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Vol. 17 No 3 | Spring 2015
Women's Health -> Q&A
Q&a: ovarian cancer risk-reducing surgery
Dr Stephen Lyons
BSc, PhD, MBBS, FRANZCOG


This article is 5 years old and may no longer reflect current clinical practice.

For the broader O&G Magazine readership, balanced answers to those curly-yet-common questions in obstetrics and gynaecology.

Q

‘My patient has requested a permanent sterilisation, but she has been reading about ovarian cancer risks and, rather than tubal clips, wants me to remove the fallopian tubes instead. What should I do?’

a

The thinking about the aetiology, morphology and behaviour of ovarian cancer has changed dramatically over the last few decades, such that the condition is now considered to be a heterogenous group of diseases.1,2 Epithelial tumours account for about 90 per cent of ovarian cancers, with the remainder comprised of germ cell and sex cord-stromal tumours. There are five main types of epithelial tumours: high-grade serous carcinoma (HGSC), endometrioid carcinoma, clear cell carcinoma, mucinous carcinoma, and low-grade serous carcinoma with relative frequencies of about 70 per cent, ten per cent, ten per cent, three per cent and less than three per cent, respectively.3 The BRCA1 and BRCA2 gene mutations were identified in the mid-1990s and have been associated with an increased risk of ovarian cancer and breast cancer. Of particular interest here, the BRCA mutations are associated with HGSC, the commonest sub-type of ovarian cancer, responsible for about 70 per cent of ovarian cancer deaths. In 2001, high-grade serous tubal intraepithelial carcinoma (STIC) was first identified in the fallopian tube fimbria, but not the ovary, of some BRCA-positive patients undergoing risk-reduction bilateral salpingo-oophorectomy.4 It is now thought that at least 60 per cent of BRCA-positive HGSC is of tubal origin. Bilateral salpingo-oophorectomy performed by the age of 40 years is thought to decrease the risk of ovarian cancer by about 80 per cent in high-risk women. Consistent with a tubal origin for many HGSCs, bilateral salpingectomy without oophorectomy by the age of 40 years in BRCA-positive women also appears to decrease the risk of ovarian cancer, by about 60 per cent.5 Hence, the benefit of risk-reduction bilateral salpingo-oophorectomy and salpingectomy has been established for women at high-risk for ovarian cancer. What is the situation for BRCA-negative women who are low-risk for the development of ovarian cancer?

The vast majority of HGSC (85–90 per cent) is sporadic; in other words, not BRCA-related. However, high-grade STIC has been identified in the fallopian tubes of BRCA-negative women undergoing salpingectomy performed for benign conditions (usually at hysterectomy), as well as at surgery for HGSC. Indeed, STIC lesions have been identified in the tubal fimbria of up to 60 per cent of a population of women untested for BRCA mutations who have HGSC, the same proportion as for a high-risk population.6 It is therefore likely that women at low-risk for ovarian cancer may also benefit from opportunistic risk-reduction bilateral salpingectomy. Unfortunately, the available information is generally from cohort and case-control studies and no randomised controlled trial (RCT) data are available. While there is no suggestion that bilateral salpingectomy should be performed routinely in low-risk women to decrease their risk of ovarian cancer, there is a trend towards performing opportunistic bilateral salpingectomy at surgery for benign gynaecological conditions (for example, hysterectomy) to decrease the risk of ovarian cancer. Hence the question, should bilateral salpingectomy be offered to women of low risk for ovarian cancer instead of tubal ligation?

Risk reduction for ovarian cancer

Tubal ligation is the commonest form of permanent contraception worldwide with high efficacy and low complication rates. In addition, data from large cohort studies also show that tubal ligation is associated with a decrease in the risk of ovarian cancer by about 25 per cent.7,8 Interestingly, hysterectomy performed in isolation (in other words, without bilateral salpingo-oophorectomy or bilateral salpingectomy) also decreases the risk of ovarian cancer, by about 20 per cent.7 The decreased incidence of ovarian cancer associated with both tubal ligation and hysterectomy is more pronounced for non-serous tumours, especially the endometrioid and clear cell sub-types, than for HGSC.8 It has been postulated that the inverse effect on non-serous tumours by tubal ligation and hysterectomy may be via a common mechanism; for example, prevention of retrograde menstruation or reduction of ovarian function owing to compromised blood supply.7

Recent population-based studies from Sweden and Denmark have confirmed the inverse effect of tubal ligation and hysterectomy on the risk of epithelial ovarian cancer and also showed, for the first time, that salpingectomy decreases the risk of epithelial ovarian cancer in the general population. Bilateral salpingectomy decreased the risk of ovarian cancer by 35–42 per cent, whereas the effect of tubal ligation was more modest (a 13–28 per cent reduction).9,10 Furthermore, a Markov Monte Carlo simulation study predicted that salpingectomy would decrease the risk of ovarian cancer by 38 per cent and 29 per cent when compared to hysterectomy and tubal ligation, respectively.11 These data showing superior reduction in ovarian cancer associated with salpingectomy would appear to support the theory that HGSC arises from STIC lesions in the fimbria, with tubal ligation and hysterectomy having a lesser effects on this aetiology. Indeed, salpingectomy may also be expected to decrease the risk of endometrioid and clear cell ovarian carcinomas, similar to tubal ligation and hysterectomy.7

Advantages and disadvantages

Advantages

As discussed above, salpingectomy appears to be associated with a reduced risk of ovarian cancer for both high-risk and low-risk populations. This effect is significantly greater than that achieved with tubal ligation.

Compared to tubal ligation, salpingectomy is associated with a lower incidence hydrosalpinx, and eliminates the need for re-operation for this indication (estimated to be about eight per cent up to 30 years post-hysterectomy).12

Compared to tubal ligation, salpingectomy has a lower failure rate and probability of subsequent ectopic pregnancy. Indeed, salpingectomy has the lowest rates of all sterilisation methods for contraception failure rate and ectopic pregnancy.2

Disadvantages

It is now well established that women at low-risk of ovarian cancer should generally retain their ovaries until at least the age of 65 years, in order to decrease mortality and morbidity related to coronary heart disease, osteoporosis-related fracture and cognitive dysfunction and dementia (see RANZCOG Statement C-Gyn 25: Managing the adnexae at the time of hysterectomy for benign gynaecological disease). Therefore, there is some concern that opportunistic salpingectomy may damage ovarian collateral circulation, resulting in premature ovarian failure. Several studies comparing laparoscopic hysterectomy to laparoscopic hysterectomy plus bilateral salpingectomy showed the addition of salpingectomy has no short-term effect (up to three months) on ovarian function and reserve as determined by anti-Mullerian hormone, follicle-stimulating hormone and oestrodiol levels, antral follicle count, mean ovarian diameter and peak systolic velocity.13,14 Although longer term follow up is necessary, these early data suggest that bilateral salpingectomy has no adverse effect on ovarian function. Furthermore, it could be postulated that early ovarian failure related to salpingectomy would only result from inadvertent damage to the ovarian circulation owing to poor surgical technique.2

Most gynaecologists are able to perform bilateral salpingectomy at caesarean section and at laparoscopy, although the procedure is more complex than for tubal ligation. The addition of salpingectomy at laparoscopic hysterectomy does not appear to significantly affect operative time, post-operative stay, time to return to normal activity or post-operative haemoglobin.14 There are, however, no prospective study data available comparing the perioperative complications associated with bilateral salpingectomy and tubal ligation. Given the data from studies comparing hysterectomy to hysterectomy plus salpingectomy, it is unlikely that there would be a significant difference in complication rates between salpingectomy and tubal ligation performed at caesarean section. At laparoscopy, however, there is at least one point of difference between the techniques as performed at open surgery. In particular, laparoscopic tubal ligation is usually performed through two port sites (one at the umbilicus for the laparoscope and another suprapubically for the clip applicator). Laparoscopic salpingectomy, on the other hand, would generally require the addition of at least one additional lateral port (to allow for a grasper and a laparoscopic energy source) and perhaps a surgical assistant (depending on the surgeon’s level of skill). Prospective comparative studies of laparoscopic tubal ligation and salpingectomy perioperative outcomes (operating time, postoperative pain, time to discharge, complications and so forth) are necessary to delineate risk-benefit profiles for these procedures.

Compared to tubal ligation, salpingectomy eliminates the chance of future tubal re-anastomosis and necessitates in vitro fertilisation if there is a change of mind regarding future childbearing.

What should I do?

The choice between salpingectomy and tubal ligation is not clear, as evidenced by recent professional body statements. For example, the Working Group Gynecological Oncology (AGO, Germany) states: ‘there is insufficient evidence to currently recommend opportunistic salpingectomy at all hysterectomies and other gynaecological procedures’.15 The American Congress of Obstetricians and Gynecologists acknowledges the likely benefit of salpingectomy on reducing the incidence of ovarian cancer, but notes: ‘the approach to hysterectomy or sterilization should not be influenced by the theoretical benefit of salpingectomy; that is, for example, a total laparoscopic hysterectomy should not be performed instead of a vaginal hysterectomy for the sole purpose of performing concomitant salpingectomy’.16 The Society of Gynecologic Oncology (USA) concluded that important ovarian cancer prevention strategies may include tubal ligation as well as opportunistic salpingectomy after childbearing is complete at the time of elective pelvic surgeries; for example, at the time of hysterectomy or as an alternative to tubal ligation.17 RANZCOG recommends: ‘consideration should be given to performing bilateral salpingectomy instead of tubal occlusive procedures for female sterilisation’ (see RANZCOG Statement C-Gyn 22: Female Sterilisation by Filshie Clip Tubal Occlusion). It is quite likely that bilateral salpingectomy, instead of tubal ligation, will be found to be in the best interests of the patient. For now, given the uncertainty about the risk-benefit profile of salpingectomy over tubal clips for permanent sterilisation, the choice should be made on a case-by-case basis. Most importantly, the patient should be included in the decision-making process.

References

  1. Kurman RJ, Shih I-M. Molecular Pathogenesis and Extraovarian Origin of Epithelial Ovarian Cancer. Shifting the Paradigm. Human Pathology. 2011 July; 42(7): 918-931.
  2. Nezhat FR, Apostol R, Nezhat C, Pejovic T. New insights in the pathophysiology of ovarian cancer and implications for screening and prevention. American Journal of Obstetrics & Gynecology. 2015 March. doi: 10.1016/j.ajog.2015.03.044 [Epub ahead of print].
  3. Prat, J. Staging classification for cancer of the ovary, fallopian tube, and peritoneum. International Journal of Gynecology and Obstetrics 2014; 124:1-5.
  4. Piek JM, van Diest PJ, Zweemer RP, Jansen JW, Poort-Keesom RJ, Menko FH. Dysplastic changes in prophylactically removed Fallopian tubes of women predisposed to developing ovarian cancer. Journal of Pathology 2001; 195(4):451-6.
  5. Kwon JS, Tinker A, Pansegrau G, McAlpine J, Housty M, McCullum M, Gilks CB. Prophylactic Salpingectomy and Delayed Oophorectomy as an Alternative for BRCA Mutation Carriers. Obstetrics & Gynecology. 2013; 121:14-24.
  6. Schenberg T, Mitchell G. Prophylactic bilateral salpingectomy as a prevention strategy in women at high-risk of ovarian cancer: a mini-review. Frontiers in Oncology. 2014 Feb; doi: 10.3389/ fonc.2014.00021.
  7. Rice MS, Hankinson SE, Tworoger SS. Tubal ligation, hysterectomy, unilateral oophorectomy, and risk of ovarian cancer in the Nurses’ Health Studies. Fertility and Sterility. 2014 July; 102(1): 192-198.
  8. Sieh W, Salvador S, McGuire V, Palmieri Weber R, Terry KL, Rossing MA, Risch H, Wu AH, Webb PW, Moysich K, Doherty JA, Felberg A, Miller D, Jordan SJ. Australian Cancer Study (Ovarian Cancer), Australian Ovarian Cancer Study Group, Goodman MT, Lurie G, Chang-Claude J, Rudolph A, Kruger Kjær S, Jensen A, Høgdall E, Bandera EV, Olson SH, King MC, Rodriguez- Rodriguez L, Kiemeney LA, Marees T, Massuger LF, van Altena AM, Ness RB, Cramer DW, Pike MC, Leigh Pearce C, Berchuck A, Schildkraut JM, Whittemore AS. Tubal ligation and risk of ovarian cancer subtypes: a pooled analysis of case-control studies. International Journal of Epidemiology. 2013; 42:579-589.
  9. Falconer H, Yin L, Grönberg H, Altman D. Ovarian cancer risk after salpingectomy: a nationwide population-based study. Journal of the National Cancer Institute. 2015 Feb; 107(2) doi: 10.1093/jnci/dju410.
  10. Madsen C, Baandrup L, Dehlendorff C, Kjaer SK. Tubal ligation and salpingectomy and the risk of epithelial ovarian cancer and borderline ovarian tumors: a nationwide case-control study. Acta Obstetrica et Gynecologica Scandinavia. 2015 Jan; 94(1):86-94.
  11. Kwon JS, McAlpine JN, Hanley GE, Finlayson SJ, Cohen T, Miller DM, Gilks CB, Huntsman DG. Costs and benefits of opportunistic salpingectomy as an ovarian cancer prevention strategy. Obstetrics & Gynecology. 2015 Feb; 125(2):338-45.
  12. Morse AN, Schroeder CB, Magrina JF, et al. The risk of hydrosalpinx formation and adnexectomy following tubal ligation and subsequent hysterectomy: a historical cohort study. American Journal of Obstetrics & Gynecology. 2006; 194:1273-6.
  13. Findley AD, Siedhoff MT, Hobbs KA, et al. Short-term effects of salpingectomy during laparoscopic hysterectomy on ovarian reserve: a pilot randomized controlled trial. Fertility and Sterility. 2013; 100:1704-8.
  14. Morelli M, Venturella R, Mocciaro R, et al. Prophylactic salpingectomy in premenopausal low-risk women for ovarian cancer: primum non nocere. Gynecological Oncology. 2013; 129:448-51.
  15. Polcher M, Hauptmann S, Fotopoulou C, Schmalfeldt B, Meinhold-Heerlein I, Alexander Mustea A, Runnebaum I, Sehouli J. Opportunistic salpingectomies for the prevention of a high-grade serous carcinoma: a statement by the Kommission Ovar of the AGO. Archives of Gynecology and Obstetrics. 2015: 292:231–234.
  16. Committee on Gynecologic Practice. Committee opinion no. 620: Salpingectomy for ovarian cancer prevention. Obstetrics & Gynecology. 2015 Jan; 125(1):279-81.
  17. Walker JL, Powell CB, Chen LM, Carter J, Bae Jump VL, Parker LP, Borowsky ME, Gibb RK. Society of Gynecologic Oncology recommendations for the prevention of ovarian cancer. Cancer. 2015 Mar; doi: 10.1002/cncr.29321. [Epub ahead of print].

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