The uterus is a hollow, pear shaped organ with thick musc- ular wall (L 8cm,W 5cm ) in young nulliparous adult. IsDivide into the fundus,body,and cervix. The fundus is thePart lies above the entrance of the uterine tubes. The bodyIs the part lies below the entrance of the uterine tube isNarrowing inferiorly to open in the cervix by the internal os.Related interiorly to the uterovesical pouch and superiorSurface of the bladder. Posteriorly to the rectoutrine pouchLaterally to the broad ligament and uterine artery andVein.
The uterus is covered with peritoneum until the internalOs. The uterus is lining by the mucous membrane.Lymph drainage;-From the funds go to the para-oartic nodes at the L1.Lymph from the the body and cervix d go to the internalAnd external iliac nodes
New case in USA in 2010 is 42.160. it is the 4th most .Common cancer in women and ranks 8th among causeOf cancer death . It is the most common gynecologicMalignancy .Risk factors ;- 1) age ;-postmenopausal (55--85yrs)Incidence rate higher than 95 per100,000 in age 65-80Yrs 2)endogenous estrogen exposure ;-early menarche/nulliparity/infertility/late menopause/estrogen producing tumor . 3) exogenous estrogen;-hermonal replacementTherapy tamoxifen
4) past medical history;- hypertension diabetes mellitus 5) family history ;-less than 1% of endometrial ca- is due to familial factors . 6) Genetic factors ;- mutations in the MLH1 or MSH2Gene cause of defect in HNPCC (lynch syndrome11) have 20% risk to developing endometrial cancer before 50 and 60% risk after the age 60 yrs
The majority of edometrial cancer is adenocarcinomas which include serous/mucinous/clear cell/mixed cell. The epithelial non adenocarcianom include ;-squamous cell carcinoma /transitional cell carcinomaSmall cell carcinoma /un differentiated carcinoma .The mesenchymal originated tumor of the uterus include;- --smooth muscle tumor;- -leiomyoma -leiomyosarcomaOf un certain malignant potential.Stromal tumor ;- sarcoma /nodule/undifferentiated sarcoma
Clinical presentation;- vaginal bleeding in unexpectedPostmenopausal lady (menorrhagia/metrorrhagia ).Profuse watery discharge is another presentation .Attention should be paid to the duration and severity ofThe symptoms. Screening for risk factors include,Obesity,hypertension,diabetic,history of estrogen use,History of endometrial atypical hyperplasia. History ofBreast cancer and treatment with tamoxifen,
Examination ;-Examination should be performed with attention to theThe abdomen,plevic (examination of the cervix andvagina).Palpation of the lymph nodes in the inguinal and supra-Clavicle regions . Then examining for metastsis disease(palpation of the bone to the pain/kidney/nerologicalsign ).Lab test;- CBC /blood chemistry/RFT/LFT/alkaline phos-Phatase.Imaging include;- transvaginal US /abd-pelvic CT to assessExtra-uterine disease
Endometrial cancer suspected Complete history and physical exam ± Trans-vaginalEndometrial biopsy /US NON diagnosis Dilatation and curettage Pre-operativeobserve assessment hysteroscopy Diagnosis of endometrial cancer
Endometrial cancer staging is depend on the pathologic criteria the recent change in the Federation of Gynecology and Obstetrics(FIGO)And American Joint Committee on Cancer(JOCC)were made to include coincide with prognosis
FIGO stagi 20092008 TNM nggroup T N M Description 1A T1a 0 0 Limited to endometrial or invades >1/2 of myometrium 1B T1b 0 0 Invades ½ or more of the myometrium 11 T2 0 0 Invades cervical stromal tissue but not beyond uterus 111A T3a 0 0 Involve serosa and /or adnexa 111B T3b Vaginal involvement or parametrial involvement T1-3 1 0 Metastasis to pelvic LNs111C1 T1-3 2 0 metastasis to para aortic LNs111C2 1VA T4 any 0 Invade bladder mucosa or bowel mucosa 1VB any any 0 Distant metastasis
Survival rate at 5yreas,based on stage classificationExtent of disease at 5-yrs survival ratediagnosisLocalized 96%Regional 68%Distant 24%All stage 83%
Prognosis factors ;-survival strongly depend on the stage at diagnosis other factors include ;-1) Advanced age associated with higher chance of recurrence2) Higher grade;- associated with higher chance of recurrence .3) Aggressive histology as clear cell adenocarcinoma,Un differentiated papillary serous carcinoma areAssociated with worse prognosis 4) depth of myometrial invasion 5)lymph vascular space invasion
The stander treatment is total extrafascial hysterectomy with bilateral salpingo-oophorectomy,peritoneal cytology and pelvic / Para-aortic lymph nodes dissection traditionally done through vertical midline incision laparoscopic tech-Has recently been used . Depending on the pathologicalData .high risk patients (↑rate of local recurrence) adjuvant radiation therapy will recommended to these patients .Systemic therapy is used inlocoregional advanced/Recurrence or metastatic disease
Treatment of early stage endometrial cancer;-1ry treatment is surgical resection, then pathologic specimen is examined for risk factor to determined a patient risk of loco regional recurrence according toWhich determine adjuvant therapy
Total extrafascial hysterectomy +bilateral salpigo- oopharectomy Low risk Intermediate risk High -risk Vaginal brachy- EBRT + vaginalobservation Therapy or brachytherapy EBRT± VB Algorithm for treatment of early stage edometrial cancer
as seen in the previous algorithm there is mixed recom-Mendation to treatment options for intermediate riskGroup of patients these is due to patients and diseaseRelated factors GOG identifies these high –intermediateSubgroup in which the adjuvant therapy is of benefitRisk factors ;- 1) grade 2/3 histology 2) lymphvascular invasion 3) outer 1/3 myometrial
Treatment of early stage endometrial cancer FIGO Grade stage 1 11 111 1A observation Observation or VB VB or EBRT with or Without VB 1B VB or EBRT with VB or EBRT with EBRT with VB or or Without VB Without VB 11 EBRT with VB EBRT with VB EBRT with VB VB;-vaginal brachytherapy EBRT ;-external beam radiation therapy
Locoregionally advanced endometrial cancer;-These patients usually treated by surgery followed byAdjuvant radiation. Para-aortic irradiation incase wherePelvic or para aortic LNs +ve.vaginal brachytherapy isOften is added due to ↑ risk of vaginal cuff recurrence.
Chemotherapy and hormonal therapy ;- for stage 111,1vAfter surgery the tumor mass should be examined toER,PR level (benefit of hormonal treatment).Hormonal therapy :- response occur in 20-40% of patientsDuration 1yr (improve out come) .the most frequentlyusedDrugs:- 1) medroxyprogesterone (Depo-Provera). 2)megestrol acetate. 3) tamoxifen.Chemotherapy :- regime containing platinum anddoxorubicin used (response up to 40%,↑survival,PFS asCompared to WAI*) (GOG122).The EORTC study to the stage1-111 (high risk) reportedimproved 5 yrs PFS of 80% with adjuvantCH-RT over 75% to the RT alone
Trial Description Number of patients =388 stage 111– 1v endometrial ca- After TAH/BSO surgical staging and <2cm residual tumorGOG Randomized to whole abdominal irradiation (WAI)122 Versus doxorubicin- cisplatin(AP) chemotherapy WAI =30 GY in 20 fr AP/PA +boost to pelvic/Para aortic LNs to 15 GY in 8 fr . PA every 3 week for 8 cycles . 5 yrs PFS→ 38% for WAI versus 50% for AP . 5yrs OS was 42% for WAI versus 52% for AP . Recurrence after WAI was 54% versus 50% after AP . AP had more grade 3-4 hematological and gastroin- Testinal toxicity *chemotherapy improve PFS and OS as compared To WAI for stage 111&1v patients after surgical resection
Adjuvant external radiation therapy ;-four randomized trials that evaluated adjuvant EBRT versus observation in the earlyStage endometrial cancer (after surgery).these is local control benefit but does notTranslate in to survival benefitstudy year No of eligibility Treatment VB Randomize Vaginal/ OS number LN d to EBRT pelvic recurren ceNor- 1980 540 1B-1Cb NO yes 40 GY 2 87 NSwegian Observatio 7 90 NS n-PORTE 2000 715 1B-G2-3 NO NO 46 GY 4 81 NSC 1CG1-2 observatio 14 85 NS nGOG- 2004 392 1B-1C yes NO 50.4GY 3 92 NS99 Occult observatio 12 86 NS 11 nMRC 2009 906 1A- 30% 52 40-46 GY 3 85 NSASREC 1B,G3 % obsession 6 85 NS&NCIC SerousCTG EN papillary
Medically inoperable:- EBRT to the pelvis (include LNs)And other involved area (45-50 GY ) followed by intra-Cavitary BT (6GY X 3HDR) for early stage but inoperableFor medical reason (survival rates of 80% -85% at 5 yrs).In definitive RT to the uterus we need to the intra-uterineSources and upper vaginal sources.Unrespectable disease:- treated with EBRT and BT as aboveIn medical inoperable disease .Recurrence:- if no prior RT→EBRT and BT boost→60-70 GY. BT can be used in selected previously irradiatedPts.CTH can be conceder in metastasis and recurrence diseaseSpecially if not previously received
treatment of less common histological types:-1)papillary/serous/clear cell:- conceder CTH or RT to theStage 1B,1C,11, and debulked stage 111,1v . Cth± RT.While stage 1A treated by surgery.CTH include carboplatin/paclitaxel/platinum.carcinosarsarcima:- surgery –then op-RT for (sarcoma/Leimyosarcoma,and carcinosarcoma) to improve localRecurrence LC . Consider CTH for high gradeundifferentiated sarcoma and leiomyosarcoma.GOG150→comparing RT(WAI) with CTH (cisplatin-Ifosphamide)→ CTH delay the recurrence more thanRT. These is more anemia/neuropathy in CTH.
RADIATION THERAPY TECHNIQUESSimulation and field arrangement;-CT should performed (2.50-5mm) from the top of the L4 toThe lesser trochanters of the femurs. Aides used during theSimulation include Foley catheter, intravaginal marker or intr-avenous contrast .organ at risk include ;- OAR dose limitation Bladder V80 <15% / V75<25% /V70,V65 <50% Rectum V50<50% / V60<35% /V65<25 , V70<20% ,V75<15% Small intestine TD5/5; 45 GY ,V45<10% /// 150ml <40 GY Femoral head Max <40 GY
Field border used in the( EBRT) treatment of the of endo-Metrial cancer . fields borders Ap/PA superior op of L5 inferior ;-bottom of the obdurate foramina lateral ;-2 cm lateral to bony margin of the pelvic inlet lateral superior and inferior as in AP/PA fields . anterior ;-in front of the pubic symphysis Posterior ;-S2-S3
3- Dimensional conformal Radiation Therapy and Intensity-modulated Radiation therapy and target delineation ;-the benefit of these techniques in sparing of the normalTissues .Target volume ;- GTV;- entire uterus (inoperable cases) . CTV ;- vaginal cuff,obturator lymph nodes and external/Internal/common iliac lymph nodes .PTV ;- CTV +0,5-1.0 cm .Organ at risk should be contoured are bladder/small intestine/rectum/femoral head
Brachytherapy ;-Is used to delivery of high dose to the vagina while minimizing the dose to the organ at risk . The vaginalCylinder is the most common applicator used . The radiation is delivered into ;- 1) low-dose-rate (LDR) . 2)high dose rate(HDR) .The LDR to the surface is 50-60 GY over 60-70 hrs whenUsed alone . The dose is reduced to25-30 GY whenCombined with EBRT .
HDR dose as prescribed by the American BrachytherapySocietySuggested dose of HDR alone for adjuvant endometrial ca Number of HDR HDR dose/fraction (GY) Dose- specific point fractions 3 7.0 0.5-cm depth 4 5.5 0.5-cm depth 5 4.7 0.5-cm depth 3 10.5 vaginal surface 4 8.8 vaginal surface 5 7.5 vaginal surface
Suggested dose of HDR when used with45 GY EBRT forAdjuvant endometrial cancer ;- Number of HDR HDR Dose /fraction Dose-specific-point fractions 2 5.5 0.5 cm depth 3 4.0 0,5cm depth 2 8.0 vaginal surface 3 6.0 vaginal surface
Radiotherapy- induced side effects:-Pelvic radiation lead to clinically significant side effectSpecially when combined with other modalities ofTreatment as:- 1) RT + surgery→ lower limb lymphedema 2) RT + CTH→ hematological and gastrointestinal toxici-Ties.Long term side effect include:- 1)Urinary and rectal inflammation and fistula aftermonths or years. 2) narrowing or scarring of the vagina 3)Pain or bleeding during with bowel movement.
Follow up ;-Follow up schedule and examination ;- schedule frequency first follow up 4-6 weeks after radiation therapy years 0--2 every 3—4 months years 3--5 every 6 months years 5+ annually
Examination ;- History and examination complete history and physical exam- ination laboratory tests vaginal cuff cytology imaging studies chest x ray (if clinically indicated) CT of the abdomen and pelvic if clinically indicated .