Primary prevention
There are no proven primary preventive measures for ovarian cancer, but several approaches may reduce the risk of it developing.
The use of oral contraceptives for a period of 5 years is associated with a 50% decrease in the risk of ovarian cancer, which decreases further with longer duration of use.[36][37][38][39][40]
Tubal ligation and hysterectomy are associated with a decreased risk of ovarian cancer.[52][53] However, these procedures should only be performed for valid medical reasons, not for their effect on ovarian cancer risk.
Based on data that implicate the fimbriated end of the fallopian tube as the source of serous ovarian cancer, the American College of Obstetricians and Gynecologists (ACOG) and the Society of Gynecologic Oncology have recommended that physicians discuss opportunistic salpingectomy for all patients at average risk of ovarian cancer who are undergoing hysterectomy.[54][55] However, evidence for opportunistic salpingectomy for ovarian cancer prevention is mostly derived from observational studies.[56]
Risk-reducing surgery for women at high risk
Risk-reducing salpingo-oophorectomy (RRSO) can decrease the risk of ovarian cancer in high-risk patients, such as those with: BRCA1 or BRCA2 mutations; mutations associated with Lynch syndrome; or other ovarian cancer susceptibility gene variants.[14][15][57][58][59][60][61] The decision to undergo RRSO (with or without concurrent hysterectomy) and its timing should be individualized (e.g., based on age, whether childbearing has been completed, menopausal status, comorbidities, specific gene mutation, and family history).[14][15][62]
For women with a BRCA1 mutation, guidelines recommend RRSO at ages 35 to 40 years (taking into account childbearing wishes).[15] BRCA2 variants are associated with later ovarian cancer onset, and consideration may be given to delaying RRSO until ages 40 to 45 years in these patients (unless there is a family history of early diagnosis). Hysterectomy at the time of RRSO to reduce risk of serous uterine cancer in women with a BRCA mutation may be discussed. Evidence to suggest an increased risk of serous uterine cancer among individuals with BRCA1/2 is limited.[15]
For women with a BRIP1, RAD51C, or RAD51D mutation, RRSO is recommended at ages 45 to 50 years.[15] RRSO may be considered from age 45 to 50 years in women with a PALB2 mutation. Discussions about risk-reducing surgery should start earlier if there is a family history of early-onset disease.[15]
For women with Lynch syndrome, guidelines recommend discussing risk-reducing surgery with women by their early to mid-40s.[18] Evidence supports the use of RRSO in patients with MLH1, MSH2, and EPCAM variants, but is insufficient to recommend risk-reducing surgery for those with MSH6 and PMS2 variants (which are associated with lower risk of ovarian cancer).[14]
In addition to RRSO, hysterectomy should be considered for all patients with Lynch syndrome to reduce the risk of endometrial cancer.[14]
Nonsurgical risk reduction for women at high risk
For high-risk women who decline or are unable to have RRSO, routine screening with transvaginal ultrasound and CA-125 is sometimes considered.[16][60][63] However, studies do not show a clear benefit and it is not routinely recommended.[14][15] The effectiveness of screening women at high risk for ovarian cancer using pelvic exam, CA-125 testing, and transvaginal ultrasound has not been demonstrated; early-stage disease is difficult to detect and may be missed with these approaches.[15][64]
The Risk of Ovarian Cancer Algorithm (ROCA) may have potential utility as a surveillance tool in high-risk women (e.g., with pathogenic germline BRCA1/2 variants) who defer or decline risk-reducing surgery.[65]
Surveillance of women at high risk of ovarian cancer represents an interim measure and should not be considered as an alternative to risk-reducing surgery.[66]
Consideration of combination oral contraception or a hormonal intrauterine device (IUD) is recommended as a risk-reducing measure among women with a BRCA mutation.[13][15][60] Use of a combined estrogen/progestin contraceptive or a levonorgestrel IUD (LNG-IUD) in women with BRCA1 or BRCA2 mutations has been found to reduce ovarian cancer risk to that reported for the general population.[67][68][69][70][71] Benefits and harms must be weighed and discussed with high-risk patients, including the increased risk of breast cancer associated with long-term oral contraceptive use.[62][68][71]
For women with Lynch syndrome, alternative risk-reduction strategies should be discussed if RRSO is declined or not possible.[14] This should include education about symptoms associated with ovarian cancer.
The table that follows summarizes recommendations on the primary prevention of ovarian cancer taken from National Comprehensive Cancer Network (NCCN) clinical practice guidance on genetic/familial high-risk assessment: Breast, ovarian and pancreatic.[15]
Note that an individual patient may fall into more than one group and so interventions might be additive; please review all population and subpopulation groups to assess all that apply.
Woman with one or both intact ovaries and fallopian tubes; with identified BRCA1 mutation
All
Intervention
Counseling, with recommendation of RRSO at ages 35-40 years
RRSO can decrease the risk of ovarian cancer in high-risk patients. The decision to undergo RRSO and its timing is individualized and complex, and it is recommended that the decision is made in consultation with a gynecologic oncologist, especially when the patient wishes to undergo RRSO before the age at which it is usually recommended.
The following points are typically covered as part of preoperative counseling:
Discussion of reproductive options
Extent of cancer risk/cancer worry
Degree of protection for ovarian cancer with RRSO
Risks associated with premature menopause (e.g., osteoporosis, cardiovascular disease, cognitive changes, changes to vasomotor symptoms, and sexual concerns)
Management of menopausal symptoms with hormonal replacement following surgery
Related medical or surgical history
Goal
Reduced risk of ovarian cancer
Premenopausal
Intervention
Consider nonsurgical risk-reduction agents; consider salpingectomy with delayed oophorectomy
Consider referral to a gynecologic oncologist/gynecologist in consideration of nonsurgical risk-reduction methods.
Options include consideration of:
Combination estrogen/progestin contraception (e.g., the oral contraceptive pill) for ovulation suppression
Levonorgestrel intrauterine device
Discussion with the physician and patient outlining the associated risks versus benefits is recommended. In particular, combined oral contraceptive use is associated with short-term increased risk of breast cancer but decreased long-term risk of ovarian cancer and endometrial cancer (although the long-term benefit seems to be reduced following menopausal hormone replacement therapy after bilateral salpingo-oophorectomy).
Salpingectomy (surgical removal of the fallopian tube with delayed oophorectomy) reduces the risk of ovarian cancer in the general population and is an option for premenopausal patients with hereditary cancer risk who are not yet ready for oophorectomy in the context of a clinical trial (salpingectomy is currently not proven to improve outcomes and continues to be a procedure under investigation).
Continuation of combination oral contraceptives or hormonal intrauterine device for continued ovarian cancer risk reduction while ovaries remain in place may be considered.
Goal
Reduced risk of ovarian cancer
Premenopausal; future pregnancy under consideration
Intervention
Consider fertility specialist referral
Reproductive considerations are an important part of the prevention strategy in premenopausal women.
If desired, refer to fertility specialists for discussion of age-related fertility considerations, options for in vitro fertilization, egg and embryo cryopreservation, and consideration of preimplantation genetic testing, gestational carrier, and adoption.
Goal
Inclusion of reproductive options as part of prevention strategy; attainment of the individual’s family planning objectives
Woman with one or both intact ovaries and fallopian tubes; with BRCA2 mutation
All
Intervention
Counseling, with recommendation of RRSO at ages 40-45 years
RRSO can decrease the risk of ovarian cancer in high-risk patients. It is reasonable to delay RRSO for management of ovarian cancer risk until ages 40-45 years in patients with BRCA2 variants, unless age at diagnosis in the family warrants earlier age for consideration of prophylactic surgery.
The decision to undergo RRSO and its timing is individualized and complex, and it is recommended that the decision is made in consultation with a gynecologic oncologist, especially when the patient wishes to undergo RRSO before the age at which it is typically recommended.
The following points are typically covered as part of preoperative counseling:
Discussion of reproductive options
Extent of cancer risk/cancer worry
Degree of protection for ovarian cancer with RRSO
Risks associated with premature menopause (e.g., osteoporosis, cardiovascular disease, cognitive changes, changes to vasomotor symptoms, and sexual concerns)
Management of menopausal symptoms following surgery
Hormone replacement options following surgery
Related medical or surgical history
Goal
Reduced risk of ovarian cancer
Premenopausal
Intervention
Consider nonsurgical risk-reduction agents; consider salpingectomy with delayed oophorectomy
Consider referral to a gynecologic oncologist/gynecologist in consideration of nonsurgical risk-reduction methods.
Options include consideration of:
Combination estrogen/progestin contraception (e.g., the oral contraceptive pill) for ovulation suppression
Levonorgestrel intrauterine device
Discussion with the physician and patient outlining the associated risks versus benefits is recommended.In particular, combined oral contraceptive use is associated with short-term increased risk of breast cancer but decreased long-term risk of ovarian cancer and endometrial cancer (although the long-term benefit seems to be reduced following menopausal hormone relacement therapy after bilateral salpingo-oophorectomy).
Salpingectomy (surgical removal of the fallopian tube with delayed oophorectomy) reduces the risk of ovarian cancer in the general population and is an option for premenopausal patients with hereditary cancer risk who are not yet ready for oophorectomy in the context of a clinical trial (salpingectomy is currently not proven to improve outcomes and continues to be a procedure under investigation).
Continuation of combination oral contraceptives or hormonal intrauterine device for continued ovarian cancer risk reduction while ovaries remain in place may be considered.
Goal
Reduced risk of ovarian cancer
Premenopausal; future pregnancy under consideration
Intervention
Consider fertility specialist referral
Reproductive considerations are an important part of the prevention strategy in premenopausal women.
If desired, refer to fertility specialists for discussion of age-related fertility considerations, options for in vitro fertilization, egg and embryo cryopreservation, and consideration of preimplantation genetic testing, gestational carrier, and adoption.
Goal
Inclusion of reproductive options as part of prevention strategy; attainment of the individual’s family planning objectives
Woman with one or both intact ovaries and fallopian tubes; with ATM mutation identified
All
Intervention
Individualized management based on family history
There is currently insufficient evidence to recommend RRSO in carriers of the ATM mutation; management therefore depends on family history.
Goal
Individualized management to reduce ovarian cancer risk
Premenopausal
Intervention
Consider nonsurgical risk-reduction agents
Consider referral to a gynecologic oncologist/gynecologist in consideration of nonsurgical risk-reduction methods.
Factors to consider include the age-related cancer risk of the known pathogenic variant, and family history.
Options include consideration of:
Combination estrogen/progestin contraception (e.g., the oral contraceptive pill) for ovulation suppression
Levonorgestrel intrauterine device
Discussion with the physician and patient outlining the associated risks versus benefits is recommended.
Goal
Reduced risk of ovarian cancer
Woman with one or both intact ovaries and fallopian tubes; with BRIP1, PALB2, RAD51C, or RAD51D mutation identified
All
Intervention
Counseling, with recommendation of RRSO starting at ages 45-50 years
RRSO can decrease the risk of ovarian cancer in high-risk patients. The decision to undergo RRSO and its timing is individualized and complex, and it is recommended that the decision is made in consultation with a gynecologic oncologist, especially when the patient wishes to undergo RRSO before the age at which it is typically recommended.
It is recommended that discussions about risk-reducing surgery should start earlier if there is a family history of early-onset disease.
The following points are typically covered as part of counseling:
Discussion of reproductive options
Extent of cancer risk/cancer worry
Degree of protection for ovarian cancer with RRSO
Risks associated with premature menopause (e.g., osteoporosis, cardiovascular disease, cognitive changes, changes to vasomotor symptoms, and sexual concerns)
Management of menopausal symptoms following surgery
Hormone replacement options following surgery
Related medical or surgical history
Goal
Reduced risk of ovarian cancer
Premenopausal
Intervention
Consider nonsurgical risk-reduction agents; consider salpingectomy with delayed oophorectomy
Consider referral to a gynecologic oncologist/gynecologist in consideration of nonsurgical risk-reduction methods.
Factors to consider as part of the decision-making process include the age-related cancer risk of the known pathogenic variant, and family history.
Options include consideration of:
Combination estrogen/progestin contraception (e.g., the oral contraceptive pill) for ovulation suppression
Levonorgestrel intrauterine device
Discussion with the physician and patient outlining the associated risks versus benefits is recommended.
Salpingectomy (surgical removal of the fallopian tube with delayed oophorectomy) reduces the risk of ovarian cancer in the general population and is an option for premenopausal patients with hereditary cancer risk who are not yet ready for oophorectomy in the context of a clinical trial (salpingectomy is currently not proven to improve outcomes and continues to be a procedure under investigation).
Continuation of combination oral contraceptives or hormonal intrauterine device for continued ovarian cancer risk reduction while ovaries remain in place may be considered.
Goal
Reduced risk of ovarian cancer
Premenopausal; future pregnancy under consideration
Intervention
Consider fertility specialist referral
Reproductive considerations are an important part of the prevention strategy in premenopausal women.
If desired, refer to fertility specialists for discussion of age-related fertility considerations, options for in vitro fertilization, egg and embryo cryopreservation, and consideration of preimplantation genetic testing, gestational carrier, and adoption.
Goal
Inclusion of reproductive options as part of prevention strategy; attainment of the individual’s family planning objectives
Woman with one or both intact ovaries and fallopian tubes; with Lynch syndrome genes identified
Lynch syndrome genes: MLH1, MSH2, MSH6, EPCAM
All
Intervention
Individualized management in line with published guidance on the particular gene variant
In women with Lynch syndrome genes, RRSO may reduce the incidence of ovarian cancer.
This is an individualized decision; decision and timing of RRSO depends on a number of factors including:
Whether childbearing is complete
Menopausal status
Comorbidities
Family history
Patient preference
Which Lynch syndrome gene is present; risks for ovarian cancer vary by mutated gene
Note: there is insufficient evidence to recommend RRSO in MSH6 and PMS2 P/LP variant carriers.
The decision to undergo RRSO and its timing ideally will be made in consultation with a gynecologic oncologist.
The following points are typically covered as part of presurgical counseling:
Discussion of reproductive options
Extent of cancer risk/cancer worry
Degree of protection for ovarian cancer with RRSO
Risks associated with premature menopause (e.g., osteoporosis, cardiovascular disease, cognitive changes, changes to vasomotor symptoms, and sexual concerns)
Management of menopausal symptoms following surgery
Hormone replacement options following surgery
Related medical or surgical history
Goal
Reduced risk of ovarian cancer
Premenopausal
Intervention
Consider nonsurgical risk-reduction agents; consider salpingectomy with delayed oophorectomy
Consider referral to a gynecologic oncologist/gynecologist in consideration of nonsurgical risk-reduction methods.
Factors to consider as part of the decision-making process include the age-related cancer risk of the known pathogenic variant, and family history.
Options include consideration of:
Combination estrogen/progestin contraception (e.g., the oral contraceptive pill) for ovulation suppression
Levonorgestrel intrauterine device
Discussion with the physician and patient outlining the associated risks versus benefits is recommended.
Salpingectomy (surgical removal of the fallopian tube with delayed oophorectomy) reduces the risk of ovarian cancer in the general population and is an option for premenopausal patients with hereditary cancer risk who are not yet ready for oophorectomy in the context of a clinical trial (salpingectomy is currently not proven to improve outcomes and continues to be a procedure under investigation).
Continuation of combination oral contraceptives or hormonal intrauterine device for continued ovarian cancer risk reduction while ovaries remain in place may be considered.
Goal
Reduced risk of ovarian cancer
Premenopausal; consideration of both RRSO and future pregnancy
Intervention
Fertility specialist referral
Reproductive considerations are an important part of the prevention strategy in premenopausal women.
If desired, refer to fertility specialists for discussion of age-related fertility considerations, options for in vitro fertilization, egg and embryo cryopreservation, and consideration of preimplantation genetic testing, gestational carrier, and adoption.
Goal
Inclusion of reproductive options as part of prevention strategy; attainment of the individual’s family planning objectives
Secondary prevention
Early-stage disease is difficult to detect and may be missed with pelvic examination, CA-125 testing, and ultrasound. Therefore, careful discussion between patient and physician is necessary to understand the significant limitations of these tests, even in high-risk populations.[64]
Preventive measures in women at high risk for developing ovarian cancer are discussed in the primary prevention section.
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