Surgical prevention of epithelial ovary cancer without oophorectomy: changing the future Ovarian Cancer and Us OVARIAN CANCER and US Ovarian Cancer and Us

Blog Archives: Nov 2004 - present

#ovariancancers



Special items: Ovarian Cancer and Us blog best viewed in Firefox

Search This Blog

Wednesday, July 13, 2016

Surgical prevention of epithelial ovary cancer without oophorectomy: changing the future



Editorial (open access)

 Published online: 12 Jul 2016

 There is a need for prospective studies aimed at evaluating opportunistic bilateral salpingectomy in women without BRCA mutations, in order to obtain more evidence in this regard. In addition, the number of women to be treated with salpingectomy remains to be determined in order to prevent one sporadic EOC and assess its global impact on economic costs.
 
Ovarian cancer is an important oncologic cause of mortality in developed countries. This trend has been maintained during decades and, as life expectancy increases, the number of cases will also. The pivotal cause of such a negative scenario is related to the ease with which this entity disseminates into the abdominal cavity without presenting specific symptoms or complaints. Certain gene mutations, such as BRCA-1 and BRCA-2, have been related to an increased risk of both ovarian and breast cancer. These patients have classically been managed by bilateral salpingo-oophorectomy (to reduce ovarian cancer risk) and mastectomy (to reduce breast cancer risk). Adnexal specimens from asymptomatic women with germline BRCA mutations show the presence of early Fallopian tube carcinomas or serous tubal intraepithelial carcinomas (STICs)1. These tubal lesions have also been reported among incidental non-uterine carcinomas2, suggesting that STICs are precursors of extrauterine, high-grade, serous carcinomas (ovarian and peritoneal cancers). These STICs are preferentially located at the site of the Fallopian fimbriae, which is closely related to the ovarian surface.
An important issue in analysis is whether bilateral salpingectomy has better or worse global results in the management of women with BRCA mutations as compared to the conventional salpingo-oophorectomy. Harmsen and colleagues3 determined a small difference in cumulative ovarian cancer risk among women of various ages and carrying BRCA 1/2 mutations when risk-reducing salpingectomy with oophorectomy delayed for several years after (two-step procedure) was compared to one-step conventional risk-reducing salpingo-oophorectomy. On the other hand, the available evidence suggests that salpingo-oophorectomy after childbearing is likely also to reduce breast cancer risk despite short-term menopausal hormone therapy (MHT)4. The evidence regarding consequences of long-term MHT in this population is limited5. Nevertheless, prospective clinical trials are ongoing to evaluate the two-step procedure for preventing ovarian cancer6. This two-step approach seeks to avoid earlier estrogenic deficiency and MHT use in an attempt to reduce severe menopause-related symptoms, vaginal dryness, painful intercourse and future increased risk of osteoporosis and cardiovascular disease. At the same time, the presence of STICs in the Fallopian tubes, surgical complications, quality of life and patient satisfaction will also be assessed.
Non-BRCA-related (sporadic) ovarian cancer includes a wide variety of histological types of malignant diseases, although the most prevalent are epithelial ovarian cancers (EOCs). The majority of EOC cases occur in women without hereditary risk factors in their second half of life, and there are no effective screening procedures7. The lack of specific ovarian symptoms or vague symptoms – such as bloating, digestive symptoms or indigestion – are common, and are easily missed or misinterpreted as the results of an advanced peritoneal dissemination, even in the absence of significant ovarian tumor growth. Hence, women are usually diagnosed and treated during clinical stages III or IV when the outcome is associated with high mortality rates. A combination of ultrasound explorations and biochemical marker measurements (CA 125, HE4, serum folate receptor alpha, immunoglobulins and other proteins) has been proposed to improve early diagnosis among women with low ovarian cancer risk; despite this, these tests have not decreased the mortality rate and render too many false-positive results, which in turn lead to unnecessary surgeries8,9. Microarray methods and nanotechnology are also being explored in pilot studies and in small populations, using blood, uterine and Fallopian tube fluids for the early diagnosis and prognostic evaluation of ovarian cancer-related conditions. However, further studies are needed in this area.
There are some clinical circumstances which may reduce non-hereditary-related EOC risk, including the use of various contraceptive methods and/or surgical interventions. Oral contraceptives may reduce the risk of EOC10, perhaps by decreasing the amount of menstrual content which could stimulate Fallopian carcinogenesis. Fallopian tubal ligation and hysterectomy have also been associated with reduced ovarian cancer risk11. The results from two cohorts of the Nurses’ Health Study reported that tubal ligation reduces ovarian cancer risk, particularly non-serous cancer, when carried out before the age of 3512. A large prospective study reported that tubal ligation confers different degrees of benefits in the prevention of ovarian cancer according to histological types (serous, endometrioid, mucinous and clear cell). The prevention of ovarian cancer was greater for high-risk serous, endometrioid and clear-cell tumors while the effect was nil for mucinous type cancer13. The results from a population-based study suggest that salpingectomy may confer a higher reduction of ovarian cancer risk than other sterilization methods14.
Hysterectomy alone (retaining Fallopian tubes and ovaries) may also contribute to reducing future ovarian cancer risk11,12. Opportunistic bilateral salpingectomy during surgery for benign conditions of the genital tract (i.e. uterine myomata) or sterilization has emerged as a probable way of reducing future non-hereditary EOC risk15. Madsen and colleagues16, reporting on a Danish cohort, showed the beneficial effects of tubal salpingectomy in decreasing EOC risk, with the greatest reduction being for endometrioid cancer. Based on the new scenario that ovarian cancer may probably initiate at the Fallopian tubes, opportunistic bilateral salpingectomy in young women may confer the advantage of removing the possible site of origin of the cancer, while maintaining the ovaries, and hence decreasing the side-effects of oophorectomy. This approach may also reduce cases related to inflammatory conditions of the Fallopian tubes. Although the evidence is limited, it seems that opportunistic salpingectomy may reduce the prevalence of ovarian cancer; hence, it should be performed during surgery for benign pelvic or genital conditions, and also in women who do not expect to have further children, instead of just tubal ligation. Prophylactic salpingectomy during laparoscopic, laparotomic or vaginal hysterectomy does not increase morbidity or severity of menopausal symptoms17–19.
There is a need for prospective studies aimed at evaluating opportunistic bilateral salpingectomy in women without BRCA mutations, in order to obtain more evidence in this regard. In addition, the number of women to be treated with salpingectomy remains to be determined in order to prevent one sporadic EOC and assess its global impact on economic costs.

Conflict of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.

References

  • 1. Cass I, Walts AE, Barbuto D, Lester J, Karlan B. A cautious view of putative precursors of serous carcinomas in the fallopian tubes of BRCA mutation carriers. Gynecol Oncol 2014;134:492–7 [CrossRef], [PubMed], [Web of Science ®]
  • 2. Gilks CB, Irving J, Köbel M, et al. Incidental nonuterine high-grade serous carcinomas arise in the fallopian tube in most cases: further evidence for the tubal origin of high-grade serous carcinomas. Am J Surg Pathol 2015;39:357–64 [CrossRef], [PubMed], [Web of Science ®]
  • 3. Harmsen MG, IntHout J, Arts-de Jong M, et al. Salpingectomy with delayed oophorectomy in BRCA1/2 mutation carriers: Estimating ovarian cancer risk. Obstet Gynecol 2016;127:1054–63 [CrossRef], [PubMed], [Web of Science ®]
  • 4. Rebbeck TR, Friebel T, Wagner T, et al.; PROSE Study Group. Effect of short-term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol 2005;23:7804–10 [CrossRef], [PubMed], [Web of Science ®]
  • 5. Marchetti C, Iadarola R, Palaia I, et al. Hormone therapy in oophorectomized BRCA1/2 mutation carriers. Menopause 2014;21:763–8 [CrossRef], [PubMed], [Web of Science ®]
  • 6. NIH. National Cancer Institute. Compliance rate of delayed oophorectomy in patients with BRCA gene mutation undergoing salpingectomy. Clinical Trial 751356 http://www.cancer.gov/about-cancer/treatment/clinical-trials/search/view?cdrid =751356 (accessed 18 May 2016)
  • 7. Pérez-López FR, Chedraui P, Troyano-Luque JM. Peri- and post-menopausal incidental adnexal masses and the risk of sporadic ovarian malignancy: new insights and clinical management. Gynecol Endocrinol 2010;26:631–43 [Taylor & Francis Online], [PubMed], [Web of Science ®]
  • 8. Jacobs IJ, Menon U, Ryan A, et al. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet 2016;387:945–56 [CrossRef], [PubMed], [Web of Science ®]
  • 9. Sölétormos G, Duffy MJ, Othman Abu Hassan S, et al. Clinical use of cancer biomarkers in epithelial ovarian cancer: Updated Guidelines from the European Group on Tumor Markers. Int J Gynecol Cancer 2016;26:43–51 [CrossRef], [PubMed], [Web of Science ®]
  • 10. Havrilesky LJ, Moorman PG, Lowery WJ, et al. Oral contraceptive pills as primary prevention for ovarian cancer: a systematic review and meta-analysis. Obstet Gynecol 2013;122:139–47 [CrossRef], [PubMed], [Web of Science ®]
  • 11. Rice MS, Murphy MA, Tworoger SS. Tubal ligation, hysterectomy and ovarian cancer: A meta-analysis. J Ovarian Res 2012;5:13 [CrossRef], [PubMed], [Web of Science ®]
  • 12. Rice MS, Hankinson SE, Tworoger SS. Tubal ligation, hysterectomy, unilateral oophorectomy, and risk of ovarian cancer in the Nurses' Health Studies. Fertil Steril 2014;102:192–8.e3 [CrossRef], [PubMed], [Web of Science ®]
  • 13. Gaitskell K, Green J, Pirie K, Reeves G, Beral V; on behalf of the Million Women Study Collaborators. Tubal ligation and ovarian cancer risk in a large cohort: Substantial variation by histological type. Int J Cancer 2016;138:1076–84 [CrossRef], [PubMed], [Web of Science ®]
  • 14. Lessard-Anderson CR, Handlogten KS, et al. Effect of tubal sterilization technique on risk of serous epithelial ovarian and primary peritoneal carcinoma. Gynecol Oncol 2014;135:423–7 [CrossRef], [PubMed], [Web of Science ®]
  • 15. Falconer H, Yin L, Grönberg H, Altman D. Ovarian cancer risk after salpingectomy: a nationwide population-based study. J Natl Cancer Inst 2015;107:dju410 [CrossRef], [PubMed]
  • 16. 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 Obstet Gynecol Scand 2015;94:86–94 [CrossRef], [PubMed], [Web of Science ®]
  • 17. Findley AD, Siedhoff MT, Hobbs KA, et al. Short-term effects of salpingectomy during laparoscopic hysterectomy on ovarian reserve: a pilot randomized controlled trial. Fertil Steril 2013;100:1704–8 [CrossRef], [PubMed], [Web of Science ®]
  • 18. Minig L, Chuang L, Patrono MG, Cárdenas-Rebollo JM, García-Donas J. Surgical outcomes and complications of prophylactic salpingectomy at the time of benign hysterectomy in premenopausal women. J Minim Invasive Gynecol 2015;22:653–7 [CrossRef], [PubMed], [Web of Science ®]
  • 19. Robert M, Cenaiko D, Sepandj J, Iwanicki S. Success and complications of salpingectomy at the time of vaginal hysterectomy. J Minim Invasive Gynecol 2015;22:864–9 [CrossRef], [PubMed], [Web of Science ®]

0 comments :

Post a Comment

Your comments?