1、Endometrial CancerOB/GYN Hospital Fudan UniversityXin LU, MD, Ph.D.Endometriod cancer-Contents Incidence Risk factors Classification Symptoms Pathology FIGO Staging Diagnosis Treatment.WHO Cancer Report Global cancer rates could increase by 50% to 15 million by 2020 Endometrial cancer is the 4th mos
2、t common cancer in women New Diagnosed cases: 142,000 Died cases each year: 42,000 incidence 2-3% Average age: 60s.Histologic Types Endometrial Cancers Endometrioid (87%) Adenosquamous (4%) Papillary Serous (3%) Clear Cell (2%) Mucinous (1%) Other (3%). Endometrial Cancer:Type I/IIType I Estrogen Re
3、lated 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 women.Endometri
4、al 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 2009.Endometrium Carcinoma2009 Classification Stage Characteristic
5、Stage 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 th
6、e 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/or
7、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 .Stage I(73%)Confined to uterusStage II(11%)Cervix involvedStage III(13%)Uterine serosa, adnexae, positive cytology, va
8、ginal metastases, pelvic/aortic node metastasesStage IV(3%)Bladder, bowel, inguinal node, distant metastasisEndometrial Cancer: FIGO Surgical Stage.Endometrial Cancer Prognosis:Survival by Stage:Stage% 5yr survivalIA91IB88IC81IIA77IIB67IIIA60IIIB41IIIC32IVA20IVB5Survival by Grade:Grade% 5yr survival
9、192287374Overall 5Yr Survival 84%Stage and Grade are the most important prognostic factorsAltered oncogene/tumor suppressor gene expression is now being evaluated (molecular staging concept). Aggressive Histologic Subtypes (Clear-cell, Serous) Increasing age (over 65) Vascular invasion Aneuploidy Al
10、tered 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 Factors.Molecular Genetics PTEN mutations: 32% Tumor suppressor gene (chrom 10)
11、 Phosphatase Early event in carcinogenesis Associated with: endometrioid histology early stage favorable survival .Molecular Genetics p53 tumor suppressor gene Cell cycle and apoptosis regulation Most commonly mutated gene in human cancers Overexpression (marker for mutation) Associated with poor pr
12、ognosis early stage: 10% have p53 mutation advanced stage: 50% have p53 mutation not found in hyperplasias late event in carcinogenesis.Genetic Syndromes: HNPCCHereditary Non-Polyposis Colon CancerLynch II Syndrome Autosomal dominant inheritance MMR (mismatch repair) mutations Genetic instability le
13、ads 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 tract
14、.Diagnosis 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 OR.Uterine Cancer:Diagnosis
15、/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).Endometrial Cancer:Transvaginal Ultrasound Screening.Endometrial Cancer:Transvaginal Ultrasound Sc
16、reening.Endometrial Cancer:Transvaginal Ultrasound Screening. 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 Ultrasound Screen
17、ing.Hysteroscopy 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%.Hysteroscopy and Positive Cytology?Studies have been mixed:Some studies sug
18、gest 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&C.Hysteroscopy Not satisfactory Too much cost
19、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.Endometrial Cancer
20、: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 sonography.Sampling of the Endometrium Office biopsy procedures (Pipelle,
21、 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 persistent PMB after negati
22、ve 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 time.Treatment for Endometrial Hyperplasia without atypia:Progestin therapy continuous or cyclicalChildbearing age:Progestin dominant OCP
23、s 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 months.Treatment for Atypical Endometrial Hype
24、rplasia: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).Treatment for Atypical Endometrial Hyperplasia: C
25、onservative 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 patients with early, well dif
26、ferentiated endometrial carcinomas. Megace 120-200mg/day, Norethindrone acetate 5-10mg/day.Endometroid carcinoma, Grading FIGO- Gr 1 - 50% solid tumor NUCLEAR GRADE Size, shape , staining and chromatin, variability, prominent nucleoli. High nuclear grade adds one point to FIGO grade.CA125Chest X-ray
27、MammogramsColon EvaluationOthers as indicatedUterine Cancer: Pre-op Evaluation.Uterine Cancer: Pre-op EvaluationTransvaginal U/S?CT Scan?MRI?.Uterine Cancer: Pre-op Evaluation.Uterine Cancer: Surgical Staging Preoperative preparation Antimicrobial prophylaxis DVT prophylaxis Steep Trendelenburg Long
28、 instruments available. 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 Principals.Endometrial Cancer: Surgical Approach TAH-BSO/washings only E
29、ndometrioid* 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, washings, lymphadenectomy *omental/per
30、itoneal biopsy.Endometrial Cancer: Adjuvant Therapy Brachytherapy External beam radiotherapy Hormonal therapy Cytotoxic chemotherapy Combination therapy.Endometrial Cancer: Recurrence Pelvic examination Pap smears CA125 (high-risk) Chest X-ray (high-risk).Endometrial Cancer: Site of RecurrenceIn Radiated PatientsSite%Distant65Pelvic and distant15Pelvis only15Vagina5.Endometrial 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.
