c) Stage IIIA d) Stage IIIC 57. Question 3 A 50 yr old lady has been diagnosed of having papillary serous carcinoma endometrium and another lady is diagnosed of having mucinous carcinoma. Both are in stage II. Which lady is going to survive more after therapy? 58. Question 4 In your OPD-8 if a post menopausal lady since 11yrs. gave history of spotting last night. After history & examination you came to know that there are no risk factors of endometrial cancer & the cervix is also healthy but atrophic. Now what you will do? a) Ask her to get a TVS doneb) Ask her to come back if BPV recurs c) Reassure her and give her estrogen cream for LA 59. Question 5 If a lady is diagnosed to have ca endometrium which has spread to the endocervical glands. Under which stage you would like to keep her? a) Stage IA b) Stage IB c) Stage II d) Stage IIIA