Ovarian Cancer – Causes, Symptoms, Diagnosis, Treatment and Ongoing care

Basics

There are over 21,000 new cases of ovarian cancer annually, and 14,000 women will die of their disease, making this the most lethal of gynecologic cancers.

Description

Malignancy that arises from the epithelium (85–90%), stroma, or germ cells of the ovary; also, tumors metastatic to the ovary; histologic types include:

Epithelial: Serous (tubal epithelium)Mucinous (cervical and GI mucinous epithelium)Endometrioid (endometrial epithelium)Clear cell (mesonephroid)Brenner (transitional cell epithelium)CarcinosarcomaStromal: Granulosa cell tumorTheca cell tumorSertoli–Leydig cell tumorsGynandroblastomaLipid cell tumorGerm cell: Teratoma (immature)DysgerminomaEmbryonal carcinomaGonadoblastomaEndodermal sinus tumorEmbryonal carcinomaChoriocarcinomaMetastatic disease from: BreastEndometriumLymphomaGI tract (Krukenberg tumor)Primary peritonealSystem(s) affected: GI; Reproductive; Endocrine; Metabolic

Epidemiology

Incidence

21,550 new cases/year in the US; 14,600 deaths/yearLeading cause of gynecologic cancer death in women; mortality from ovarian cancer has decreased only slightly during the last 4 decades.62% diagnosed at advanced stagePredominant age: Epithelial: Mid-50sGerm cell malignancies: Usually observed in patients <20 years of age

Prevalence

Lifetime risk for general population: 1 in 70 women develops ovarian cancer.

Risk Factors

90% of ovarian cancer is sporadic and not inherited, but family history is the most significant risk factor. 1 1st-degree relative increases risk to 5%; 2 relatives, to 7%; individuals in families with familial cancer syndromes have 20–60% risk of developing ovarian cancer.Nulligravity (or infertility), early menarche, late menopause, endometriosisEnvironmental (talc, smoking, obesity)

Genetics

Breast/ovarian cancer syndrome: Early-onset breast or ovarian cancer, autosomal dominant transmission, usually associated with BRCA-1 or BRCA-2 mutationLynch II syndrome: Autosomal dominant inheritance; increased risk for colorectal, endometrial, stomach, small bowel, breast, pancreas, and ovarian cancers; defect in mismatch repair genes

General Prevention

For epithelial cancer, frequency of ovulation appears to be important. The following factors are protective:

Use of oral contraceptives: 5 years of use decreases risk by 20%; 15 years, by 50%.MultiparityBreastfeedingTubal ligation or hysterectomy: The progestin component of oral contraceptive preparations (OCPs) may protect against ovarian cancer by regulating apoptosis of the ovarian epithelium.Recent studies have shown that no clear association exists between ovarian cancer and use of ovulation-induction agents such as clomiphene, but more long-term studies are necessary (1)[B].Nonsteroidal anti-inflammatory drug (NSAID) and acetaminophen use have been shown to reduce risk of ovarian cancer (2)[B].Women with family histories of ovarian cancer or premenopausal breast cancer should be referred for genetic counseling (3)[B].Prophylactic oophorectomy is advised for mutation carriers after child-bearing is completed or by age 35 (3)[B]. Risk of primary peritoneal carcinoma is 1% after prophylactic oophorectomy.Screening: No effective screening exists for ovarian cancer: Routine use of CA-125 and transvaginal ultrasound for screening in women of average risk is discouraged. Annual pelvic examinations are recommended, particularly in postmenopausal women. An adnexal mass in a premenarchal female or a palpable adnexa in a postmenopausal female warrants further evaluation.Women with a family history of a hereditary ovarian cancer syndrome should undergo pelvic examinations, CA-125 determination, and transvaginal ultrasonography every 6–12 months beginning at ages 25–35.

Pathophysiology

Malignant transformation of the ovarian epithelium from repeated minor trauma during ovulation may lead to this change.Most ovarian cancer (62%) presents as advanced disease. Metastatic disease may develop at the same time as the primary tumor.

Commonly Associated Conditions

AscitesPleural effusionDecrease of serum albuminBreast carcinomaBowel obstructionCarcinomatosis

Diagnosis

History

BloatingEarly satiety, anorexia, dyspepsiaSense of abdominal fullness, increased abdominal sizeAbdominopelvic pain or crampingUrinary frequency or urgency in absence of infectionFatigueDyspareuniaWeight lossSevere pain secondary to ovarian rupture or torsion most frequent in germ cell tumorsPrecocious puberty (choriocarcinoma, embryonal carcinoma)

Physical Exam

AscitesCul de sac and/or pelvic nodularityPelvic massPleural effusionOmental massCachexiaAdenopathyHirsutism in androgen-secreting germ cell tumors

Diagnostic Tests & Interpretation

Lab

Initial lab tests

CA-125 (not specific for ovarian cancer)Liver function tests (LFTs) to rule out hepatic diseaseComplete blood count (CBC)UrinalysisSerum albuminCarcinoembryonic antigen (CEA) if GI primary suspectedIf nonepithelial tumor suspected: Chorionic gonadotropin (ß-hCG [dysgerminoma, choriocarcinoma, embryonal carcinoma]), a-fetoprotein (endodermal sinus tumor, embryonal carcinoma), lactate dehydrogenase (LDH [dysgerminoma]), or inhibin (granulosa cell tumor)

Follow-Up & Special Considerations

Disorders that may alter lab results: CA-125 may be elevated from gynecologic causes (e.g., menses, pregnancy, endometriosis, peritonitis, myomas, pelvic inflammatory disease) and with ascites, pleural effusion, congestive heart failure (CHF), pancreatitis, systemic lupus erythematosus (SLE), or liver disease.

Imaging

Initial approach

Pelvic ultrasoundCXRAbdominopelvic CT scan with contrast material

Follow-Up & Special Considerations

Patients with ovarian cancer need current mammography.Barium enema or colonoscopy if a colon primary is suspected

Diagnostic Procedures/Surgery

Surgery is necessary for definitive diagnosis.Endometrial biopsy if abnormal bleeding presentParacentesis if patient not an operative candidate

Pathological Findings

Epithelial ovarian cancer commonly involves the peritoneal surfaces of the abdomen and pelvis, especially the cul de sac, paracolic gutters, and diaphragmatic surfaces.

Differential Diagnosis

GI, fallopian, or endometrial malignanciesIrritable bowel syndromeColitisHepatic failure with ascitesDiverticulitisPelvic kidneyTubo-ovarian abscess or hydrosalpinxUterine fibroidsEndometriomasPhysiologic cystsBenign or borderline neoplasms

Treatment

Medication

First Line

After surgery, most patients will require chemotherapy. Stage 1a, grade 1 and most stage 1b, grade 1 tumors do not require adjuvant therapy. Patients with clear cell carcinomas, grade 3 tumors, or tumors staged 1c or worse require adjuvant therapy. Patients should be encouraged to participate in clinical trials whenever possible.Paclitaxel (Taxol) is recommended in combination with platinum-based therapy as the 1st-line treatment of epithelial ovarian cancer (4)[A].Intraperitoneal (IP) chemotherapy in combination with IV chemotherapy improves survival in advanced ovarian cancer (5)[A]. IP chemotherapy is associated with more toxicity.Contraindications: Poor functional status, excessive toxicity, hypersensitivityPrecautions: All regimens cause bone marrow suppression. Cisplatin is associated with ototoxicity, renal toxicity, and peripheral neuropathy. Taxol can cause neutropenia and neuropathy.Antiemetic: Ondansetron (Zofran), dronabinol (Marinol), metoclopramide (Reglan), prochlorperazine (Compazine), promethazine (Phenergan)

Second Line

Liposomal doxorubicinCarboplatin/gemcitabineTopotecanTaxotereEtoposideBevacizumabCyclophosphamideTamoxifen may be used in recurrent disease when chemotherapy is not appropriate (6)[B].

Surgery/Other Procedures

Surgical exploration with staging and debulking is critical. Maximal cytoreduction of tumor burden enhances effectiveness of adjuvant therapy and is associated with longer survival.For epithelial malignancies, careful staging, tumor excision/debulking includes: Cytologic evaluation of peritoneal fluid (or washings from peritoneal lavage)Bilateral salpingo-oophorectomy with hysterectomy and tumor reductive surgeryExcision of omentumInspection and palpation of peritoneal surfacesCytologic smear of right hemidiaphragmatic surfaceBiopsy of adhesions or any suspicious areasBiopsy of paracolic recesses, pelvic sidewalls, posterior cul de sac, and bladder peritoneumPelvic and para-aortic lymph node biopsiesGerm cell cancers (less likely to be bilateral): Salpingo-oophorectomy (unilateral if only 1 ovary involved) in young patient

Ongoing Care

Prognosis

5-year survival rates for ovarian cancer based on FIGO data:

Complications

Pleural effusionPseudomyxoma peritoneiAscitesToxicity of chemotherapyBowel obstructionMalnutritionElectrolyte disturbancesFistula formation

References

1. Mahdavi A, Pejovic T, Nezhat F. Induction of ovulation and ovarian cancer: a critical review of the literature. Fertil Steril. 2006;85:819–26.

2. Collaborative Group on epidemiological Studies of Ovarian cancer: Beral V; Doll R; Hermon C, et al. Ovarian cancer and oral contraceptives: Collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls. Lancet. 2008;371:303–14.

3. Eisen A, Rebbeck TR, Wood WC, et al. Prophylactic surgery in women with a hereditary predisposition to breast and ovarian cancer. J Clin Oncol. 2000;18:1980–95.

4. McGuire WP, Hoskins WJ, Brady MF, et al. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med. 1996;334:1–6.

5. Armstrong DK, Bundy B, Wenzel L, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006;354:34–43.

6. Orlando M, Costanzo, MV, Chacon RD. Randomized trial of combination chemotherapy versus monotherapy in relapsed ovarian carcinoma: a meta-analysis of published data. J Clin Oncol. 2007;25:280s.

Codes

ICD9

183.0 Malignant neoplasm of ovary

Snomed

93934004 primary malignant neoplasm of ovary (disorder)

Clinical Pearls

Family history of ovarian cancer or early-onset breast cancer is the most significant risk factor for the development of ovarian cancer, yet the vast majority of cases remain sporadic and not inherited.The diagnosis of ovarian cancer should be suspected in women with persistent bloating, upper abdominal discomfort, or gastrointestinal symptoms of unknown etiology.