GYNECOLOGIC MALIGNANCIES: Ovarian Cancer KRISTEN STARBUCK, MD ROSWELL PARK CANCER INSTITUTE DEPARTMENT OF SURGERY DIVISION OF GYNECOLOGIC ONCOLOGY APRIL 19 TH, 2018
Objectives Basic Cancer Statistics Discuss subtypes, surgical treatment, medical treatment, preventative, and novel treatment of: Ovarian cancer (Tomorrow): Endometrial cancer Cervical Cancer Vulvar/Vaginal Cancer
US Mortality (2016) Age-adjusted mortality rates Heart disease: 611,105 Cancer: 584,881 Chronic lower respiratory diseases: 149,205 Accidents (unintentional injuries): 130,557 Stroke (cerebrovascular diseases): 128,978 Alzheimer's disease: 84,767 Diabetes: 75,578 Influenza and Pneumonia: 56,979 Nephritis, nephrotic syndrome, and nephrosis: 47,112 Intentional self-harm (suicide): 41,149 Source CDC 2018.
US Mortality (2016) Heart disease: 635,260 23.1% Cancer: 598,038 21.8% Accidents (unintentional injuries): 161,374 5.9% Chronic lower respiratory diseases: 154,596 Stroke (cerebrovascular diseases): 142,142 Alzheimer's disease: 116,103 Diabetes: 80,058 Influenza and Pneumonia: 51,537 Nephritis, nephrotic syndrome, and nephrosis: 50,046 Intentional self-harm (suicide): 44,965 Source CDC 2018.
US Cancer Incidence and Mortality (2015)
Projected new cancer cases and deaths, 2018
Trends in age-adjusted cancer incidence, 1975-2014 Cancer statistics, 2018, Volume: 68, Issue: 1, Pages: 7-30, First published: 04 January 2018, DOI: (10.3322/caac.21442)
Ovarian Cancer
Incidence/Prevalence Cancer.gov / SEER.gov
Stage at diagnosis and survival
Risk Factors for Ovarian Cancer Increased Risk Decreased Risk Age Oral Contraceptive Pills Family History of Ovarian Cancer Pregnancy Infertility Tubal Ligation Low Parity Breastfeeding
Oral Contraceptive Pills *
Hereditary Breast and Ovarian Cancer Syndromes
Hereditary Breast and Ovarian Cancer Syndromes Syndrome Breast/Ovarian Cancer Gynecologic Cancer Ovary Gene Mutation BRCA 1(30-40%risk OC) BRCA 2 (15-25% risk OC) HNPCC (Lynch Syndrome) Uterine, Ovary MSH2, MLH1, MSH6 (40-60% risk uterine, 6-20% risk OC) *
Hereditary Breast and Ovarian Cancer Syndromes Family History of Ovarian Cancer Lifetime Risk None 1.4% 1 First Degree relative 2 First Degree relatives 5% 7%
Ovarian Cancer Preventative Measures for BRCA 1 & 2 Patients Birth Control Pills Reduce risk by 45-60% Tubal Ligation (BTL) Reduces risk by ~60% BTL & Birth Control Pills Reduce risk by 72% Bilateral Salpingo-oophorectomy Reduces risk by 80% Reduces risk of breast cancer by 50%
Ovarian Cancers
Histologic Distribution
Germ Cell Cancers Derived from germ cell of ovary Most common germ cell tumor Most common malignant germ cell cancer 2-3% are malignant Mature Cystic Teratoma (Dermoid Cyst) Dysgerminoma
Sex Cord-Stromal Cancers Granulosa Stromal Cell Tumors Thecoma Fibroma Sertoli-Leydig Tumors Precocious puberty Benign, hormoneproducing Benign, connective tissue Masculinization Abnormal bleeding Hirsutism
Histologic subtypes of epithelial ovarian carcinoma and associated mutations/molecular aberrations. *, CHK2, BARD1, BRIP1, PALB2, RAD50, RAD51C, ATM, ATR, EMSY, Fanconi anemia genes. Susana Banerjee, and Stanley B. Kaye Clin Cancer Res 2013;19:961-968 2013 by American Association for Cancer Research
Symptoms of Ovarian Cancer Bloating HIGH SUSPICION Vague abdominal discomfort Dyspepsia Abdominal pain Pelvic pressure or pain Urinary frequency/ urgency
Diagnosis of Ovarian Cancer Routine pelvic exams in asymptomatic women detect only 1 in 10,000 ovarian cancers
Tumor Markers Histology Tumor Marker Epithelial Ovarian Cancer CA 125 Dysgerminoma Endodermal Sinus Tumor Choriocarcinoma Granulosa Cell Tumor Embryonal Cell Tumor LDH AFP hcg Inhibin B hcg
Ultrasound Findings
Current Standard of Care for Advanced Ovarian Cancer Surgical staging by gynecologic oncologist with maximum tumor debulking 6 cycles of platinum based chemotherapy with a taxane 1 cm of residual tumor
Treatment-Staging Surgery Peritoneal washings: diaphragm, right and left abdomen, and pelvis Inspection and palpation of all peritoneal surfaces Biopsy or smear from right hemidiaphragm Biopsy all suspicious lesions Infracolic omentectomy Biopsy or resection of any adhesions Random biopsy of peritoneum of bladder reflection, cul-de-sac, both paracolic gutters, and pelvic side walls Pelvic and para-aortic lymph node dissection TAH, BSO
Surgical bulk resection is of little value unless all gross tumor is excised
Neoadjuvant Chemotherapy Chemotherapy given before surgery Allows patients who have unresectable disease at initial surgery to have a higher chance of being maximally cytoreduced Useful for patients who are medically compromised Ongoing research into molecular changes pre- and postchemotherapy
Fertility Sparing Surgery Stage 1 disease Nulliparous women Unilateral salpingo-oophorectomy, hysteroscopy and curettage, cytology, peritoneal biopsy, lymph node dissection, omentectomy Hysterectomy and contralateral salpingooophorectomy when child bearing is complete
Common Sites of Spread
Stages 1- one or both ovaries II-other pelvic organs III-outside the pelvis/peritoneal mets IV-distant mets excluding peritoneal mets
Treatment-Chemotherapy
Intraperitoneal Chemotherapy Higher doses of chemotherapy Longer half life Works best on minimal disease
Platinum-sensitivity and response to subsequent treatment
Goals for Improving Patient Survival Enrollment in clinical trials Aggressive surgical management by well trained specialists Maximal tumor cytoreduction Adjuvant chemotherapy with platinum and taxane based regimens
Current Standard of Care for Early Stage Ovarian Cancer
Ovarian Cancer: Future Research Directions Effective screening- currently no effective screening Early detection- biomarker development Prevention Overcoming chemo-resistance Targeted therapies Parp inhibition Folate receptor alpha-targeting Ab Mucin-targeting Ab Immunotherapy* Checkpoint inhibition Cancer testis antigens Immunoprofiling TIL therapy/act Genetically modified TCR and CAR-T cell therapies
NY-ESO-1 Predicts an aggressive phenotype of ovarian cancer Szender et al., 2017