By Molly A. Brewer, DVM, MD, MS
Professor and Chair, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Carole and Ray Neag Comprehensive Cancer Center, University of Connecticut Health Center, Farmington
Dr. Brewer reports that she receives grant/research support from the National Cancer Institute.
SYNOPSIS: This article discusses the role of salpingectomy for the prevention of ovarian and fallopian tube cancer.
SOURCE: Falconer H, et al. Ovarian cancer risk after salpingectomy: A nationwide population-based study. J Natl Cancer Inst 2015;107: pii: dju410. doi: 10.1093/jnci/dju410.
The incidence of ovarian cancer is low in the general population, with a 1.5-1.7% lifetime risk of ovarian or fallopian tube cancer. Despite the low incidence, presentation of ovarian cancer is often in late stages and is associated with the highest mortality rate of any of the gynecologic cancers. As a result of this poor prognosis, significant efforts have been directed toward early detection. Unfortunately, studies evaluating screening tools in the general population (i.e., CA125, transvaginal ultrasound)1 have failed to improve survival. In the last 20 years, the paradigm has shifted with the discovery of deleterious BRCA1 and BRCA2 gene mutations, which are linked to a significantly increased risk of both breast and ovarian cancer compared to the general population. Women with a BRCA1 gene mutation have a 60-85% lifetime risk for breast cancer and a 40-60% lifetime risk for ovarian cancer. Women with a BRCA2 gene mutation have a 60-85% and 17-27% risk for breast and ovarian cancer, respectively.
Women at high risk for ovarian cancer likely represent a different population of women. Specifically, women with a deleterious BRCA1 or BRCA2 gene mutation represent a population requiring surveillance and fertility planning that is thoughtful and deliberate. Once childbearing is complete, the primary form of cancer prevention in this population is ultimately prophylactic surgery. Women with a BRCA mutation who undergo risk-reducing salpingo-oophorectomy (RRSO) have a 4-12% risk that they will have an associated occult malignancy of the adnexa at the time of prophylactic surgery.2-8 As physicians have become more aware of the risk of an occult malignancy, better techniques for pathologic evaluation of the ovary and the fallopian tube have been recommended.5,6 Studies have found that up to 75% of these occult cancers arose from the fallopian tube. As these findings became publicized, there was a move to perform salpingectomy on women to prevent fallopian tube cancer. In addition, some physicians have recommended salpingectomy in lieu of RRSO in young women with a BRCA mutation. In 2011, Greene et al addressed the role of salpingectomy and the deleterious effects of ovary removal in young women. The researchers concluded that salpingectomy without oophorectomy in this population should be experimental only due to the unproven clinical utility of this approach.9
In January 2015, the first clinical trial was published addressing the role of salpingectomy in the prevention of ovarian cancer.10 This population-based cohort study used data from a nationwide health registry supervised by the Swedish Board of Health. The researchers compared women who underwent salpingectomy (unilateral or bilateral) with women who had hysterectomy and bilateral salpingo-oophorectomy (BSO), hysterectomy alone, sterilization alone (tubal ligation), salpingectomy (unilateral or bilateral), or no treatment. They found that there was a reduction in the risk of ovarian cancer in all women who had a procedure compared to the untreated population. Hysterectomy had a hazard ratio (HR) of 0.79 (95% confidence interval [CI], 0.7-0.88), hysterectomy and BSO had an HR of 0.06 (CI, 0.03-0.12), salpingectomy had an HR of 0.65 (CI, 0.52-0.81), and sterilization had an HR of 0.72 (CI, 0.64-0.81). Sterilization, salpingectomy, and hysterectomy all had approximately the same reduction in risk (0.79 vs 0.65 vs 0.72), suggesting that disruption of the connection to the ovary may have been the common denominator. Interestingly, removing both tubes was associated with a more substantial reduction in risk, with an HR of 0.39 (CI, 0.18-0.87), but only after 10 years. This CI is substantially wider than the rest, suggesting there were small numbers and heterogeneity within this group. Hysterectomy and BSO had substantially more protection with an HR of 0.06 (CI, 0.03-0.12). Criticisms of the study were significant because the authors did not include the impact of oral contraceptive pills (OCPs), which would be a substantial confounder, as OCPs have been found to universally decrease the risk of ovarian cancer, which increases with an increased duration of use. This risk reduction may be > 50% when used ≥ 10 years.11 In addition, the numbers of cancers were small and the numbers of women undergoing bilateral salpingectomy were extremely small, which may limit the applicability of these data. That being said, these are rare cancers unless a woman harbors a BRCA mutation, where the risk of ovarian cancer may be as high as 54%.12-14
COMMENTARY
Should all women undergo salpingectomy? Currently, the data do not confirm the clinical utility of this procedure; taking OCPs for more than 5 years may reduce the risk as much and spare a woman an invasive procedure. Havrilesky et al conducted a meta-analysis that showed that OCPs taken for more than 120 months reduced the odds of developing ovarian cancer by almost 60%, with an odds ratio (OR) approaching 0.43 (CI, 0.37-0.51). This is almost equivalent to bilateral salpingectomy after 10 years.11 The time since last OCP use influences risk reduction with 0-10 years having an OR of 0.41 (CI, 0.34-0.5) and 10-20 years having an OR of 0.65 (CI, 0.56-0.74).10 Thus, OCP use is almost equivalent to bilateral salpingectomy and is based on 10,031 cases and 21,025 controls, a much larger number than represented in the Swedish study salpingectomy study. In addition, this is a reversible form of contraception and avoids a surgical procedure. Each risk-reducing gesture has its own set of risks and benefits, and like most clinical situations, needs to be weighed for each individual patient.
So how should we counsel women? Tailoring the recommendation to the patient seems to be the most prudent approach. Salpingectomy provides permanent contraception with the same surgical risk and a lower failure rate than a tubal ligation, which has been associated with a reduction in the risk of ovarian cancer (HR, 0.76; 95% CI, 0.64-0.90).15 However, if a patient is at increased risk for ovarian cancer, the role of salpingectomy is less clear. In women with a BRCA mutation, anywhere from 50-75% of the cancers are thought to arise from the fallopian tube, based on data at the time of RRSO. However, there are no data supporting the use of salpingectomy in these high-risk women, and extrapolating the very limited data on salpingectomy in the general population to high-risk women may jeopardize their health: Performing salpingectomy in lieu of RRSO may, in fact, decrease their probability of survival. In particular, women with a BRCA1 mutation have a 4% incidence of ovarian cancer between the ages of 35 and 40 years, suggesting that RRSO should be performed in these women around the age of 35 years or once they have completed their childbearing. Extrapolating data from women with a BRCA mutation to the general population is not appropriate since the populations are different. Furthermore, performing unnecessary RRSO in women at low risk for ovarian cancer has been associated with adverse outcomes such as an increased risk of coronary artery disease (HR, 1.34; < 45 years of age), increased risk of stroke (HR, 1.21; < 45 years of age), and all-cause death (HR, 1.18; < 45 years of age).16 Women with a strong family history of breast and ovarian cancer who are BRCA negative on traditional Myriad testing are now being found to have mutations in genes not previously associated with an increased risk of ovarian cancer, such as TP53, BARD1, CHEK2, RAD51, and PALB2, so appropriate referral for genetic counseling and testing should be done based on a comprehensive family history prior to making a decision about salpingectomy vs RRSO.
In conclusion, tailoring the recommendations to perform salpingectomy to the individual patient is the safest, most appropriate approach. Performing universal salpingectomy for prevention of ovarian and fallopian tube cancer without another indication is not supported at this time.
REFERENCES
- Menon U, et al. Ovarian cancer screening — current status, future directions. Gynecol Oncol 2014;132:490-495.
- Stratton JF, et al. Comparison of prophylactic oophorectomy specimens from carriers and noncarriers of a BRCA1 or BRCA2 gene mutation. United Kingdom Coordinating Committee on Cancer Research (UKCCCR) Familial Ovarian Cancer Study Group. J Natl Cancer Inst 1999;91:626-628.
- Lu KH, et al. Occult ovarian tumors in women with BRCA1 or BRCA2 mutations undergoing prophylactic oophorectomy. J Clin Oncol 2000;18:2728-2732.
- Leeper K, et al. Pathologic findings in prophylactic oophorectomy specimens in high-risk women. Gynecol Oncol 2002;87:52-56.
- Powell CB, et al. Risk-reducing salpingo-oophorectomy (RRSO) in BRCA mutation carriers: Experience with a consecutive series of 111 patients using a standardized surgical-pathological protocol. Int J Gynecol Cancer 2011;21:846-851.
- Powell CB, et al. Risk-reducing salpingo-oophorectomy in BRCA mutation carriers: Role of serial sectioning in the detection of occult malignancy. J Clin Oncol 2005;23:127-132.
- Callahan MJ, et al. Primary fallopian tube malignancies in BRCA-positive women undergoing surgery for ovarian cancer risk reduction. J Clin Oncol 2007;25:3985-3990.
- Finch A, et al. Clinical and pathologic findings of prophylactic salpingo-oophorectomies in 159 BRCA1 and BRCA2 carriers. Gynecol Oncol 2006;100:58-64.
- Greene M, et al. Does bilateral salpingectomy with ovarian retention warrant consideration as a temporary bridge to risk-reducing bilateral oophorectomy in BRCA1/2 mutation carriers? Am J Obstet Gynecol 2011;204:19e1-19.
- Falconer H, et al. Ovarian cancer risk after salpingectomy: A nationwide population-based study. J Natl Cancer Inst 2015;107: pii: dju410. doi: 10.1093/jnci/dju410.
- Havrilesky LJ, et al. Oral contraceptive pills as primary prevention for ovarian cancer: A systematic review and meta-analysis. Obstet Gynecol 2013;122:139-147.
- Brose MS, et al. Cancer risk estimates for BCRA1 mutation carriers identified in a risk evaluation program. J Natl Cancer Inst 2002;94:1365-1372.
- Ford D, et al. Risks of cancer in BRCA1-mutation carriers. Lancet 1994;343:692-695.
- Easton D. Cancer risks in BRCA2 mutation carriers: the breast cancer linkage consortium. J Natl Cancer Inst 1999;91:1310-1316.
- Rice MS, et al. Tubal ligation, hysterectomy, unilateral oophorectomy, and risk of ovarian cancer in the Nurses’ Health Studies. Fertil Steril 2014;102:192-198.e3.
- Parker WH, et al. Ovarian conservation at the time of hysterectomy and long-term health outcomes in the nurses’ health study. Obstet Gynecol 2009;113:1027-1037.
This article discusses the role of salpingectomy for the prevention of ovarian and fallopian tube cancer.
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