KRISTEN STARBUCK, MD

ROSWELL PARK CANCER INSTITUTE

DEPARTMENT OF SURGERY

DIVISION OF GYNECOLOGIC ONCOLOGY

APRIL 19TH, 2018

GYNECOLOGIC MALIGNANCIES: Ovarian Cancer

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

Cancer statistics, 2018, Volume: 68, Issue: 1, Pages: 7-30, First published: 04 January 2018, DOI: (10.3322/caac.21442)

Trends in age-adjusted cancer incidence, 1975-2014

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 Gynecologic

Cancer Gene Mutation

Breast/Ovarian

Cancer

Ovary 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) *

Family

History of

Ovarian Cancer

Lifetime Risk

None 1.4%

1 First

Degree relative

5%

2 First

Degree relatives

7%

Hereditary Breast and Ovarian

Cancer Syndromes

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

2-3% are malignant

Most common germ cell tumor

Mature Cystic Teratoma

(Dermoid Cyst)

Most common malignant germ

cell cancer

Dysgerminoma

Sex Cord-Stromal Cancers

Granulosa Stromal Cell

Tumors

Precocious puberty

Abnormal bleeding

Thecoma

Benign, hormone-producing

Fibroma

Benign, connective

tissue

Sertoli-Leydig Tumors

Masculinization

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

Vague abdominal discomfort

Abdominal pain

Urinary frequency/

urgency

Pelvic pressure or

pain

Dyspepsia

HIGH SUSPICION

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 LDH

Endodermal Sinus Tumor AFP

Choriocarcinoma hCG

Granulosa Cell Tumor Inhibin B

Embryonal Cell Tumor hCG

Ultrasound Findings

Current Standard of Care for Advanced Ovarian Cancer

Surgical staging by gynecologic

oncologist with maximum tumor

debulking

1 cm of residual tumor

6 cycles of platinum based chemotherapy with a taxane

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 post-chemotherapy

Fertility Sparing Surgery

Stage 1 disease

Nulliparous women

Unilateral salpingo-oophorectomy, hysteroscopy and curettage, cytology, peritoneal biopsy, lymph node dissection, omentectomy

Hysterectomy and contralateral salpingo-oophorectomy 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

Walsh, SGO 2016

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