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Cancer
Vol. 14 No 1 | Autumn 2012
Feature
Risk-reducing surgery


This article is 8 years old and may no longer reflect current clinical practice.

Prophylactic risk-reducing surgery is being performed more frequently as women and their medical practitioners become more aware of the genetic and hereditary factors involved in some gynaecological malignancies.

Even before the identification of the BRCA1 gene, in 1994, and BRCA2, in 1995, linkage studies had clearly shown a heritable risk factor in some cases of ovarian and breast cancer. This has been extended with the identification of mis-match repair (MMR) gene abnormalities in Lynch Syndrome and the increased risk of ovarian and endometrial cancer in this condition.

The mechanics of risk-reducing surgery (RRS) are only a minor part of the overall treatment of women being counselled about this intervention. In general, a woman who perceives her risk of gynaecological malignancy is sufficiently high to warrant surgical intervention should:

  • have a thorough family history taken, which includes male relatives; and
  • consider referral to a Familial Cancer Clinic (FCC) to try and define the actual risk, not only for the woman herself, but also for other family members.

This may include specific genetic testing, but there are many situations where this may not be possible or the results are uninformative. However, the involvement of a FCC does broaden the perspective by looking at other associated malignancies and options for screening and early intervention for the patient and her family. A comprehensive overview of recommendations for the management of women at high risk of ovarian cancer is available at the Cancer Australia website.

Initial discussions with a woman about RSS will often focus on the surgery itself. What should be removed and how will this be performed? An essential part of the surgery is careful inspection of the ‘at risk’ peritoneal cavity and complete removal of the at-risk structures. Numerous case reports of malignancy in residual ovarian tissue in women who had undergone oophorectomy highlight the importance of complete removal of all ovarian and extra-uterine fallopian tube. This effectively means a vaginal-only approach to the surgery is inadequate. There is no evidence to support either laparoscopy or laparotomy as being superior in terms of malignancy risk reduction and the decision as to the mode of surgery should be made on the basis of the usual risk factors and operator experience. The mechanics of surgery are only a small part of the process of RRS in high-risk or potentially high-risk women. Apart from discussing the nature, aims and risks of the surgical procedure, many other issues will need to be clarified prior to performing any surgical procedure.

Is a hysterectomy required?

Despite initial concerns about an increased risk of serous endometrial cancer in women with BRCA mutation, this has not been shown to be true in subsequent studies. There is no current evidence to support routine prophylactic hysterectomy as an effective part of RRS for potential high-risk or known BRCA mutation carriers.

As Lynch Syndrome is associated with more than 50 per cent life-time risk of endometrial cancer and ten per cent lifetime risk of ovarian cancer, hysterectomy is an essential component of RRS in this condition.1

What is the risk of malignancy after RRS?

Removal of the tubes and ovaries is associated with a marked reduction in the risk of ovarian cancer. Domchek et al have reported a marked reduction in gynaecological cancer and death in women with a BRCA mutation undergoing RRS.2 Rarely, primary peritoneal cancer can occur after RRS. The risk of primary peritoneal cancer after gynaecological RRS appears to be approximately one per cent and there is no evidence that screening for this condition after RRS is effective or beneficial.1

There is limited data published on the efficacy of RRS in Lynch Syndrome, but what is available supports a marked reduction in the frequency of gynaecological cancer after RRS.1

A secondary effect of RRS with removal of the ovaries in pre-menopausal women with BRCA mutation is a significant reduction (approximately 50 per cent) in the risk of breast cancer.1,3

Several studies on prophylactic bilateral salpingo-oophorectomy (BSO) in women with BRCA mutations have reported occult cancer in four to 12 per cent of cases. It is therefore important to explain that a small number of women undergoing RRS may require further treatment.

Management of menopausal symptoms

Women with surgically induced menopause more commonly report night sweats, sleep disturbance, hot flushes and decreased libido and have significantly more severe vasomotor symptoms than women who go through natural menopause.4 However, Finch et al reported that physical and mental health-related quality of life for most women did not deteriorate after RRS in BRCA mutation carriers.5

Hormone replacement therapy (HRT) appears to control some, but not all, of these symptoms. There is no apparent increase in risk of breast cancer in BRCA1/2 mutation carriers, unaffected by breast cancer, who take short-term HRT after RRS performed before the age of 50 years compared to those who do not take HRT. Domcheck reported that HRT following RRS for BRCA mutation carriers was not associated with an increased risk of breast cancer, however, the length of follow up is limited.6

There is no reason to believe that non-hormonal measures to control menopausal symptoms after RRS would have different efficacy or risks compared to those seen in the general population. Longer term implications of premature menopause and possible interventions to prevent or deal with these problems should also be clearly explained and, if necessary, implemented.

Despite the effects of RRS on hormonal function in premenopausal women, follow up at 12 months suggests that less than five per cent regret the decision to proceed with surgery and the reduction in anxiety about developing ovarian cancer was a major factor in this overall level of satisfaction.7

Timing of surgery

The risk of ovarian cancer in BRCA1 carriers starts to increase from the age of 40 years and several years later for BRCA2 carriers. RRS should be considered from the age of 40 years and include complete removal of the extra-uterine component of both fallopian tubes as well as ovaries.

The beneficial effects of RRS on the overall reduction in breast cancer risk are seen only in premenopausal women and are most apparent when RRS occurs at about 40 years.

Lynch Syndrome is associated with an increasing risk of endometrial cancer from the mid 30s and ovarian cancer from the early 40s. There is no evidence to support screening for endometrial cancer in Lynch Syndrome so RRS to remove the uterus, tubes and ovaries should be considered from the mid 30s.

Our understanding of the pathogenesis of ovarian cancer has changed markedly in recent years and we are now aware that many supposed ovarian cancers probably arise in the fimbrial part of the fallopian tube.8 Microscopic malignancy identified at the time of prophylactic BSO in BRCA mutation carriers appears to show that a significant number (50–60 per cent) of high-grade serous tumours arise in the fimbria without involvement of the ovary.9 This finding has led to some speculation that prophylactic salpingectomy may be appropriate RRS but there is no data to support this procedure as being equivalent to prophylactic BSO at this time.

These recent findings have significant implications for clinical practice for both the surgeon and pathologist. The possibility that a microscopic tumour may be present in the delicate fimbrial tissue means that tubes and ovaries need to be handled with care during the operative procedure and removed intact to allow for thorough pathological examination. Morcellation of tubes and ovaries during delivery through laparoscopic ports should be avoided.

The pathologist should be made aware of the reason for the prophylactic surgery. Occult cancers involving the tubes and/ovaries will frequently go unrecognised unless ultra sectioning of the specimens is undertaken.10 This will only occur if the gynaecologist informs the pathologist of the reason for the surgery. The finding of an occult tubal or ovarian cancer has significant impact on the woman’s need for further treatment and ultimate prognosis.

RRS for gynaecological malignancy is a far more complex event than just removing the ‘at risk’ organs.11 The treating gynaecologist should never regard this as just a technical exercise and time must be spent with the patient and often her family explaining the reason for surgery, the benefits and risk of intervention and ensuring the long-term sequelae are dealt with adequately.

References

  1. Schmeler KM, Lynch HT, Chen LM et al. Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N Engl J Med.2006 Jan 19;354(3):261-9.
  2. Domchek S, Friebel T, Singer CF et al. Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA. 2010;304(9):967-7.
  3. 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(2):80-7.
  4. Benshushan A, Rojansky N, Chaviv M et al. Climacteric symptoms in women undergoing risk reducing bilateral salpingo-oophorectomy.Climacteric. 2009;12(5):404-9.
  5. Finch A, Narod SA. Quality of life and health status after prophylactic salpingo-oophorectomy in women who carry a BRCA mutation: A review. Maturitas. 2011 Nov;70:261-5.
  6. Domchek S M et al. Is hormone replacement therapy (HRT) following risk-reducing salpingo-oophorectomy (RRSO) in BRCA1 (B1)- and BRCA2 (B2)-mutation carriers associated with an increased risk of breast cancer? ASCO Annual Meeting 2011. J Clin Oncol 29: 2011(suppl; abstr 1501).
  7. Madalinska JB, Hollenstein J, Bleiker E et al. Quality-of-life effects of prophylactic salpingo-oophorectomy versus gynecologic screening among women at increased risk of hereditary ovarian cancer. J Clin Oncol. 2005;23(28):6890-8.
  8. Kurman RJ, Shih IeM. Molecular pathogenesis and extra-ovarian origin of epithelial ovarian cancer—shifting the paradigm. Hum Pathol. 2011 Jul;42(7):918-31.
  9. Powell CB, Chen LM, McLennan J 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 Jul;21(5):846-51.
  10. Rabban JT, Krasik E, Chen LM et al. Multistep level sections to detect occult fallopian tube carcinoma in risk-reducing salpingo-oophorectomies from women with BRCA mutations: implications for defining an optimal specimen dissection protocol. Am J Surg Pathol.2009 Dec;33(12):1878-85.
  11. Recommendations for management of women at high risk of ovarian cancer. A clinical practice guideline developed by national breast and ovarian cancer centre (NBOCC)* September 2011 Incorporates published evidence to April 2010. http://guidelines.nbocc.org.au/guidelines/high_risk_ovarian/.

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