Ovarian cancer risk-reducing surgery

For women, trans men, and non-binary people born with female reproductive organs with a total lifetime risk of ovarian cancer of ≥5% because of a pathogenic variant or a strong family history that increases the risk of ovarian cancer, NICE recommends offering risk-reducing surgery (bilateral salpingo-oophorectomy and peritoneal cytology).

Timing and types of risk-reducing surgery for people with a pathogenic variant that increases the risk of ovarian cancer

MLH1, MSH2, or MSH6 pathogenic variants have also been included as they cause Lynch syndrome, which is associated with an increased risk of endometrial and ovarian cancer

* Total hysterectomy, including the cervix, to ensure the removal of all at-risk tissue.

NICE states:

• 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 cancer
      • a person has a strong family history of ovarian cancer if they have 1 or more first-degree relatives (for example, a grandmother, mother, sister or daughter) on the same side of their family (the mother's or father's side of the family) with ovarian cancer
• 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

The NICE committee noted (1):

• decisions related to risk-reducing surgery for ovarian cancer should take into account the NICE guideline on familial breast cancer because some of the genes associated with ovarian cancer would also increase the risk of breast cancer, so considerations around risk-reducing mastectomy should be made in line with the NICE familial breast cancer guideline
• with respect to the evidence that bilateral salpingo-oophorectomy improves overall survival
  • noted that most of the evidence came from studies with carriers of the BRCA1 or BRCA2 variants
  • based on the evidence, they recommended bilateral salpingo-oophorectomy for people at increased risk of ovarian cancer with BRCA1 and BRCA2, and also RAD51C, RAD51D, BRIP1 or PALB2, which are also associated with an increased risk of ovarian cancer
  • MLH1, MSH2 or MSH6 pathogenic variants are associated with Lynch syndrome, which is associated with an increased risk of endometrial as well as ovarian cancer
    • noted that there was no evidence identified related to different types of surgery within this specific group, but the committee decided that total hysterectomy as well as bilateral salpingo-oophorectomy should be recommended to prevent both of these types of cancers
    • noted that PMS2 is also associated with Lynch syndrome (and is therefore on the associated gene panel)
      • PMS2 increases the risk of endometrial cancer alone rather than endometrial as well as ovarian cancer. They therefore did not add it to the table of risk-reducing surgery for people at risk of ovarian cancer
      • committee made separate recommendations related to the PMS2 pathogenic variant because of its link to Lynch syndrome
        • people with this pathogenic variant have an increased risk of endometrial cancer alone, but could have an increased risk of ovarian cancer if there is also a family history of ovarian cancer
          • therefore considered it to be safe to only recommend total hysterectomy for people with a heterogenous PMS2 pathogenic variant unless there is also a family history of ovarian cancer when additional bilateral salpingo-oophorectomy could be considered
• committee noted that MLH1, MSH2, MSH6 and PMS2 increase the risk of endometrial cancer, and therefore a hysterectomy is indicated only for carriers of these pathogenic variants

Reference:

1. NICE (March 2024). Ovarian cancer: identifying and managing familial and genetic risk