Ovarian cancer: identifying and managing familial and genetic risk

Commissioners and service providers should ensure that there are referral pathways to genetics services and gynaecology oncology multidisciplinary services for people at risk of having a pathogenic variant associated with ovarian cancer. Such pathways can be facilitated by providing, for example:

• clear referral criteria (see recommendation 1.3.1 in the section on assessing the risk of having a pathogenic variant)

• an online referral form (to be completed by the referring clinician)

• a family history questionnaire (to be completed by the person) that accompanies the referral form

• information and support (see the section on information and support).

Commissioners and service providers should raise awareness of which groups of people may be at risk of having a pathogenic variant associated with ovarian cancer.

Commissioners and service providers should ensure that there is training and information available for healthcare professionals on equality and inclusiveness issues that could improve access to services, for example, for people who:

• are from under-represented or underserved communities who may need more support to access services (for example, people who are physically disabled, people with neurodevelopmental conditions or a learning disability, people from Black, Asian and ethnic minority backgrounds, and people who are LGBTQ+)

• may not come forward for testing because they do not realise that they may be at risk of having a pathogenic variant associated with ovarian cancer (for example, men, trans women and non-binary people born with male reproductive organs).

Primary care should be responsible for:

• providing information and support (see the section on information and support)

• referral to genetics services and other specialist services (see recommendation 1.1.1 and recommendation 1.3.1 in the section on assessing the risk of having a pathogenic variant).

Genetics services should be responsible for:

• providing information and support (see the section on information and support)

• assessing the risk of having a pathogenic variant for people who do not have ovarian cancer

• genetic counselling and genetic testing for people who do not have ovarian cancer

• genetic counselling and genetic testing for people diagnosed with non-epithelial ovarian cancer (see recommendation 1.4.6 in the section on people with ovarian cancer)

• arranging cascade testing of relatives, if appropriate

• assessing the risk of developing ovarian cancer

• discussing potential management options

• referral (if needed) to the familial ovarian cancer multidisciplinary team and other specialist services.

The gynaecology oncology multidisciplinary team should be responsible for mainstream genetic counselling and genetic testing for people with invasive epithelial ovarian cancer.

The familial ovarian cancer multidisciplinary team should be responsible for:

• clinical care pathways and management protocols

• the lifelong care of people at risk of familial ovarian cancer (those with a pathogenic variant or those above a risk threshold; see the section on criteria for genetic counselling and genetic testing)

• providing information and support (see the section on information and support)

• assessing the risk of developing ovarian cancer

• discussing potential management options (for example, risk-reducing surgery)

• carrying out surveillance and reviews

• liaising with other services and healthcare professionals, including primary care and specialist services (see recommendation 1.1.9)

• contributing to local and network audits

• facilitating access to clinical trials.

The familial ovarian cancer multidisciplinary team should have a designated lead clinician, and include healthcare professionals with expertise in areas including:

• clinical genetics

• gynaecology

• gynaecological oncology.

The familial ovarian cancer multidisciplinary team should have established relationships with, and agreed referral pathways to, other specialist services such as:

• psychological services

• menopause services

• fertility services

• breast cancer risk management services

• ovarian cancer services

• colorectal cancer services.

Healthcare professionals in all settings (primary care, genetics services and specialist multidisciplinary services) should provide ongoing information and support in line with:

• table 1 on information and support about familial ovarian cancer in all settings

• NICE's guideline on patient experience in adult NHS services – particularly the section on knowing the patient as an individual

• NICE's guideline on people's experience in adult social care services – particularly the section on overarching principles related to enabling people to make decisions (for example, in relation to communication)

• NICE's guideline on shared decision making – particularly the section on putting shared decision making into practice.

Healthcare professionals should ensure that information and support:

• supports shared decision making

• is balanced and accurate

• is available on an ongoing basis

• is available when needed

• is relevant to the person's circumstances

• is tailored to the person's needs, for example, it is in an accessible format or available in a different language.

Provide opportunities for people to review decisions, and share any additional information on how they can access services for further discussions, for example, at:

• re-referral to specialist services

• patient-initiated follow‑up appointments directly with specialist services

• self-referral to genetics services.

At each appointment:

• ask the person about their emotional health

• ask about any psychological or emotional issues that could affect decision making, such as anxiety

• provide information and support (see table 1 on information and support about familial ovarian cancer in all settings)

• discuss referral to genetic counselling or psychological services, as appropriate.

Raise awareness that men, trans women and non-binary people born with male reproductive organs can have a genetic risk of having a pathogenic variant associated with ovarian cancer and other cancers.

Ensure that services are easy to access (for example, by offering online appointments) and welcoming for everyone, particularly for people who may have additional support needs (also see recommendation 1.1.3).

Healthcare professionals in genetics services should provide ongoing information and support in line with:

• table 2 on information and support about risk assessment and genetic testing in genetics services and

• table 1 on information and support about familial ovarian cancer in all settings.

In genetics services, a healthcare professional with skills and experience in information provision and shared decision making specifically related to genetics and cancer risk should offer genetic counselling to people who meet the referral criteria for genetic testing. See the sections on assessing the risk of having a pathogenic variant and criteria for genetic counselling and genetic testing.

Take into account the following factors when deciding whether to offer face-to-face or remote (for example, video call, telephone) genetic counselling:

• the person's preference

• the decision that needs to be made (for example, genetic testing or risk-reducing surgery)

• accessibility needs (for example, geographic location, digital access, language or communication impairment, participation of family members in other locations)

• the need for an interpreter.

Consider giving information in a group session before an individual genetic counselling session.

Consider using a patient decision aid (for example, an app) alongside genetic counselling to support shared decision making. See the recommendations on patient decision aids in the NICE guideline on shared decision making.

Healthcare professionals in specialist services (genetics services, gynaecology oncology multidisciplinary teams and familial ovarian cancer multidisciplinary teams) should provide ongoing information and support in line with:

• table 3 on information and support in specialist services if a person has a pathogenic variant or a strong family history of ovarian cancer and

• table 1 on information and support about familial ovarian cancer in all settings.

Genetics services should offer genetic counselling and genetic testing to anyone who:

• has not had ovarian cancer and

• has a raised probability of having a pathogenic variant (see table 4 on genetic testing criteria) based on a verified family history and

• has a relative who has had a confirmed diagnosis of breast cancer or ovarian cancer but genetic testing of the relative (or the tissue) is not possible or clinically appropriate (for example, consent is declined).

If a person has not had ovarian cancer, genetics services should offer genetic counselling and genetic testing if they are a first-degree relative of a person with a known pathogenic variant (cascade testing).

If a person has not had ovarian cancer, genetics services should offer genetic counselling and genetic testing if:

• they are a second-degree or more distant blood relative of a person with a known pathogenic variant and

• testing of an intervening blood relative is impossible or not clinically appropriate (for example, consent is declined).

If a person has a personal or family history of breast cancer, also see the NICE guideline on familial breast cancer, in particular the sections on the clinical significance of a family history of breast cancer, and referral to a specialist genetic clinic.

Recognise and raise awareness that people from the following populations (with at least 1 grandparent from the respective population), have a higher risk of having a founder pathogenic variant associated with familial ovarian cancer, so should be offered referral for genetic counselling and genetic testing for this variant, even if the person has no family or personal history of cancer:

• Ashkenazi Jewish

• Sephardi Jewish

• Greenlander.
  
  Also see the NHS Jewish BRCA Testing Programme, which offers BRCA testing to people with Jewish ancestry.

Offer pre-test counselling and germline testing to anyone diagnosed with:

• invasive epithelial ovarian cancer

• ovarian Sertoli–Leydig cell tumour

• small cell carcinoma of the ovary hypercalcaemic type

• ovarian sex cord tumour with annular tubules

• embryonal rhabdomyosarcoma of the ovary

• ovarian gynandroblastoma.

Do not offer aspirin for the sole purpose of reducing ovarian cancer risk.

For recommendations on the use of aspirin for people with Lynch syndrome, see the section on reduction in risk of colorectal cancer in people with Lynch syndrome in the NICE guideline on colorectal cancer.

Only consider the combined oral contraceptive pill to reduce the risk of ovarian cancer:

• if the reduction in the risk of developing ovarian cancer outweighs the increased risk of developing breast cancer and

• after taking into account the timing of any risk-reducing surgery (mastectomy or salpingo-oophorectomy; see the section on risk-reducing surgery).
  
  In March 2024, this was an off‑label use of combined oral contraceptives. See NICE's information on prescribing medicines.

Discuss the reduced risk of developing ovarian cancer and the increased risk of developing breast cancer when offering a combined oral contraceptive.

Only offer risk-reducing surgery to people who have:

• completed their family or are not planning to conceive naturally (that is, they would only conceive using assisted reproduction) and

• a total lifetime risk of ovarian cancer of 5% or over because they have:

  • a pathogenic variant associated with familial ovarian cancer or

  • a strong family history of ovarian cancer.

When discussing risk-reducing surgery, provide information and support in line with:

• table 3 on information and support in specialist services if a person has a pathogenic variant or a strong family history of ovarian cancer and

• table 1 on information and support about familial ovarian cancer in all settings.

When discussing risk-reducing surgery, take into account psychological factors (such as anxiety) that could influence decision making. Discuss psychological support services available and, if needed, refer the person for psychological support before surgery.

When discussing risk-reducing bilateral salpingo-oophorectomy surgery with people who are premenopausal:

• offer specialist menopause counselling before and after surgery and

• provide information and support to aid shared decision making (also see the section on information and support, in particular table 3 on information and support in specialist services if a person has a pathogenic variant or a strong family history of ovarian cancer, and the section on hormone replacement therapy after risk-reducing surgery).

Refer people who have bi-allelic pathogenic variants in mismatch repair genes (for example, homozygous PMS2), to a specialist tertiary team for discussions about risk-reducing surgery.

Offer risk-reducing surgery that is appropriate for the person's age, specific pathogenic variant and family history (including age of onset of any confirmed ovarian cancers in the family), after discussing the person's individual circumstances with the familial ovarian cancer multidisciplinary team. See table 5 on timing and types of risk-reducing surgery for people with a pathogenic variant that increases the risk of ovarian cancer.

Consider risk-reducing total hysterectomy alone to prevent endometrial cancer for people (no earlier than 45 years) who have:

• a heterozygous PMS2 pathogenic variant and

• no family history of ovarian cancer.

If a person with a heterozygous PMS2 pathogenic variant has been offered total hysterectomy to prevent endometrial cancer, consider additional bilateral salpingo-oophorectomy depending on verified family history of ovarian cancer, age and menopausal status.

Consider risk-reducing surgery in people younger than the ages in table 5 on timing and types of risk-reducing surgery after carrying out an individualised risk assessment (including an assessment of menopausal symptoms) and providing information and support to aid shared decision making (also see the section on information and support).

Only offer risk-reducing bilateral salpingectomy with delayed oophorectomy as part of a clinical trial.

Do not carry out risk-reducing total hysterectomy in people with pathogenic variants other than MLH1, MSH2, MSH6 and PMS2, unless a personalised risk assessment shows a high risk of endometrial cancer that would necessitate hysterectomy or there is another gynaecological indication for hysterectomy.

Before carrying out risk-reducing bilateral salpingo-oophorectomy, perform a transvaginal ultrasound and a serum CA125 test to minimise the risk of missing asymptomatic ovarian cancer.

Before carrying out a risk-reducing hysterectomy, perform an endometrial biopsy to minimise the risk of missing asymptomatic endometrial cancer.

If asymptomatic cancer is identified by preoperative investigation or postoperative histopathological or cytopathological analysis, refer the person to the gynaecology oncology multidisciplinary team (see the section on the gynaecology oncology multidisciplinary team).

Carry out risk-reducing minimal access surgery, unless a laparotomy is more clinically appropriate.

Take peritoneal washings during risk-reducing surgery for cytological examination to test for the presence of malignant cells.

If any suspicious lesions are found outside the organs being removed, take a biopsy if it is feasible and safe to do.

If a person is at risk of developing ovarian cancer and chooses to delay or not have risk-reducing surgery, discuss their reasons and explain that:

• they have an increased risk of developing ovarian cancer and that the only way to reduce their risk is to have risk-reducing surgery

• delaying risk-reducing surgery should only be seen as a short-term option

• regular surveillance does not reduce their risk of developing ovarian cancer

• although regular surveillance means that ovarian cancer may be detected earlier, they should not view surveillance as an alternative to risk-reducing surgery (because there is little evidence on whether this leads to improved outcomes and saves lives)

• surveillance will involve them having a blood test every 4 months to check their level of the protein CA125 (cancer antigen 125), with an algorithm to analyse results, and a review at least once a year to discuss the recommendation of having risk-reducing surgery

• there is a possibility of getting a false-positive or false-negative test result.

The familial ovarian cancer multidisciplinary team (see the section on familial ovarian cancer multidisciplinary teams) should only consider surveillance for people in the following groups who are at risk of developing ovarian cancer but who choose to delay or not have risk-reducing surgery (see also table 5 on timing and types of risk-reducing surgery):

• over 35 and have a BRCA1 pathogenic variant or

• over 40 and have a BRCA2 pathogenic variant or

• over 45 and have RAD51C, RAD51D, BRIP1 and PALB2 pathogenic variants.

If carrying out surveillance (see recommendation 1.8.19), the familial ovarian cancer multidisciplinary team should:

• carry out serial 4‑monthly CA125 longitudinal testing using an algorithm with demonstrated accuracy (for example, the Risk of Ovarian Cancer Algorithm [ROCA] Test)

• coordinate, audit and interpret CA125 testing using a call and recall system

• have a review appointment with the person at least once a year to discuss the recommendation of having risk-reducing surgery (see the section on risk-reducing surgery).