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Two experts take sides on the clinical merits of performing bilateral salpingectomy alone versus removing the tubes in BRCA mutation carriers.
By Denise R. Nebgen, MD, PhD
Dr. Nebgen is an Associate Professor in the Department of Gynecologic Oncology and Reproductive Medicine, and a member of the Clinical Cancer Genetics Program at The University of Texas MD Anderson Cancer Center, Houston.
She has no conflict of interest to disclose with respect to the content of this article.
Ovarian cancer is deadly, with approximately 25,000 cases diagnosed and 12,500 deaths per year in the United States.1 Despite huge international efforts, there are no effective methods of screening for the disease. The lifetime risk of ovarian cancer in women in the general population is 1.5%, compared with a 10% to 46% risk of developing the disease by age 70 among those with BRCA mutation.2
Owing to their elevated risk, many women with BRCA mutations undergo risk-reducing bilateral salpingo-oophorectomy (BSO) at approximately age 40, which reduces their risk of ovarian cancer by 80% or more,3,4 but results in early menopause. Thorough pathologic analysis of specimens from these women has revealed a 4%–17% incidence of occult malignancy, with most of the lesions in the distal portion of the Fallopian tube or fimbria.5,6 Multiple studies have demonstrated a sequence of events known as the tubal carcinogenic pathway that lead to the development of serous tubal intraepithelial carcinomas and invasive ovarian carcinoma in BRCA mutation carriers.5 The Fallopian tube origin of BRCA-associated ovarian cancer, along with the challenges associated with premature menopause following risk-reducing BSO, have led to an interest in performing prophylactic bilateral salpingectomy (BS) with delayed oophorectomy in women with BRCA mutations. Current clinical data demonstrating the efficacy of BS are sparse, but empiric surgical procedures and clinical trials, including one in BRCA women at the authors’ facility, are under way.
The next question that arises is whether routine removal of the Fallopian tubes during surgical procedures is justified in women in the general population who have completed childbearing. We know that bilateral tubal ligation (BTL) reduces ovarian cancer risk by 50% not only in women with BRCA mutations, but also in the general population of women. What we don’t know is the extent to which salpingectomy would further decrease the risk of ovarian cancer. Recent findings show that prophylactic salpingectomy performed in combination with hysterectomy or in place of currently used sterilization procedures does not increase the risk of complications.
The results of a retrospective study that compared BS with BTL alone in 43,931 women in British Columbia were recently published.7 The study’s aim was to assess the uptake and perioperative safety of BS as an ovarian cancer risk reduction strategy in women at low risk of ovarian cancer after the introduction of this concept throughout the province as an educational initiative. The study found that the rate of performance of BS instead of routine BTL increased from 0.5% to 35% over the 4-year period between 2008 and 2011. The operating room time for BS was a mean of 10.2 minutes longer than for BTL alone. The patients in the BS group showed no significant increase in hospital readmissions, blood transfusion, or length of stay compared with the corresponding group, including procedures performed in the peripartum setting.
Concerns about an increased risk of complications from BS in the postpartum setting due to increased tissue vascularity were addressed in an abstract presented at the American College of Obstetricians and Gynecologists Annual Clinical Meeting in May 2014. Hsieh et al. found no increase in complications in 59 cases of postpartum distal salpingectomy compared with 61 historical controls.8 Vaginal delivery followed by distal salpingectomy resulted in a mean of 5 minutes more operating time and 10 mL more estimated blood loss per case than vaginal delivery followed by modified Pomeroy tubal ligation.
Cesarean delivery with distal salpingectomy resulted in a mean of 17 minutes more operating time but 171 mL less estimated blood loss than cesarean delivery with BTL. Thus, both this study and the Canadian study indicated minimal additional risk with the performance of BS. The risk of regret after permanent sterilization with BS is also a concern; however, in vitro fertilization offers patients a viable option if childbearing is desired.
More data are needed to determine if sporadic ovarian cancer also originates in the distal Fallopian tube. The ovarian cancer risk reduction efficacy data for BS will take time to produce but look promising. I support BS at the time of BTL as an ovarian cancer risk reduction measure because of the low morbidity of the procedure and the potential significant benefit. Bilateral salpingectomy does not increase the overall time of the surgical procedure or decrease its safety and, with appropriate education, could be implemented into routine practice. Approximately 600,000 BTLs are performed in the United States annually.9
Performing BS rather than BTL for women desiring permanent sterilization can theoretically decrease the incidence of ovarian cancer by more than 50% in this large population of women with little to no increased surgical risk.
1. Quirk JT, Natarajan N, Mettlin CJ. Age-specific ovarian cancer incidence rate patterns in the United States. Gynecol Oncol. 2005;99:248–250.
2. Lancaster JM, Powell CB, Kauff ND, et al. Society of Gynecologic Oncologists Education Committee statement on risk assessment for inherited gynecologic cancer predispositions. Gynecol Oncol. 2007;107:159–162.
3. Finch A, Beiner M, Lubinski J, et al. Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 Mutation. JAMA. 2006;296:185–192.
4. Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst. 2009;101:80–87.
5. Chene G, Rahimi K, Mes-Masson AM, Provencher D. Surgical implications of the potential new tubal pathway for ovarian carcinogenesis. J Minim Invasive Gynecol. 2013;20:153–159.
6. Yates MS, Meyer LA, Deavers MT, et al. Microscopic and early-stage ovarian cancers in BRCA1/2 mutation carriers: building a model for early BRCA-associated tumorigenesis. Cancer Prev Res (Phila). 2011;4:463–470.
7. McAlpine JN, Hanley GE, Woo MM, et al. Opportunistic salpingectomy: uptake, risks, and complications of a regional initiative for ovarian cancer prevention. Am J Obstet Gynecol. 2014;210:471 e1- e11.
8. Hsieh GL, Antony K, Masand R, Anderson M. A prospective feasibility study of postpartum distal salpingectomy. Obstet Gynecol. 2014;123 Suppl 1:92S.
9. Westhoff C, Davis A. Tubal sterilization: focus on the U.S. experience. Fertil Steril. 2000;73:913–922.
No. The potential for harm must be balanced with the potential for benefit.
By Kevin J. Doody, MD
Dr. Doody is Clinical Professor, University of Texas Southwestern Medical Center at Dallas, and Director, Center for Assisted Reproduction, Bedford, Texas.
He has no conflict of interest to disclose with respect to the content of this article.
Any push to perform salpingectomy for sterilization must be data-driven, not theoretical. We must have good reason to consider a more radical surgical procedure than is necessary to carry out the immediate task at hand. Tubal interruption (by clip, ring, cautery, or mid-segmental excision) is, without debate, less radical than salpingectomy. The advantages of the simpler procedure are many and generally include: 1) shorter operating time; 2) fewer and smaller incisions; 3) lower risk of complications; and 4) reversibility.
The proposed rationale for salpingectomy as a better method of sterilization than conventional tubal interruption techniques is based on 2 premises: a lower failure rate and a reduction in the incidence of ovarian cancer.
The failure rate for sterilization procedures done by tubal interruption techniques has been well studied. The conclusion of a recent large systematic review is that sterilization failure is rare with any technique, and even less likely if an experienced practitioner has performed the procedure.1 Although the failure rate is certainly lower with salpingectomy, the risk/benefit is not clear.
There are many gaps in our knowledge of the risk/benefits of salpingectomy for sterilization as compared with tubal interruption. What we do know is that approximately half of pelvic serous epithelial cancers classified as ovarian have concomitant serous tubal intraepithelial carcinoma with apparent common clonal origin.2 This relationship appears to be nearly universal for BRCA-positive patients, but it is less consistent for those without BRCA mutations.
These recent observations regarding the possible tubal origins of some cases of epithelial ovarian cancer have led many to infer that removal of Fallopian tubes might be employed for sterilization as a reasonable strategy to further reduce the risk and thus decrease long-term mortality. Unfortunately, this strategy is unproven. Level 1 data to support this practice are glaringly absent.
Case control and cohort analyses suggest that bilateral tubal ligation alone appears to reduce the likelihood of ovarian cancer by approximately 25%.3 The reduction appears to be greatest for non-serous tumors, but the trend is seen for serous tumors as well. Surprisingly, the reduction in ovarian cancer risk appears to be greater for tubal ligation than for hysterectomy. Unilateral oophorectomy also appears to reduce the risk of ovarian cancer by 30% (independent of tubal ligation or hysterectomy).
It might make sense to consider an unproven but theoretical benefit in patients known to be at high risk of developing ovarian cancer (although salpingectomy without oophorectomy in BRCA-positive patients remains controversial). We should, however, exercise greater caution before making widespread changes to our clinical practice for patients at low risk of ovarian malignancy. If we choose to use theory rather than hard data to make large-scale changes in clinical management, why should we stop at bilateral salpingectomy (BS)? Why not do a unilateral oophorectomy as well? There are currently no proposals recommending prophylactic unilateral oophorectomy in addition to BS in women who desire sterilization to reduce the risk of ovarian cancer (despite theoretical benefits) and that is for good reason. The potential for harm is real and this must be considered when balancing the potential for benefit. Salpingectomy is more extreme than Fallopian tube interruption and may have unintended consequences. In some cases, anatomy or surgical technique might result in impairment of ovarian blood supply. This could lead to earlier menopause with associated health risks.
Other unintended consequences may arise from the handling of discussions with patients regarding contraception options. The suggestion that salpingectomy reduces ovarian cancer risk might steer patients away from long-acting reversible contraceptives and other less-permanent options. It is a non-disputed fact that even well-counseled patients often change their mind following “permanent sterilization.” Remorse or regret is indeed the most common “complication” of sterilization, far outpacing sterilization failure and ovarian cancer. In a large study of 11,232 women, the cumulative probability of regret was 20% among women age 30 or younger at sterilization and 6% among women older than 30.4 Couples will have unexpected life-changing events. Women will divorce and remarry. Children die from mishap or natural cause.
Despite the caution that sterilization is permanent and irreversible, a properly performed tubal interruption is generally easily reversed with a minimally invasive approach. Although in vitro fertilization (IVF) can be an option for some women and time to conception can be reduced, it is generally more expensive, less successful, and associated with an increased risk of multiple gestation when compared with sterilization reversal surgery. In our experience, when patients are fully informed regarding both treatment options, few patients choose IVF.
The best argument against routine salpingectomy for sterilization is not the lack of reversibility. Medicine has a long history demonstrating that the road to good intentions is frequently paved with unfavorable unintended consequences. A recently published Markov Monte Carlo simulation suggests that routine salpingectomy for sterilization will, on average, increase a woman’s life span by 1 week.5 That may be overly optimistic as the mathematical model is based on unproven assumptions and does not take into account unpredicted consequences or potential advances in medical technology. Randomized controlled trials to address long-term morbidity and mortality are not feasible.
We should, however, have supporting data from population-based cohort trials before making salpingectomy the standard of care for sterilization. Although it will take many years to yield reliable results, any other approach is flawed.
1. Lawrie TA, Nardin JM, Kulier R, Boulvain M. Techniques for the interruption of tubal patency for female sterilisation. Cochrane Database Syst Rev. 2011.16;(2):CD003034.
2. Kindelber DW, Lee Y, Miron A, et al. Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: evidence for a causal relationship. Am J Surg Pathol. 2007;31(2):161–169.
3. Rice MS, Hankinson SE, Tworoger SS. Tubal ligation, hysterectomy, unilateral oophorectomy, and risk of ovarian cancer in the Nurses’ Health Studies. Fertil Steril. 2014;102(1):192–198.
4. Curtis KM, Mohllajee AP, Peterson HB. Regret following female sterilization at a young age: a systematic review. Contraception. 2006;73:205–210.
5. Kwon JS, McAlpine JN, Hanley GE, et al. Costs and benefits of opportunistic salpingectomy as an ovarian cancer prevention strategy. Obstet Gynecol. 2015;125(2):338–345.