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JOGC

No. 344-Opportunistic Salpingectomy and Other Methods of Risk Reduction for Ovarian/Fallopian Tube/Peritoneal Cancer in the General Population

      Abstract

      Objective

      This guideline reviews the potential benefits of opportunistic salpingectomy to prevent the development of high grade serous cancers (HGSC) of the ovary/fallopian tube/peritoneum based on current evidence supporting the fallopian tube origin of disease.

      Intended Users

      Gynaecologists, obstetricians, family doctors, registered nurses, nurse practitioners, residents, and health care providers.

      Target Population

      Adult women (18 and older):
      • Who have completed childbearing, and
      • Who will undergo a gynaecologic procedure such as hysterectomy or permanent sterilization with the intention of leaving the ovaries in situ.

      Options

      Women considering hysterectomy who wish to retain their ovaries in situ have traditionally also retained their fallopian tubes. In addition, women undergoing permanent surgical sterilization have usually undergone tubal ligation using various methods rather than undergoing surgical removal of the entire fallopian tube.

      Evidence

      For the sections “Evidence Supporting the Hypothesis That HGSC Originates in the Fallopian Tube” and “Current Literature on the Effects and Safety of Opportunistic Salpingectomy,” relevant studies were searched in PubMed, Medline, and the Cochrane Systematic Reviews using the following terms, either alone or in combination, with the search limited to English language materials: “high grade serous cancers ovary,” “fallopian tube,” “peritoneum,” “opportunistic salpingectomy,” “epithelial ovarian cancers,” “origin,” “tubal carcinoma in situ,” “BRCA mutation,” “prophylactic salpingectomy,” “inflammation,” “clear cell,” and “endometrioid.” The initial search was performed in March 2015 with a final literature search in March 2016. Relevant evidence was selected for inclusion in the following order: meta-analyses, systematic reviews, guidelines, randomized controlled trials, prospective cohort studies, observational studies, non-systematic reviews, case series, and reports. The total number of studies identified was 458, and 56 studies were included in this review. For the section “Other Factors Influencing the Risk of Developing “Ovarian” Cancers” a general Medline search was carried out using the terms “ovarian neoplasm” and “prevention.” The search included papers published from December 2005 to March 2016. Meta-analyses were preferentially selected except where no such review was found. Additional searches for each subheading were also conducted (e.g., “ovarian neoplasm” and “tubal ligation.”) Additional significant articles were identified through cross-referencing the identified reviews.
      For the search for “ovarian neoplasm” and “prevention,” 10 meta-analyses were identified. For the search for “ovarian neoplasm” and “tubal ligation,” an additional 4 meta-analyses were identified.

      Validation Methods

      The content and recommendations were drafted and agreed on by the principal authors. The Executive and Board of the Society of Gynecologic Oncology of Canada reviewed the content and submitted comments for consideration, and the Board of the SOGC approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development and Evaluation methodology framework (Table 1). The interpretation of strong and weak recommendations is described in Table 2. The summary of findings is available on request.

      Benefits, Harms, and/or Costs

      The addition of opportunistic salpingectomy to a planned hysterectomy or permanent sterilization did not increase rates of hospital readmission (OR 0.91, 95% CI 0.75 to 1.10 and OR 0.8, 95% CI 0.56 to 1.21, respectively) or blood transfusions (OR 0.86, 95% CI 0.67 to 1.10 and OR 0.75, 95% CI 0.32 to 1.73, respectively) but did increase the overall operating time (by 16 minutes and 10 minutes, respectively) in a retrospective review of 43 931 women. The risk of repeat surgery for tubal pathology among women with retained fallopian tubes after hysterectomy was at least doubled (OR 2.13, 95% CI 1.88 to 2.42 in a population-based study of 170 000 women). If general gynaecologists were to consider removal of fallopian tubes at the time of every hysterectomy and sterilization procedure with referral of all patients with HGSC for hereditary cancer counselling and genetic testing, experts project a potential reduction in the rate of HGSC by 40% over the next 20 years.

      Guideline Update

      Evidence will be reviewed 5 years after publication to decide whether all or part of the guideline should be updated. However, if important new evidence is published prior to the 5-year cycle, the review process may be accelerated for a more rapid update of some recommendations.

      Sponsors

      This guideline was developed with resources funded by the Society of Gynecologic Oncology of Canada and SOGC.

      Summary Statements

      • 1.
        High-grade serous cancers of the ovary/fallopian tube/primary peritoneum account for approximately 70% of all epithelial cancers and differ from other epithelial cancers in their presentation, most prevalent stage, response to treatments, overall prognosis, and recurrence rates (High).
      • 2.
        Fallopian tube cancers, previously believed to be quite rare, are high-grade serous cancers approximately 90% of the time and have identified precursor lesions (serous tubal intraepithelial carcinomas), whereas precursor lesions have not been identified on the epithelial surface of the ovary (High).
      • 3.
        The recent change to the International Federation of Gynecology and Obstetrics staging system for high-grade serous cancers in 2014 included ovary, fallopian tube, and primary peritoneum together as primary sites of disease, reflecting the difficulty in distinguishing the location in which the cancer developed (High).
      • 4.
        Prophylactic bilateral salpingo-oophorectomy can reduce the risk of high-grade serous cancers by 80% to 90% for breast cancer mutation carriers (High).
      • 5.
        In women with breast cancer mutations, 5% to 6% of fallopian tubes from prophylactic salpingo-oophorectomies have serous tubal intraepithelial carcinomas present (High).
      • 6.
        Serous tubal intraepithelial carcinomas are found most commonly at the fimbriated end of the fallopian tube and have p53 mutation changes identical to associated cancers (High).
      • 7.
        Clear cell and endometrioid carcinomas are now believed to originate from endometriotic lesions deposited within the pelvis and around the ovary (High).
      • 8.
        Oral contraceptive pill use effectively reduces the lifetime risk of developing an “ovarian” cancer by 50% when taken for more than 10 years (High).
      • 9.
        Tubal ligation reduces the risk of endometrioid cancer by 52% and clear cell cancer by 48%, presumably by blocking retrograde menstruation and preventing endometriotic deposits within the pelvis. However, tubal ligation reduces the risk of developing high-grade serous cancers by only 19%, supporting the theory that these cancers arise within the distal end of the remaining fallopian tube (Moderate).
      • 10.
        The strategy with greatest potential for risk reduction is bilateral salpingo-oophorectomy, which reduced the mortality rate from “ovarian” cancer in the Nurses' Health Study by 94%; however, the overall risk of death from any cause following bilateral salpingo-oophorectomy increased by 12%, reflecting the protective effect of estrogen in preventing cardiovascular disease before age 50 (High).
      • 11.
        The effect of diet and obesity on “ovarian” cancer risk is currently unclear and requires further research (Low).
      • 12.
        The role of metformin in the primary prevention of “ovarian” cancer needs further research for clarification (Low).
      • 13.
        There is insufficient evidence to link the use of talc-containing products with “ovarian” cancer (Moderate).
      • 14.
        Acetylsalicylic acid has been shown to reduce the risk of “ovarian” cancer, but the effect of non-acetylsalicylic acid, non-steroidal anti-inflammatory drugs and acetaminophen is unclear (Moderate).
      • 15.
        There has been no effective screening protocol to date that can decrease mortality from “ovarian” cancer in the general population (Moderate).
      • 16.
        There is no established link between the use of “ovulation stimulating drugs” and “ovarian” cancer (Moderate).
      • 17.
        Treating endometriosis may reduce the risk of “ovarian” cancer (Low).
      • 18.
        Performing opportunistic salpingectomy at the time of hysterectomy for benign gynaecologic disorders does not increase complication rates, length of hospital stay, or overall recovery time but does lead to a minor increase in surgical time (Moderate).
      • 19.
        Retaining the fallopian tubes at the time of hysterectomy increases the risk of subsequent reoperation for tubal pathology (Moderate).
      • 20.
        Population-based studies are required to evaluate whether opportunistic salpingectomy can reduce the incidence of high-grade serous cancers (Moderate).

      Recommendations

      • 1.
        The use of an oral contraceptive pill reduces the risk of users developing high-grade serous cancers and should be discussed when counselling women on contraceptive use (Strong, High).
      • 2.
        When considering permanent contraception, tubal ligation is shown to have the additional benefit of reducing the risk of developing high-grade serous cancers. However, the fact that the complete removal of the fallopian tube may provide additional benefit should be discussed (Strong, High).
      • 3.
        Removal of the ovaries in premenopausal women may increase the risk of cardiovascular disease and is not recommended without clinical indication (Strong, High).
      • 4.
        Population-based screening should not be encouraged as a method of “ovarian” cancer risk reduction (Strong, High).
      • 5.
        In considering hysterectomy with the ovaries remaining in situ, the fact that the removal of easily accessible fallopian tubes may reduce the risk of developing high-grade serous cancers without additional procedural risk, and is recommended, should be discussed (Strong, Moderate).
      • 6.
        Prospective population-based surgical databases should be kept to monitor the effect of opportunistic salpingectomy on overall morbidity and mortality and especially the rates of high-grade serous cancers (Strong, Moderate).

      Key Words

      Abbreviations:

      ASA (acetylsalicylic acid), BRCA (breast cancer), BTL (bilateral tubal ligation), CI (confidence interval), CS (Caesarean section), EOC (epithelial ovarian cancers), FIGO (International Federation of Gynecology and Obstetrics), HGSC (high-grade serous cancers), HR (hazard ratio), IVF (in vitro fertilization), OCP (oral contraceptive pill), OR (odds ratio), RR (relative risk), SEE-FIM (sectioning and extensively examining the fimbria), STIC (serous tubal intraepithelial carcinomas)
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