1、1Endometrial CancerOB/GYN Hospital Fudan UniversityXin LU, MD, Ph.D.2Endometriod cancer-Contents Incidence Risk factors Classification Symptoms Pathology FIGO Staging Diagnosis Treatment3WHO Cancer Report Global cancer rates could increase by 50% to 15 million by 2020 Endometrial cancer is the 4th m
2、ost common cancer in women New Diagnosed cases: 142,000 Died cases each year: 42,000 incidence 2-3% Average age: 60s4Histologic Types Endometrial Cancers Endometrioid (87%) Adenosquamous (4%) Papillary Serous (3%) Clear Cell (2%) Mucinous (1%) Other (3%)5 Endometrial Cancer:Type I/IIType I Estrogen
3、Related Younger and heavier patients Low grade Background of Hyperplasia Perimenopausal Exogenous estrogenFamilial/genetic (15% ) Lynch II syndrome/HNPCC Familial trendType II (10% ) Aggressive High grade Unfavorable Histology Unrelated to estrogen stimulation Occurs in older & thinner women6Endomet
4、rial Cancer: Risk FactorsRisk FactorsRelative Risk X Obesity 2-5 PCOS 5Estrogen use10-20Nulliparous3Infertility2-3Diabetes/Hypertension1.3-3Nulliparous3Early Menarche (12 y/o)1.5-2Atypical Hyperplasia OC0.3-0.5From: Williams Gynecology 20097Endometrium Carcinoma2009 Classification Stage Characterist
5、icStage I* Tumor confined to the corpus uteri IA* No or less than half myometrial invasion IB* Invasion equal to or more than half of the myometriumStage II* Tumor invades cervical stroma, but does not extend beyond the uterus*Stage III* Local and/or regional spread of the tumor IIIA* Tumor invades
6、the serosa of the corpus uteri and/or adnexae# IIIB* Vaginal and/or parametrial involvement# IIIC* Metastases to pelvic and/or para-aortic lymph nodes#. IIIC1* Positive pelvic nodes IIIC2* Positive paraaortic lymphnodes with or without positive pelvic lymph nodesStage IV* Tumor invades bladder and/o
7、r bowel mucosa, and/or distant metastases IVA* Tumor invasion of bladder and/or bowel mucosa IVB* Distant metastases, including intra-abdominal metastases and/or inguinal lymph nodes 8Stage I(73%)Confined to uterusStage II(11%)Cervix involvedStage III(13%)Uterine serosa, adnexae, positive cytology,
8、vaginal metastases, pelvic/aortic node metastasesStage IV(3%)Bladder, bowel, inguinal node, distant metastasisEndometrial Cancer: FIGO Surgical Stage9Endometrial Cancer Prognosis:Survival by Stage:Stage% 5yr survivalIA91IB88IC81IIA77IIB67IIIA60IIIB41IIIC32IVA20IVB5Survival by Grade:Grade% 5yr surviv
9、al192287374Overall 5Yr Survival 84%Stage and Grade are the most important prognostic factorsAltered oncogene/tumor suppressor gene expression is now being evaluated (molecular staging concept)10 Aggressive Histologic Subtypes (Clear-cell, Serous) Increasing age (over 65) Vascular invasion Aneuploidy
10、 Altered oncogene/tumor suppressor gene expression ( “molecular staging” concept- p53, PTEN, microsatellite instability, MDR-1, HER2/neu, ER/PR, Ki 67, PCNA, CD 31,EGF-R, MMR genes) Race? Endometrial Cancer: Poor Prognostic Factors11Molecular Genetics PTEN mutations: 32% Tumor suppressor gene (chrom
11、 10) Phosphatase Early event in carcinogenesis Associated with: endometrioid histology early stage favorable survival 12Molecular Genetics p53 tumor suppressor gene Cell cycle and apoptosis regulation Most commonly mutated gene in human cancers Overexpression (marker for mutation) Associated with po
12、or prognosis early stage: 10% have p53 mutation advanced stage: 50% have p53 mutation not found in hyperplasias late event in carcinogenesis13Genetic Syndromes: HNPCCHereditary Non-Polyposis Colon CancerLynch II Syndrome Autosomal dominant inheritance MMR (mismatch repair) mutations Genetic instabil
13、ity leads to error-prone DNA replication hMSH2 (chrom 2) hMLH1 (chrom 3) Early age of colon Ca: mean 45.2 years Endometrial Ca: second most common malignancy 20% cumulative incidence by age 70 Earlier age of onset than sporadic cases Other: ovary (3.5-8 fold), stomach, small bowel, pancreas, biliary
14、 tract14Diagnosis of disease: Patient Awareness* More than 95% of patients with Endometrial Cancer report having symptoms Postmenapausal bleeding Menorrhagia Metrorrhagia Bloody Discharge Endometrial biopsy is the main diagnostic tool performed either in the office or via D&C in OR15Uterine Cancer:D
15、iagnosis/Screening Patient Symptoms/Awareness* Cytology Not a satisfactory screening test Sonography Not Cost effective Hysteroscopy Not Cost effective Histology Secondary to symptoms (not as a screening test)16Endometrial Cancer:Transvaginal Ultrasound Screening17Endometrial Cancer:Transvaginal Ult
16、rasound Screening18Endometrial Cancer:Transvaginal Ultrasound Screening19 Normal endometrial stripe: Postmenopausal4- 8 mm Postmenopausal on HRT 4- 10 mm U/S for Detection of any uterine pathology Sensitivity: 85-95% Specificity: 60-80% PPV 2-10% NPV 99%Summary: Endometrial Cancer:Transvaginal Ultra
17、sound Screening20Hysteroscopy Not satisfactory for screening testStudies of the efficacy of hysteroscopy as a diagnostic tool vary widelySensitivity reported ranging from 60-95% compared to D&C obtained at the same timeSpecificity 50-99%2122Hysteroscopy and Positive Cytology?Studies have been mixed:
18、Some studies suggest an increase in positive peritoneal cytology seen at staging laparotomy in patients who have had hysteroscopyOther studies have failed to find a difference in positive cytology in patients diagnosed via hysteroscopy as compared to office biopsy or D&C23Hysteroscopy Not satisfacto
19、ry Too much cost and risk to be used as a screening test. Useful for evaluation of abnormal uterine bleeding where office biopsy is unrevealing. Use in conjunction with uterine curettage Useful to see and resect polyps and small submucous fibroids Useful to perform directed biopsy of small lesions.2
20、4Endometrial Cancer:Who Needs an Endometrial Biopsy? Postmenopausal bleeding Perimenopausal intermenstrual bleeding Abnormal bleeding with history of anovulation Postmenopausal women with endometrial cells on Pap Thickened endometrial stripe via sonography25Sampling of the Endometrium Office biopsy
21、procedures (Pipelle, Vabra aspirator, Karman cannula) will agree with a D&C performed in the OR 95% of the time Office biopsy has a 16% false negative rate when the lesion is in a polyp or the cancer covers less than 50% of the endometrium Guido et al. J Reprod Med. 1995;40:553 Patients with persist
22、ent PMB after negative office biopsy should have D&C (+/- hysteroscopy) D&C is the gold standard sampling method preoperative D&C will agree with diagnosis at hysterectomy 94% of the time26272829Treatment for Endometrial Hyperplasia without atypia:Progestin therapy continuous or cyclicalChildbearing
23、 age:Progestin dominant OCPs orDepo-Provera 150mg IM q3 months orProvera 10mg po 10 days/month andMay follow with ovulation induction after normal biopsy if pregnancy desiredPeri or Postmenopausal:Provera 20mg po 10 days/month orDepo-Provera 200mg IM q2 monthsRepeat biopsy in 3-4 months30Treatment f
24、or Atypical Endometrial Hyperplasia:23% risk of progression to carcinoma (over 10 years) if untreated.Standard treatment when childbearing is complete is total hysterectomy (abdominal or vaginal)Frozen section to rule out carcinoma (up to 20% have coexisting endometrial cancer)31Treatment for Atypic
25、al Endometrial Hyperplasia: Conservative medical therapy can be attempted in younger patients who request preservation of fertility. D&C prior to initiation of medical therapy to rule out carcinoma Megace 40-80mg/day, Norethindrone acetate 5mg/day Conservative therapy may also be attempted in young
26、patients with early, well differentiated endometrial carcinomas. Megace 120-200mg/day, Norethindrone acetate 5-10mg/day32Endometroid carcinoma, Grading FIGO- Gr 1 - 50% solid tumor NUCLEAR GRADE Size, shape , staining and chromatin, variability, prominent nucleoli. High nuclear grade adds one point
27、to FIGO grade33CA125Chest X-rayMammogramsColon EvaluationOthers as indicatedUterine Cancer: Pre-op Evaluation34Uterine Cancer: Pre-op EvaluationTransvaginal U/S?CT Scan?MRI?35Uterine Cancer: Pre-op Evaluation36Uterine Cancer: Surgical Staging Preoperative preparation Antimicrobial prophylaxis DVT pr
28、ophylaxis Steep Trendelenburg Long instruments available37 Availability of frozen section to determine the extent of staging procedure. Capability of complete surgical staging Capability of tumor reduction if indicatedEndometrial Cancer: Intra-operative Surgical Principals38Endometrial Cancer: Surgi
29、cal Approach TAH-BSO/washings only Endometrioid* Grades 1 and 50% myometrial invasion* or Grade 2 and no or minimal invasion and 50% myometrial invasion Any 2 cm tumor diameter All Serous/clear cell subtype* Pre operative assessment of advanced disease (gross cervical or vaginal dz, etc)*TAH-BSO, wa
30、shings, lymphadenectomy *omental/peritoneal biopsy40Endometrial Cancer: Adjuvant Therapy Brachytherapy External beam radiotherapy Hormonal therapy Cytotoxic chemotherapy Combination therapy41Endometrial Cancer: Recurrence Pelvic examination Pap smears CA125 (high-risk) Chest X-ray (high-risk)42Endom
31、etrial Cancer: Site of RecurrenceIn Radiated PatientsSite%Distant65Pelvic and distant15Pelvis only15Vagina543Endometrial Cancer: Follow-Up 75-95% of recurrences are in first 36 months 60% of patients have symptoms (pain, wgt loss, vaginal bleeding) Rare to cure distant recurrences 50% vaginal recurrences cured
