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Endometrial cancer JNMCH AMU ALIGARH


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Endometrial cancer JNMCH AMU ALIGARH

  1. 1. Dr. Neha Jain Dept. Obs & Gyn Jawaharlal Nehru Medical College & Hospital A.M.U., Aligarh
  2. 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. 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. 4. types TYPE- I :- Estrogen Dependent (Unopposed estrogen) (75-85%)  Perimenopausal age  Hyperplastic endometrium  Carcinoma  Better differentiated  Favourable prognosis Type- II :- Estrogen Independent (15-25%)      African American & Asian women Post menopausal women Atrophic endometrium Carcinoma Less differentiated Poorer diagnosis
  5. 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. 6. Corpus cancer syndrome Corpus cancer obesity
  7. 7. Risk also increases with : > Duration of therapy > Cumulative dose
  9. 9. -II <5% of endometrial cancer Hereditary non polyposis colorectal cancer syndrome (HNPCC). Autosomal Dominant disorder Germline mutation in mismatch repair gene, MLH1, MSH2 & MSH6. Colorectal, endometrial, ovarian, gastric, ureter & skin cancer. 40-60% life time risk of endometrial and colorectal cancer. Cancer tends to occur in premenopausal age. Life time risk of ovarian cancer-10-12%.
  10. 10. Preventing factors Oral contraceptive pills1 yr. of use confers 30-50% reduced risk Risk reduction is upto 10-20 yrs. Progestin component has chemo protective role Progesterone IUCDs confers long term protection. Earlier age of menopause Smoking Factors decreasing estrogen.
  11. 11. Screening tests  Pap smear  Progesterone challenge test  TVS  Endometrial biopsy  VABRA or Pipelle
  12. 12. Screening=???... Disease is not so prevalentPap test: Inadequate Insensitive  Screening test should be:  Acceptable Progesterone challenge test:  Reproducible Inconclusive  Valid (sensitivity) Trans vaginal sonography:  Cost effective Too expensive Invasive  Endometrial biopsy: Too expensive Invasive
  13. 13. The current tests can only detect half of all cases of Ca. endometrium
  14. 14. EARLY DIAGNOSIS & TREATMENT  If a lady comes with:  Premenopausal AUB  Post menopausal BPV  Abnormal perimenopausal BPV  25% of the endometrial cancer occurs premenopausally.  5% under the age of 40 yrs.  Early diagnosis & prompt treatment has high cure rate.
  15. 15. 10% (HNPCC or predisposition for endometrial cancer alone) Autosomal dominant What to do in these patients ??? There are 2 alternativesAnnual pelvic examination, TVS & EB from the age of 30-35yrs. OR Prophylactic TAH & BSO after completion of child bearing (Preferred Alternative)
  16. 16. Classification of endometrial cancer (Histological) Endometroid adenocarcinoma  With squamous differentiation  Villoglandular/ papillary  Secretory Mucinous carcinoma Papillary serous carcinoma Clear cell carcinoma Squamous carcinoma Undifferentiated carcinoma Mixed carcinoma
  17. 17. Differentiation is expressed in grades (which in determined by architectural growth pattern & nuclear features): G1- < 5% of the tumor shows solid growth pattern G2- 6-50% shows solid growth pattern G3- >50% 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. 18. Endometroid adenocarcinoma    ~80% of endometroid carcinoma Composed of glands that resemble normal endometrial gland D/d- Atypical hyperplasiaDifferentiated by presence of invasion.
  19. 19. Endometroid adenocarcinoma
  20. 20. Variants of endometroid ca. Squamous differentiation (15-25%) Villoglandular/ papillary (2%) Secretory (1%)
  21. 21. Mucinous carcinoma 5% of endometrial carcinoma On half of the tumor is composed is composed of cells with intracytoplasmic mucin. Prognosis is good D/d- Endocervical adenocarcinoma
  22. 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. 23. Clear cell carcinoma <5% of the endometrial carcinoma Elderly Mixed histological pattern Cells have Hobnail configuration Prognosis- very poor Survival rate- 33-64%
  24. 24. Squamous carcinoma Rare Often associated with cervical stenosis, chronic inflammation & pyometra. Prognosis- poor Survival rate-36% in stage-I
  25. 25. Simultaneous tumors of endometrium & ovary Most frequent simultaneously occurring genital malignancies Incidence- 1.4-3.8% Both are well differentiated Prognosis -Excellent Mostly postmenopausal C/f : AUB (ovarian ca diagnosed incidentally) 29% of endometroid adeno ca. of ovary have associated endometrial cancer.
  26. 26. Clinical features  Average age of presentation- 60 yrs. Mostly 6th & 7th decades of life. 5% presents premenopausally (Novaks 15 th  ed.) Presenting symptoms: Vaginal bleeding Vaginal discharge (may be purulent) Pelvic discomfort/ pain (due to uterine enlargement due to mass or hematometra or pyometra or extrauterine d/s spread)  < 5% - Asymptomatic
  27. 27. Causes of post menopausal BPV ??? Post menopausal BPV Genital Non-genital Uterine Extra-uterine Endo. Atrophy(60-80%) Estrogen replacement (15-25%) Endo. Hyperplasia (5-10%) Endo. polyp (2-12%) Endometrial Ca (10%) Ca. cervix, vagina & vulva Atrophic vaginitis Traumatic bleeding Urinary Gastro intestinal Hematological
  28. 28. Points never to be forgotten Post menopausal BPV is seen in 3% of the post menopausal patients. Amount & type of bleeding is not important 20% of the cases with post menopausal BPV have significant pathology The primary aim is to exclude Atypical Hyperplasia & Endometrial Carcinoma. It is easier to diagnose than to exclude
  29. 29. History &Physical examination History: Obesity, Diabetes, Hypertension, bladder & bowel symptoms Gen. Examination: Weight LN enlargement (Inguinal, abdominal) Breast examination P/A exam: +ve in advanced disease Ascites Hepatic or omental metastasis Pelvic exam: Vaginal introitus, sub urethral area, vagina, cervix P/V exam., P/R exam. (uterus, adenexa, parametrium, cul-de-sac)
  30. 30. investigations Routine investigations Transvaginal sonography* Office based endometrial biopsy (VABRA or Pipelle)* Endocervical curettage (in suspected cervical pathology) Only used if there is: Hysteroscopy Cervical stenosis Dilatation & Curettage Recurrence of bleeding after –ve OBEB Inadequate sampling in specimen
  31. 31. Pre treatment evaluation Examination: Routine investigations: ECG Chest X-ray CA-125- ↑sed in advanced metastatic Ca. USG & MRI- Degree of invasion Cystoscopy, Colonoscopy, IVP, Barium enema- acc. to symptoms
  32. 32. Surgical Staging Hysterectomy B/L Salpingo-oopherectomy Biopsy of all metastatic deposits Peritoneal fluid cytology Cytology in clockwise fashion Pelvic & Para-aortic LN dissection only in high risk- Tumor size >2cm. Grade-III tumor Non endometroid tumor
  33. 33. Figo 2009 staging Stage I- Tumor confined to corpus uteri IA- No or <50% of myometrial invasion IB- >50% of myometrial invasion Stage II- Tumor invades cervical stroma, but does not extend beyond the uterus 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) Stage IV- Bladder &/or Bowel mucosa &/or distant mets. IVA- Bladder &/or Bowel mucosa IVB- Distant metastasis
  34. 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. 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 <5grade better mm from the Histologic grade If Younger age-is poor with: asso. with MARKERS Inc. tumorMETASTASIS inDeterminesINVOVEMENT Lymphatic the risk of Independent dissemination Proportion ofrisk factor ADNEXAL Non-diploid variableEndometroid subtype serosal myometrial prognostic surface- worse Non stage recurrence prognosis ca. Deep Tumor size Lymphatic early 15% inincreases with:chance tumor early stagein lymph node metastasis Type I- Mutationinc.better ERCorrelated with: lymph prognosis Inc. riskis rate of or PR variablesinc. risk asso. (10%)- +ve tumorOlder pts- More invasion Cx involvement recurrence 6 High predictor of : with: times thereis of Myometrial invasion Strong >2cm.~of80-90% 5 Stage Non/sup. Invasion-18% prognosisRecurrence node metastasis of:PTEN risk ofextension recurrence Cervical developingof nodal High grade genes Lack of spread Lymphatic & ß –catenin Lympho-vascular space invasion yr chancesdifferentiationin PRSignificantly 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 5Diseaseinc.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 involvement Lymph node metastasis Intra peritoneal tumor Hormone receptor status DNA ploidy/ proliferative index Genetic/ molecular tumor marker
  36. 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. 37. treatment Exploratory laparotomy Biopsy of any suspicious lesion TAH-BSO Peritoneal cytology Resect any enlarged LN Selective Pelvic & Para-aortic lymphadenopathy
  38. 38. STAGE-IA Tumor confined to corpus uterus, IA- No or <50% of myometrial invasion GRADE-1,2 No/minimal myometrial invasion OBSERVE OBSERVE 100% 5 yr disease free survival rate GRADE-2,Superficial myometrial invasion GRADE-3,No myometrial invasion VAGINAL IRRADIATION
  39. 39. STAGE-IB Tumor confined to corpus uteri, IB- >50% of myometrial invasion GRADE-3, Any myometrial invasion Deep myometrial invasion PELVIC RADIOTHERAPY & VAGINAL BOOST Stage-I survival rate 5yr 87%
  40. 40. STAGE-II Tumor invades cervical stroma, but does not extend beyond the uterus Cervix spread Radiotherapy PELVIC RADIOTHERAPY & VAGINAL BOOST Survival rate 5yr 76% 4500-5040 cGy. 5-6 wks Vaginal boost 6000-7000 cGy
  41. 41. Positive peritoneal cytology OBSERVE OR PROGESTINS
  42. 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 disease PELVIC RADIOTHERAPY & VAGINAL BOOST Paraaortic lymph node +ve- extended field/whole abdomen radiation Survival rate 5yr 59%
  43. 43. GRADE-3, Any myometrial invasion Deep myometrial invasion Cervix, serosal, vaginal spread Positive pelvic lymph nodes -VE Para-Aortic LN PELVIC RADIOTHERAPY & VAGINAL BOOST +VE Para-Aortic LN EXTENDED FIELD RADIOTHERAPY 4000-5000 cGy
  44. 44. STAGE-IV Bladder &/or Bowel mucosa &/or distant metastasis IVA- Bladder &/or Bowel mucosa IVB- Distant metastasis Eradication of all macroscopic disease Partial Colectomy Partial cystectomy Post op CHEMOTHERAPY (Treatment of choice) Survival rate 5yr 18% + WHOLE ABDOMEN RADIATION 3000 cGy with kidney shielding + 1500 cGy to para aortic LN + 2000cGy to pelvis
  45. 45. Algorithm for management Patient with diagnosed endometrial cancer Primary radiation Pre op evaluation & clinical staging Surgical staging Post op radiation Evaluation of prognostic factors Close follow up Selected therapy (progesterone / chemotherapy)
  46. 46. Follow up  History & Physical examination (Most effective method): 1st 2 yrs.- Every 3-4 mths Then- Every 6 mths  Chest X-Ray: Every year  CA-125: For patients : Who have elevated CA-125 @ the time of diagnosis Have extrauterine disease
  47. 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. 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. 49. Rates of recurrence Rates of recurrence Myometrial invasion <50% >50% Lymph nodes -ve +ve Cervical stromal invasion Stage IV disease II/III disease & >2 risk factors I/II/III disease & < risk factors 4% 28% 2% 31% 31% 63% 21% 1%
  50. 50. Factors affecting prognosis Isolated vaginal recurrence Initially well differentiated tumor Recurrence after 3 years Younger age of recurrence Good prognosis
  51. 51. Clinical features
  52. 52. Treatment Isolated vaginal recurrence External radiation + Brachytherapy Pelvic recurrence radiotherapy + Radical surgical resection + Intra op radiotherapy Metastatic carcinoma Combination chemotherapy Progestin therapy in case of Progesterone receptor +ve tumor
  53. 53. Incidental diagnosis 3 OPTIONS: Factors which would guide: observe Risk of nodal/extrauterine d/s Reoperate for surgical staging Pelvic radiotherapy Tumor grade Depth of invasion Evidence of lymphadenopathy on CT abd. or pelvis Patient willingness
  54. 54. Lets see the mind power
  55. 55. Question 1 Factors which decreases the risk of endometrial cancer? a) Estrogen replacement therapy b) Tamoxifen c) Smoking d) Poly cystic ovarian syndrome e) Diabetes
  56. 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. 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. 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 done b) Ask her to come back if BPV recurs c) Reassure her and give her estrogen cream for LA
  59. 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