Gynecology Book


Ovarian Cancer

Aka: Ovarian Cancer, Ovarian Malignancy, Cancer of the Ovary
  1. Epidemiology
    1. Incidence: 22,000 new cases in U.S. in 2010
      1. Lifetime Risk: 1 in 70 (1.4%)
      2. Age adjusted risk: overall 12.5 cases per 100,000 women
        1. Age under 20 years: 0.7 per 100,000 women
        2. Age 20 to 50 years: 6.6 per 100,000 women
        3. Age 50 to 64 years: 26.9 per 100,000 women
        4. Age over 64 years: 48.6 to 55.6 per 100,000 women
    2. Mortality: 14,000 deaths in U.S. in 2010
      1. Accounts for 3% of cancer deaths in women
      2. Fifth most common cause of cancer death in women (lung, Breast, colon, Pancreas are more common)
  2. Risk Factors
    1. Age over 40 years (most occur over age 50 years)
      1. Exception: Germ Cell Tumors (5% of cases) are most common age 20-30 years
    2. Nulliparity
    3. Estrogen Replacement Therapy for more than 5 years
    4. Endometriosis
    5. Family History
      1. Up to 90% of Ovarian Cancer patients have no Family History of Ovarian Cancer
      2. See Hereditary Ovarian Cancer Syndromes below (e.g. BRCA, Lynch Syndrome)
      3. Accounts for up to 12% of Ovarian Cancer cases
      4. Ovarian Cancer (2 to 20 fold increased risk)
        1. One affected first degree relative: 3 fold risk
        2. Two or more relatives affected: 40% risk
        3. Site-specific Ovarian Cancer Syndrome represents another Genetic Syndrome
      5. Endometrial Cancer (Uterine Cancer)
    6. Past Medical History
      1. Endometrial Cancer
      2. Colon Cancer
      3. Breast Cancer
  3. Risk Factors: Hereditary Ovarian Cancer Syndromes
    1. Breast Cancer (Ashkenazi Jewish patients have a 10 fold increased risk of BRCA)
      1. Breast-Ovarian Cancer Syndrome
      2. BRCA1 and BRCA2 account for 10% of Ovarian Cancers
      3. BRCA1 confers 44% lifetime risk of Ovarian Cancer and typically present in the mid-40s
      4. BRCA2 confers 18% lifetime risk of Ovarian Cancer and typically presents in the mid-60s
    2. Colon Cancer (and other intestinal tumors)
      1. Hereditary Nonpolyposis Colorectal Cancer (Lynch II syndrome)
        1. Confers 10-12% lifetime Ovarian Cancer risk
        2. Associated with non-polyposis Colorectal Cancer
        3. Also associated with upper GI cancer, urinary tract cancer, Endometrial Cancer
      2. MUTYH-Associated Polyposis (Small Bowel and colon)
      3. Peutz-Jeghers Syndrome
        1. Stomach and intestinal polyps with onset as teens
    3. PTEN Hamartoma Syndrome
      1. Also associated with Thyroid and Breast Cancer
  4. Pathophysiology: Ovarian Cancer types
    1. Epithelial cell (over 85% of all overian cancers, most patients are over age 50)
      1. Subtypes
        1. Serous (40% of all Ovarian Cancers)
        2. Mucinous (25% of all Ovarian Cancers)
        3. Endometrioid (20% of all Ovarian Cancers)
    2. Stromal cell
      1. Subtypes
        1. Granulosa-theca cell
        2. Sertoli-Leydig (androblastoma)
    3. Germ cell (5% of cases, typically age 20-30 years old)
      1. Subtypes
        1. Endodermal sinus
        2. Embryonal
        3. Mature (commonly benign such as dermoid cysts)
    4. Krukenburg tumor
      1. Metastasis to ovary from Breast or Gastrointestinal Tract
  5. Evaluation: Findings that may prompt further Ovarian Cancer screening
    1. Family History suggestive of a cancer syndrome (BRCA1, BRCA2 or Lynch II) - see above
      1. Breast Cancer: Bilateral, pre-Menopause or inrences a male relative (BRCA)
      2. Ovarian Cancer in two or more first or second degree relatives (BRCA)
      3. Colon Cancer or Endometrial Cancer (ask about Lynch II cluster)
    2. Symptoms
      1. At least one of the following 6 symptoms for more than 12 days per month for less than a year
        1. Pelvic Pain
        2. Abdominal Pain
        3. Increased abdominal size
        4. Abdominal Bloating
        5. Difficulty eating
        6. Early satiety
      2. Efficacy
        1. Test Sensitivity: 56% in early Ovarian Cancer (and 79.5% in later stage disease)
        2. Test Specificity: 86% if younger than 50 years old, 90% if older than 50 years old
    3. Associated paraneoplastic syndrome and other specific presentations
      1. Subacute cerebellar degeneration
      2. Leser-Trelat Sign
        1. New onset multiple Seborrheic Keratoses
      3. Trousseau Syndrome
        1. Venous Thromboembolism (unprovoked, recurrent or migratory)
      4. Hormonal presentations related to sex cord-stromal tumors
        1. Precocious Puberty
        2. Abnormal Uterine Bleeding
        3. Virilization
    4. Exam
      1. Abdominal mass or Adnexal Mass on bimanual rectovaginal examination
        1. See Adnexal Mass for differential diagnosis
        2. Ovary >10 cm, irregularity or nodularity should prompt further evaluation
        3. Palpable ovary 3-5 years after Menopause should also undergo further evaluation
          1. Ovaries should become non-palpable after Menopause
      2. Inguinal Lymphadenopathy (although retroperitoneal involvement is more common)
      3. Sister Mary Joseph Nodule (periumbilical deep Subcutaneous Nodule associated with metastases)
    5. References
      1. Goff (2007) Cancer 109(2): 221-7 [PubMed]
      2. Roett (2009) Am Fam Physician 80(6): 609-18 [PubMed]
  6. Imaging
    1. Transvaginal Ultrasound
      1. See Pelvic Ultrasound Ovarian Mass Findings
      2. Indication: First line evaluation of Adnexal Mass
      3. Test Sensitivity: 86-94%
      4. Test Specificity: 94-96%
      5. Findings on Ultrasound suggestive of Ovarian Cancer (esp if persistent >1-3 months)
        1. Ovarian volume >20 ml premenopause, non-pregnant (>10 ml Postmenopause)
        2. Increased cyst size
        3. Increased cyst wall thickness
        4. Intracystic papillary formations
        5. Intracystic solid areas
        6. Intracystic septation (complex cyst)
    2. CT Abdomen and CT Pelvis
      1. Indication: Preoperative evaluation of Adnexal Mass; monitoring post-treatment
      2. Test Sensitivity: 90%
      3. Test Specificity: 75%
    3. MRI Abdomen and Pelvis
      1. Indication: Further characterize indeterminate Adnexal Mass
      2. Test Sensitivity: 91%
      3. Test Specificity: 88%
    4. PET Scan Abdomen and Pelvis
      1. Indication: Ovarian Cancer metastases or recurrence if implants are not detectable on CT imaging alone
      2. Test Sensitivity: 67%
      3. Test Specificity: 79%
    5. References
      1. Funt (2002) Radiol Clin North Am 40(3): 591-608 [PubMed]
  7. Labs: Diagnosis of epithelial cell tumors (>85% of Ovarian Cancer)
    1. CA-125 Radioimmunoassay
      1. Low Test Specificity and low Test Sensitivity (especially in early disease and pre-Menopause)
      2. Indications to refer to gynecologic oncology
        1. Premenopause: CA-125 >200 units/ml
        2. Post-Menopause: CA-125>35 units/ml (any elevation above normal after Menopause)
    2. Human Epididymis Protein 4 (HE4)
      1. Glycoprotein present in up to one third of ovarian tumors not expressing CA-125
      2. When performed with CA-125 improves Test Sensitivity to 83.8% and Specificity to 98.5%
  8. Labs: Diagnosis of germ cell tumors (younger patients)
    1. Germ cell tumors
      1. Beta hCG
      2. Serum Alpha-fetoprotein
    2. Sex-cord stromal tumors
      1. Inhibin A-B
    3. Other biomarkers used
      1. Neuron-sepcific enolase
      2. Lactate Dehydrogenase
  9. Labs: Other supportive labs
    1. Complete Blood Count
    2. Comprehensive metabolic panel including Serum Calcium
  10. Staging
    1. Stage I: Ovary only (25% of Ovarian Cancer diagnosis)
      1. Stage IA: One ovary involved
      2. Stage IB: Both ovaries involved
      3. Stage IC: Stage IA or IB with below:
        1. Tumor on surface of ovary or
        2. Ovarian capsule ruptured or
        3. Malignant Ascites or
        4. Peritoneal cytology positive
    2. Stage II: Pelvic Extension
      1. Stage IIA: Spread to Uterus or fallopian tubes
      2. Stage IIB: Spread to other pelvic tissues
      3. Stage IIC: Stage IIA or IIB with below
        1. Tumor on surface of ovary or
        2. Ovarian capsule ruptured or
        3. Malignant Ascites or
        4. Peritoneal cytology positive
    3. Stage III: Peritoneal implants
      1. Stage IIIA: Microscopic seeding to peritoneum
      2. Stage IIIB: Abdominal peritoneal implants <2 cm
      3. Stage IIIC: Abdominal implants >2cm or positive nodes
    4. Stage IV: Distant Metastasis
  11. Management: Surgical resection
    1. First-line tool for staging and debulking
      1. May be curative in early disease
    2. Standard resection
      1. Protocol
        1. Total abdominal Hysterectomy
        2. Bilateral salping-oopherectomy
        3. Pelvic and para-aortic Lymph Node resection
        4. Omentum resection
        5. Appendectomy (in mucinous Ovarian Cancer)
      2. Efficacy: Radical surgical resection improves survival
        1. Benefit most significant in carcinomatosis
        2. Cliby (2006) Obstet Gynecol 107:77-85 [PubMed]
    3. Fertility-sparing procedures
      1. Indications
        1. Stage I Ovarian Cancer in age 30-50 years
        2. Low malignant potential tumors
        3. Germ cell tumors
        4. Sex cord-stromal tumors
      2. Protocol
        1. Unilateral salpingo-oophorectomy
        2. Consider later total Hysterectomy and contralateral salpingoopherectomy
        3. Adjuvant Chemotherapy in these lower risk cases only if residual disease post-resection
  12. Management: Adjuvant Chemotherapy
    1. Indications
      1. Stage II-IV Ovarian Cancer (not typically for Stage I or ovary-confined disease)
    2. Typically administered every 3 weeksfor 6 cycles (70% respond)
    3. Medications: Protocols combine Platinum with Taxane
      1. Platinum Agents
        1. Cisplatin
          1. Significant Nausea and Vomiting
          2. Significant nephrotoxicity and neurotoxicity
          3. Administered over 24 hours with IV fluids
        2. Carboplatin
          1. Equivalent efficacy to Cisplatin
          2. Much less toxicity than with Cisplatin
          3. Can be administered outpatient over 3 hours
      2. Taxane Agents
        1. Paclitaxel (Taxol)
          1. Arthralgias and myalgias may be significant
          2. Risk of Peripheral Neuropathy
        2. Docetaxel
          1. Significant Neutropenia and nadir fever
          2. Less risk of adverse effects seen with Taxol
          3. May be preferred in pre-existing Neuropathy
    4. Intravenous (all 3 protocols with similar efficacy)
      1. Protocol 1: Cisplatin and Paclitaxel (Taxol)
      2. Protocol 2: Carboplatin and Paclitaxel
      3. Protocol 3: Carboplatin and Docetaxel
    5. Intraperitoneal (Regional) Chemotherapy
      1. Cisplatin is currently being used
      2. Carboplatin appears safe but efficacy not proven
    6. Current protocol recommended by NCI
      1. Cisplatin and Taxol Intraperitoneal and IV
      2. Armstrong (2006) NEJM 354:34-43 [PubMed]
    7. References
      1. Markman (2003) Hematol Oncol Clin North Am 17:957 [PubMed]
  13. Management: Ovarian Cancer Survivor
    1. Gynecologic oncology
      1. First 2 years: Visits every 2-4 months
      2. Next 3 years: Visits every 3-6 months
      3. After 5 years: Yearly (surveillance may be transitioned to primary care at this point)
    2. Exams and labs for each visit
      1. Pelvic exam
      2. Surveillance of previously elevated markers (e.g. CA-125, HE-4)
    3. Genetic Counseling
      1. As indicated if referral not already made
      2. Evaluate for risk of other hereditary cancers as well as determine risk in children
    4. Additional measures as indicated
      1. Other labs (e.g. Complete Blood Count, serum chemistry panel)
      2. Imaging (CT, MRI, PET scan, Chest XRay)
    5. References
      1. Salani (2011) Am J Obstet Gynecol 204(6): 466-78 [PubMed]
  14. Prognosis
    1. Median survival: 32 months
    2. Five year survival
      1. Overall five year survival: 40-45%
      2. Five year survival for advanced Ovarian Cancer: 17-20%
        1. Later stage Ovarian Cancer presentations account for 60% of cases
      3. Stage 1: 92% five year survival for epithelial cell (95-96% for stromal or germ cell)
      4. Stage 2: 73-78% five year survival for epithelial cell (78% for stromal or germ cell)
      5. Stage 3: 39-59% five year survival for epithelial cell (65% for stromal or germ cell)
      6. Stage 4: 17-28% five year survival for epithelial cell (35% for stromal or germ cell)
    3. Predictors of better outcome
      1. Low-grade, Stage I Epithelial cell tumor (typically in premenopausal women): 95-99% ten year survival
    4. Predictors of worse outcome
      1. Age >75 contrasted with age <45 (Hazard ratio 2.8)
      2. Residual tumor >1 cm (Hazard ratio 1.72)
      3. FIGO stage 4 versus stage 1 (Hazard ratio 11.75)
      4. Clear cell or mucinous cell tumors
    5. References
      1. Tingulstad (2003) Obstet Gynecol 101:885-91 [PubMed]
  15. Prevention
    1. Universal Ovarian Cancer screening is not recommended by USPTF, AAFP
      1. High risk patients for Genetic Syndromes (see below) should be offered Genetic Counseling
      2. Positive testing for high risk Genetic Syndromes should prompt screening protocol (see below)
    2. Factors associated with a decreased risk of Ovarian Cancer development
      1. More than one full-term pregnancy (risk decreases with each successive pregnancy)
      2. Oral Contraceptive use (extended use of 4 years reduces risk of Ovarian Cancer by 50% in BRCA patients)
      3. Surgeries that reduce uterine and ovarian Blood Flow (Hysterectomy, Tubal Ligation)
      4. Late Menarche and early Menopause
      5. Low Fat Diet
      6. Avoid postmenopausal Hormone Replacement
  16. Prevention: High Risk Patients (Hereditary Ovarian Cancer Syndromes - BRCA1, BRCA2, Lynch II)
    1. Prophylactic Oophorectomy (preferred)
      1. Oophorectomy at age 35 or when childbearing complete
      2. Estrogen Replacement after oophorectomy (not if post-menopausal)
      3. Efficacy
        1. Reduces Ovarian Cancer risk by 69-100%
        2. Peritoneal Primary papillary serous tumors may occur
    2. Surveillance (alternative for those who forestall oophorectomy)
      1. BRCA: Transvaginal Ultrasound and CA-125 every 6 months during days 1-10 of Menstrual Cycle
      2. Lynch II: Transvaginal Ultrasound annually
      3. Onset of screening
        1. Age 35 years or
        2. Start 5-10 years earlier than the earliest case in the family
      4. Efficacy
        1. Test Sensitivity: 50-71%
        2. Test Specificity: 91%
  17. References
    1. Barney (2008) Med Clin North Am 92(5): 1143-61 [PubMed]
    2. Doubeni (2016) Am Fam Physician 93(11): 937-44 [PubMed]
    3. Jevolac (2011) CA Cancer J Clin 61(3): 183-203 [PubMed]
    4. Nahhas (1997) Postgrad Med 102(3): 112-20 [PubMed]
    5. Roett (2009) Am Fam Physician 80(6): 609-18 [PubMed]
    6. Teneriello (1995) CA Cancer J Clin 45(2):71-87 [PubMed]

Malignant neoplasm of ovary (C1140680)

Definition (MEDLINEPLUS)

The ovaries are part of the female reproductive system. They produce a woman's eggs and female hormones. Each ovary is about the size and shape of an almond.

Cancer of the ovary is not common, but it causes more deaths than other female reproductive cancers. The sooner ovarian cancer is found and treated, the better your chance for recovery. But ovarian cancer is hard to detect early. Women with ovarian cancer may have no symptoms or just mild symptoms until the disease is in an advanced stage. Then it is hard to treat. Symptoms may include

  • A heavy feeling in the pelvis
  • Pain in the lower abdomen
  • Bleeding from the vagina
  • Weight gain or loss
  • Abnormal periods
  • Unexplained back pain that gets worse
  • Gas, nausea, vomiting, or loss of appetite

To diagnose ovarian cancer, doctors do one or more tests. They include a physical exam, a pelvic exam, lab tests, ultrasound, or a biopsy. Treatment is usually surgery followed by chemotherapy.

NIH: National Cancer Institute

Definition (NCI) A primary or metastatic malignant neoplasm involving the ovary. Most primary malignant ovarian neoplasms are either carcinomas (serous, mucinous, or endometrioid adenocarcinomas) or malignant germ cell tumors. Metastatic malignant neoplasms to the ovary include carcinomas, lymphomas, and melanomas.
Definition (NCI_NCI-GLOSS) Cancer that forms in tissues of the ovary (one of a pair of female reproductive glands in which the ova, or eggs, are formed). Most ovarian cancers are either ovarian epithelial carcinomas (cancer that begins in the cells on the surface of the ovary) or malignant germ cell tumors (cancer that begins in egg cells).
Concepts Neoplastic Process (T191)
MSH D010051
ICD9 183.0
ICD10 C56
SnomedCT 93934004, 154528000, 363443007
LNC LA15682-0, LA10539-7
English Cancer, Ovarian, Cancers, Ovarian, Ovarian Cancer, Ovarian Cancers, Malignant neoplasm of ovary, malignant neoplasm of ovary, cancer of ovary, ovarian cancer, malignant neoplasm of ovary (diagnosis), ovarian cancer (diagnosis), Ca ovary, Ovarian cancer NOS, Cancer of Ovary, Cancer of the Ovary, Cancers, Ovary, Ovary Cancers, OVARIAN CANCER, malignant tumor of ovary, Malign neopl ovary, ovarian ca, Cancer, Ovary, Malignant tumour of ovary (disorder), Ovaries--Cancer, Ovarian cancer, NOS, -- Ovarian Cancer, Ovarian cancer, Cancer of ovary, Malignant tumor of ovary, Malignant tumour of ovary, CA - Cancer of ovary, Ovarian Ca, Malignant tumor of ovary (disorder), ovary cancer, Malignant Neoplasm of Ovary, Malignant Neoplasm of the Ovary, Malignant Ovarian Neoplasm, Malignant Ovarian Tumor, Malignant Tumor of Ovary, Malignant Tumor of the Ovary, Ovary Cancer
Dutch ca eierstok, eierstokkanker NAO, kanker van de eierstok, maligne neoplasma van de eierstok, Maligne neoplasma van ovarium, eierstokkanker, Ovariumkanker, Tumor van het ovarium, Ovariumcarcinoom
French Cancer d'un ovaire, Carc d'un ovaire, Tumeur maligne d'un ovaire, Cancer de l'ovaire SAI, Carcinome ovarien, Cancer ovarien, Cancer de l'ovaire, Carcinome de l'ovaire, Tumeur maligne de l'ovaire, Tumeur maligne ovarienne
German Krebs des Eierstocks, boesartige Neubildung des Eierstocks, Ka des Eierstocks, Ovarialkarzinom NNB, Ovarialkarzinom, Boesartige Neubildung des Ovars, Ovarialkrebs, Krebs des Ovars, Ovarieller Krebs
Italian Carcinoma dell'ovaio, Cancro dell'ovaio NAS, Tumore maligno dell'ovaio, Cancro dell'ovaio, Cancro ovarico
Portuguese Ca do ovário, Neoplasia maligna do ovário, Cancro do ovário NE, Cancro do ovário, Câncer de Ovário, Câncer Ovariano
Spanish Neoplasia maligna de ovario, Ca de ovario, Cáncer ovárico NEOM, Cáncer de ovario, neoplasia maligna del ovario (trastorno), neoplasia maligna del ovario, tumor maligno de ovario (trastorno), tumor maligno de ovario, Cáncer ovárico, Cáncer de Ovario, Cáncer Ovárico
Japanese 卵巣癌NOS, 卵巣癌, 卵巣の悪性新生物, ランソウノアクセイシンセイブツ, ランソウガン, ランソウガンNOS
Czech Ca vaječníku, Maligní novotvar vaječníku, Maligní nádor vaječníku NOS, Maligní nádor vaječníku, Maligní nádorové onemocnění vaječníku, vaječníky - rakovina, ovarium - rakovina, rakovina ovarií, rakovina vaječníků
Korean 난소의 악성신생물
Hungarian Ovarialis rák k.m.n., Ovarialis rák, Ovarium carcinoma, Ovarium malignus neoplasia, Ovariumrák
Norwegian Kreft i eggstokkene, Eggstokkskreft, Ovarialkreft
Derived from the NIH UMLS (Unified Medical Language System)

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