Ovarian Cancer Guidelines

Updated: Apr 03, 2017
  • Author: Andrew E Green, MD; Chief Editor: from Memorial Sloan-Kettering - Yukio Sonoda, MD  more...
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Guidelines

Guidelines Summary

Guidelines Contributor: Jori S Carter, MD, MS, Assistant Professor, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Virginia Commonwealth University School of Medicine

Screening

The U.S. Preventive Services Task Force (USPSTF) has concluded that annual screening of asymptomatic women with transvaginal ultrasonography and testing for a serum tumor marker, cancer antigen (CA)–125, does not reduce ovarian cancer deaths, but can lead to major surgical interventions in women who do not have cancer. With the harms of screening outweighing the benefits, USPSTF recommends against routine screening. [3]

The consensus among major medical organizations is in agreement with the USPSTF that screening for ovarian cancer in the general population is not recommended. However, the American College of Obstetricians and Gynecologists (ACOG) and the Society of Gynecologic Oncologists (SGO) recommend that women at high risk be offered an evaluation includes transvaginal ultrasonography, CA-125 testing, and a thorough pelvic examination. [101]

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Risk Assessment and Genetic Counseling

The following organizations have issued guidelines for genetic risk assessment of women with BRCA1 and BRCA2 mutations, Lynch syndrome (hereditary nonpolyposis colon cancer), or a family history of ovarian cancer:

  • U.S. Preventive Services Task Force (USPSTF)
  • National Comprehensive Cancer Network (NCCN)
  • American Society of Clinical Oncology (ASCO)
  • European Society for Medical Oncology (ESMO)
  • American College of Obstetricians and Gynecologists (ACOG)
  • Society of Gynecologic Oncologists (SGO)

U.S. Preventive Services Task Force

In 2014, the USPSTF issued updated guidelines on risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women. The recommendation is that primary care providers screen women who have a family history of breast, ovarian, tubal, or peritoneal cancer using one of several available brief familial risk tools, including the following [102] :

  • Ontario Family Health Assessment Tool
  • Manchester Scoring System
  • Referral Screening Tool
  • Pedigree Assessment Tool
  • FHS-7

Women with a positive screening result should receive genetic counseling, with further BRCA testing if warranted. Women without a family history associated with an increased risk for mutations should not receive routine genetic counseling or BRCA testing.

National Comprehensive Cancer Network

The NCCN provides specific criteria for genetic counseling and testing of BRCA, as well as additional genetic mutations associated with ovarian cancer risk: CDH1STK11/LKB1, and Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC]) genes. Separate criteria for genetic evaluation is given for individuals affected with breast or ovarian cancer and unaffected individuals with a family history suggestive of genetic risk. [103]

The criteria for affected individuals include having at least one of the following risk factors:

  • Known genetic mutation within the family or from a population at increased risk
  • Breast cancer before age 50
  • Triple negative (estrogen receptor, progesterone receptor, HER2-) breast cancer
  • Two primary breast cancer tumors
  • Breast cancer and a close relative with breast cancer before age 50, or ovarian cancer at any age, or two or more close relatives with breast cancer or pancreatic cancer at any age
  • A family member with a combination of breast cancer and either pancreatic cancer, prostate cancer, sarcoma, adrenocortical carcinoma, brain tumors, endometrial cancer, leukemia/lymphoma, thyroid cancer, hamartomatous polyps of the GI tract, or diffuse gastric cancer
  • Ovarian cancer

The criteria for unaffected individuals include a family history of at least one of the following:

  • Known genetic mutation within the family or from a population at increased risk
  • One individual with two or more primary breast cancer tumors
  • Two or more individuals on the same side of the family with breast cancer
  • Ovarian cancer
  • First- or second-degree relative with breast cancer before age 45
  • A family member with a combination of breast cancer and either pancreatic cancer, prostate cancer, sarcoma, adrenocortical carcinoma, brain tumors, endometrial cancer, leukemia/lymphoma, thyroid cancer, hamartomatous polyps of the GI tract, or diffuse gastric cancer
  • Male breast cancer

Women who meet the assessment criteria should receive genetic counseling, with further BRCA testing if warranted. Multi-gene testing may be considered in some women.

American Society of Clinical Oncology

In 2010, ASCO released general guidelines for genetic testing for cancer susceptibility. Genetic testing is recommended when the patient has a  personal or family history suggestive of genetic cancer susceptibility, the test can be adequately interpreted, and the results will aid in diagnosis or medical management of the patient or family member. ASCO also recommends genetic testing only when pretest and posttest counseling are included. [104]

European Society of Medical Oncology

Guidelines from ESMO, released in 2011, note that testing criteria differ between countries based on the population prevalence of the mutation and include not only specific criteria very similar to that of NCCN, but also more general criteria such as a having a 10-20% probability of finding a mutation based on predictive models, or the assumption of a potential benefit in the medical or surgical management of the individual or close family members. [105]

Overall, ESMO recommends that all patients referred for BRCA testing first complete informed consent and genetic counseling and that those who are mutation carriers be encouraged to advise close family members to obtain genetic counseling. [105]

American College of Obstetricians and Gynecologists

Guidelines issued by ACOG in 2009 recommend genetic risk assessment for women who have more than a 20% to 25% risk for an inherited predisposition to breast and ovarian cancer. [106]

Society of Gynecologic Oncologists

In 2014, the Society of Gynecologic Oncologists updated its clinical practice statement on genetic testing for ovarian cancer to recommend that all women diagnosed with ovarian cancer receive genetic counseling and be offered genetic testing regardless of family history. [107]

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Surgical Intervention for Ovarian Cancer Prevention

The NCCN recommends bilateral salpingo-oophorectomy (RRSO) for risk reduction in women with BRCA1 or BRCA2 mutations, ideally at the age of 35-40 years and upon completion of childbearing or at an individualized age based on earliest age of ovarian cancer diagnosed in the family. [103] Both the USPSTF and ACOG also support offering salpingo-oophorectomy for risk reduction to women with BRCA1 or BRCA2 mutations. [102, 106] ESMO guidelines concur and suggest that the surgery take place after age 35 and childbearing is completed. [105]

The NCCN guidelines also note that women considering RRSO should be made aware of the increased risk of osteoporosis and cardiovascular disease associated with premature menopause, as well as the potential effects of possible cognitive changes, accelerated bone loss, and vasomotor symptoms on quality of life. [103]

SGO guidelines are in agreement that women who have BRCA mutations should be offered RRSO, after completion of childbearing, as the best strategy for reducing their risk of developing ovarian cancer. The guidelines further recommend that for those women who choose not to undergo RRSO because of the health risks and impact on quality of life associated with premature menopause, physicians may offer the option of salpingectomy after childbearing is completed, followed by oophorectomy in the future. However, women who delay oophorectomy will remain at risk for developing ovarian cancer. Additionally, they will not benefit from the 50% reduction in breast cancer provided through premenopausal oophorectomy. [108]

The SGO advises that pathologic processing of RRSO specimens from high-risk women should include micro-sectioning of the ovaries and tubes, with special attention to the fimbriae. [108]

For women at average risk of ovarian cancer, risk-reducing salpingectomy should also be considered at the time of abdominal or pelvic surgery or hysterectomy or in lieu of tubal ligation. The pathologic specimen processing in low risk-women should include representative sections of the tube, any suspicious lesions, and entire sectioning of the fimbriae. [108]

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Diagnostic Evaluation

The American College of Obstetricians and Gynecologists has established referral guidelines for a patient with a newly diagnosed pelvic mass. Women who meet the criteria below would benefit from preoperative consultation with a gynecologic oncologist. [101]

For premenopausal women, referral criteria are as follows:

  • CA-125 level greater than 200 units/mL
  • Ascites
  • Evidence of abdominal or distant metastasis (on examination or imaging study)
  • Family history of breast or ovarian cancer in a first-degree relative

For menopausal women, referral criteria are as follows:

  • Elevated CA-125 levels (any degree of elevation)
  • Ascites
  • Nodular or fixed pelvic mass
  • Evidence of abdominal or distant metastasis (on examination or imaging study)
  • Family history of breast or ovarian cancer in a first-degree relative

The Naitonal Comprehensive Cancer Network (NCCN) guidelines make a category 1 recommendation that in all patients undergoing surgical evaluation for ovarian cancer, the procedure should be performed by an experienced gynecologic oncologist. [37]

Guidelines from the SGO and American Society of Clinical Oncology (ASCO) contain a strong recommendation, similar to that of the NCCN, that all women with suspected stage IIIC or IV invasive epithelial ovarian cancer be evaluated by a gynecologic oncologist to determine whether they are candidates for primary cytoreductive surgery. [36]

Staging

Two major staging systems are commonly used in ovarian cancer, as follows:

  • The International Federation of Gynecology and Obstetrics (FIGO) system, developed in collaboration with the World Health Organization (WHO) and revised in 2014. [109]
  • The TNM system, developed by the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC); the 7 th edition was published in 2010, and an 8 th edition is expected in 2016. [110]
  • The TNM and FIGO staging systems for ovarian and primary peritoneal cancer are also used for malignant germ cell tumors, malignant sex cord-stromal tumors, and carcinosarcoma (malignant mixed Müllerian tumors). [109, 110]

For details on these systems, see Ovarian Cancer Staging

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Primary Treatment

According to the National Comprehensive Cancer Network (NCCN) guidelines, surgery is the primary treatment for ovarian cancer, followed in most patients by systemic chemotherapy. The aim of surgery is to confirm the diagnosis, define the extent of disease, and resect all visible tumor. [37]

Additional recommendations are as follows: [37]

  • Initial surgery is comprehensive staging laparotomy, including total abdominal hysterectomy and bilateral salpingo-oophorectomy performed by a gynecologic oncologist
  • For stage 1A or 1C and/or low-risk ovarian tumors, unilateral salpingo-oophorectomy may be acceptable in younger women who wish to retain fertility; comprehensive staging is still required
  • Cytoreductive surgery for stage II, III or IV; residual disease of less than 1 cm is evidence of optimal cytoreduction, although the greatest possible effort should be made to remove all obvious disease
  • Patients with stage III or IV disease who are not fit for surgery should receive neoadjuvant chemotherapy
  • Neoadjuvant chemotherapy is not recommended when surgery is possible, and upfront debulking surgery remains the treatment of choice
  • Only a small percentage of women with epithelial ovarian cancer can be treated with surgery alone; however, for patients with stage IA or IB, observation is recommended because survival is greater than 90% for this group with surgical treatment alone
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Chemotherapy

In 2016, the Society of Gynecologic Oncology (SGO) and American Society of Clinical Oncology (ASCO) released guidelines for neoadjuvant chemotherapy (NACT) in newly diagnosed patients with advanced ovarian cancer. The SGO/ASCO guidelines include the following recommendations [36] :

  • NACT should be given to women with a high risk profile or a low likelihood of achieving cytoreduction to <1 cm
  • Primary cytoreductive surgery is recommended over NACT for women with high likelihood to achieve cytoreduction <1 cm with good and acceptable morbidity.
  • For women who are fit for primary cytoreductive surgery, with potentially resectable disease, either NACT or primary cytoreductive surgery may be offered.
  • Histologic confirmation (core biopsy preferred) of an invasive ovarian, fallopian tube, or peritoneal cancer should be obtained before NACT is initiated.
  • Platinum/taxane doublet is preferred for NACT; alternate regimens, containing a platinum agent, may be selected based on individual patient factors.
  • Interval cytoreductive surgery should be performed after ≤4 cycles of NACT with a response to chemotherapy or stable disease. 
  • In women with progressive disease on NACT, surgery is indicated only for palliation (eg, relief of a bowel obstruction). Other treatment options include alternative chemotherapy regimens, clinical trials, and/or initiation of end-of-life care.

National Comprehensive Cancer Network (NCCN) guidelines recommend that patients wishing to preserve fertility be referred to a fertility specialist prior to initiation of therapy. [37] For primary chemotherapy, NCCN recommendations are as follows [37] :

  • High-risk stage IA, IB, or IC epithelial ovarian cancer – Three to six cycles of intravenous (IV) taxane/carboplatin adjuvant chemotherapy
  • Stage II-IV disease – Intraperitoneal chemotherapy, in patients with <1 cm optimally debulked stage II and III disease; or IV taxane/carboplatin for six to eight cycles
  • Stage II-IV disease, in patients who achieve complete remission with primary treatment – Observation alone; participation in a clinical trial; or postremission paclitaxel (category 3) or pazopanib (category 2B)

For a first recurrence, the NCCN prefers combination platinum-based chemotherapy. Agents for platinum-resistant disease include the following:

  • Docetaxel
  • Etoposide
  • Gemcitabine
  • Liposomal doxorubicin +/- bevacizumab
  • Paclitaxel +/- bevacizumab
  • Topotecan +/- bevacizumab

Agents for targeted therapy include bevacizumab and olaparib. Hormonal therapy agents may include aromatase inhibitors, leuprolide, megestrol, or tamoxifen.

For details on chemotherapy regimens, see Ovarian Cancer Treatment Protocols

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Surveillance

The Society of Gynecologic Oncologists 2011 guidelines for post-treatment surveillance include the following [111] :

  • Physical examination including pelvic exam and lymph node assessment every 3 months for the first 2 years, every 4-6 months for the third year, then every six months for the next 2 years, and annually thereafter
  • CA-125 is optional
  • CT and/or PET scan only if recurrence is suspected

The National Comprehensive Cancer Network recommendations are similar and include the following [37] :

  • Physical examination including pelvic exam every 2-4 months for the first 2 years, 3-6 months for the next 2 years, and annually after year 5
  • CA-125 or other tumor marker assays at every visit if initially elevated
  • Genetic risk evaluation should be conducted, if not previously done
  • CT, MRI, PET-CT, or PET as clinically indicated
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