Gynecologic Oncology Pre invasive vulvar, vaginal, & cervical disease Vulvar Cervical Endometrial Uterine Sarcoma Fallopian Tube Ovarian GTD Gynecologic Oncologist Surgery Chemotherapy Radiation Therapy Hormonal Therapy Immunotherapy Cervical 14,500 new cases per year in U.S. 5,500 deaths Peak age 47 years Most common gynecological cancer world wide Etiology and Risk Factors Sexual activity HPV 16,18,31,33,35 subtypes Cigarette smoking Immune system alterations Treatment Depends on stage, disease bulk, patient characteristics & preference Radical pelvic surgery Radiation +/- chemotherapy 1
Clinical staging of cervical cancer Treatment Selection Stage Tumor volume Complicating medical conditions Known extrapelvic disease (pelvic & PA nodal mets Age & body habitus Surgery vs. Radiation Therapy for Stage I & IIA Disease Cure Rate is Equal Advantages Applies to all patients Survival equal to surgery for early stage disease Mainly outpatient therapy Cervical cancer Radiation Therapy Disadvantages Bladder & bowel injury (2-6%) Vaginal stenosis Sexual dysfunction Ovarian failure Delayed complications Prognosis Clinical Stage Lesion size Depth of cervical invasion Angiolymphatic space involvement Nodal metastasis Predominately squamous cell histology (85-90%) Viral & venereal association Definitive diagnosis of microinvasion is made on cone biopsy Microinvasive carcinomas (SGO def) may be treated by less than radical surgery Stage I thru IIA are equally treated by pelvic radiation or radical surgery Endometrial Most common female pelvic malignancy 40,000 new cases per year 7,000 deaths Ranks 4th behind lung, breast, & colon 75% are postmenopausal 75% are clinical stage I 75% overall 5 year survival 2
Endometrial Post-menopausal bleeding Peri-menopausal bleeding Irregular pre-menopausal bleeding Endometrial Role of surgery Definitive treatment (TAH) Staging and nodal biopsies / lymphadenectomy Control of pelvic disease and hemorrhage FIGO Surgical Staging of Endometrial Stage IA: Tumor limited to endometrium Stage IB: Invasion < 50% of myometrium Stage IC: Invasion > 50% of myometrium Stage IIA: Endocervical gland invovlement Stage IIB: Cervical Stromal involvement FIGO Surgical Staging of Endometrial Stage IIIA: Tumor invades serosa, adnexa, or positive cytology Stage IIIB: Vaginal metastases Stage IIIC: Mets to pelvic or PA nodes Stage IVA: Bladder or rectal involvement Stage IVB: Distant mets, intra-abdominal or inguinal nodes Vulvar 0.3% of all female cancers 3-5% of all female genital malignancies 85-95% squamous cell 3,000 new cases per year in U.S. 3
Vulvar Clinical Presentation Itching, soreness, bleeding Lump or lesion Patient delay in seeking treatment Physician delay in making diagnosis Vulvar Radical vulvectomy, bilateral inguinal / femoral lymphadenectomy Defines extent of disease (stage) Definitive treatment for most patients The Diagnostic Dilemma of the Adnexal Mass The Fear of Adnexal Mass Ovarian Masses Adnexal Mass Non Gynecologic Diverticulitis Ileitis Appendicitis Colon Urologic Gynecologic Ovarian Uterine Fallopian Tube Lymphatic Pregnancy Infectious Functional Cysts Endometriomas Neoplastic What is the suspicion of malignancy? Is surgery indicated? Choice of surgical technique & incision? Should oncologist be involved? Pre-operative counseling and plan? 4
Adnexal Mass Oncology Consult Suggested Elevated CA-125, LDH, AFP, HCG Complex US findings Premenarchal Ascites Fixation Prior cancer diagnosis Ovarian Epithelial Germ Cell Stromal Carcinomas Metastatic Ovarian : Histologic Distribution Ovarian Germ Cell Tumors 20-25% of ovarian neoplasms Most frequent in late teens or early twenties Fertility concerns Often present with acute pain Confused with appy or ectopic Chemo sensitive Almost always unilateral except dysgerminoma Benign Dermoid Ovarian Germ Cell Tumors Malignant Dysgerminoma Immature teratoma Endodermal sinus tumor Embryonal carcinoma Ovarian Stromal Tumors Benign Fibroma Thecoma Lydig cell Malignant Granulosa cell Sarcoma 5
Epithelial Ovarian Leading cause of death from Gynecologic cancer 2008 35,000 new cases 16,000 deaths Lifetime risk 1 in 70 5% hereditary Overall 5 year survival 44% Epithelial Ovarian Age - Primarily postmenopausal Race - Caucasian > Black Geography - European Reproduction Low Parity Breast feeding OCP (protective) ERT (no effect) Ovarian Signs & Symptoms Early Usually no symptoms Incidental mass found on routine exam Late Abdominal bloating Nausea, Vomiting Bladder and rectal symptoms 6
Surgery in Ovarian Definitive Diagnosis Determine Extent of Disease Cytoreduction Second Look Laparotomy Palliation Suspected Ovarian cancer Pre-operative evaluation Ultrasound? Colonoscopy or BE? CT Scan? Tumor markers? CXR Mammogram (>35yrs) Counseling Staging of Ovarian Adequate incision Aspiration of ascites or four quadrant washings TAH-BSO Omental biopsy/omentectomy Systematic exploration of all peritoneal surfaces Retroperitoneal lymph nodes Ovarian Staging Not merely an academic exercise Essential to rational treatment planning Prognostic Therapeutic Repeat Staging in Apparent Stage I & II Ovarian Initial Stage No. of Patients % Upstaged Staging Laparotomy in Early Ovarian Re-exploration after initial Laparotomy in Stage I disease 46% with Grade 3 tumors upstaged 34% with Grade 2 tumors upstaged 16% with Grade 1 tumors upstaged Sites of Metastases in Apparent Stage I &II Ovarian Diaphragm 8.0% Aortic nodes 18.1% Pelvic Nodes 6.0% Omentum 8.6% Cytology 9.8% Young et al JAMA 250:3072(1983) Young et. al. JAMA 250:3072 (1983) Berek et al 1994 7
Survival Stage I/II Ovarian by Surgeon Actual Survival Gyn Oncol 83% 76% Non Oncol 53% 39% Mayer et. Al. Gynecol Oncol 47:223(1992) p<0.05 DFS p<0.03 Misstaging of Ovarian cancer General Surgery 65% deficient Gynecology 48% deficient Gyn Oncology 3% deficient McGowen et. Al. Obstet Gynecol 65:568(1985) Cytoreductive Surgery Physiologic benefits Enhanced immunologic competence Cell growth kinetics Cytoreductive Surgery Griffiths, CT Natl Inst Monogr 42:101, 1975 Residual Tumor Size 8
Radical Cytoreductive Surgery in Advanced Ovarian Multiple bowel resections Splenectomy Partial Gastrectomy Diaphragm resection Abdominal wall resection Ovarian : Surgical Treatment for Advanced Disease Significant survival advantage for women optimally cytoreduced Procedures may include: En bloc resection of uterus, ovaries and pelvic tumor Omentectomy Bowel resection Removal of diaphragmatic and peritoneal implants Splenectomy, appendectomy % 5 yr Survival Ovarian Carcinoma Prognosis by Stage Stage IIIC/IV Ovarian Variables Determining Survival P value Grade of tumor 0.01 Size of largest met NS Variables >10cm Site of largest <10cm 0.004 met Age Duration of Sx >60yrs <60yrs 0.0002 Cytoreductive outcome 0.0001 Spec. of Surgeon 0.0001 Ovarian : Importance of Surgeon 1,866 women with ovarian cancer Significant advantage for those women managed by Gynecologic Oncologist More likely to have optimal cytoreduction Reduction in death by 25% (p= 0.005) compared to Ob/Gyn and General Surgeons Junor et al, Brit J Ob/Gyn, 11/99 Eisenkop Gynecol Oncol 47:1992 National Survey of Ovarian Carcinoma I. A Patient Care Evaluation Study of the American College of Surgeons Averette et al 71: Feb 1993 12,316 patients GYO 21% OBG 45% GS 21% 12-25% had adequate surgery to permit accurate staging Significant difference in optimal debulking Significant difference in survival (p<0.004) Ovarian NCI SEER Results 10% of women received the care recommended by consensus statement on ovarian cancer 43% of women with advanced stage disease over age 65 received state-of-the-art care Trimble, E. ASCO 5, 1996 Ovarian Reasons for Inadequate Surgery Unfamiliarity with the disease, treatment, and natural history Citation of overall poor prognosis Health plans, politics? 9
Ovarian NIH Consensus Recommendations Patients with high likelihood of ovarian cancer should be given the opportunity of having surgery performed by Gynecologic Oncologist Aggressive cytoreduction at primary surgery improves long term survival Completely staged patients with Stage IA or IB, Grade 1 tumors do not require adjuvant chemotherapy Second look surgery should not be routine Taxol and a platinum compound is 1st line chemo NIH Consensus Statement 12:1-30, 1994 10