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1. Background

Updated May 8, 2018

Ovary - Epithelial Carcinoma (EOC) including Fallopian Tube Cancer and Primary Peritoneal Cancer

Ovarian cancer is the 7th most common malignancy in British Columbia women with a crude incidence rate of 17.3 per 100,000. The incidence rate has remained relatively stable over the past 30 years with a 5-year relative survival of about 35%. Epithelial ovarian carcinomas (EOC) account for ~90% of all ovarian malignancies. During the last decade it has become apparent that EOC encompasses 5 distinct diseases, with different presentations (age of development, distribution of disease), response to chemotherapy, prognosis, molecular features, and site of origin1, 2. While these carcinomas share a common site of tumor growth in the ovary, they represent diverse diseases entities. This has driven the move towards more histotype specific management strategies.  

High-grade serous carcinoma (HGSC) is the most common (70% of EOC) histological subtype usually presenting at advanced stage and accounting for the majority of deaths from ovarian cancer. It is believed that the majority of HGSC originate in the distal fallopian tube epithelium and that this histotype is most closely associated with hereditary breast and ovarian cancer syndrome (e.g. BRCA1 or BRCA2 mutations). Fallopian tube carcinoma was previously considered a separate disease site, but the understanding that HGSC of fallopian origin often appear as a dominant mass on the ovary, there is a move to label these tumours “tubo-ovarian”, “pelvic serous”, or “Mullerian serous” (non-uterine) carcinomas3, 4. The two next most common types of EOC, clear cell (10%) and endometrioid (10%), may arise from endometriosis that has implanted on the ovaries or in the peritoneal cavity and undergone malignant transformation. Low grade serous carcinoma (LGSC) and mucinous carcinoma comprise the remaining 2 types of EOC, and are much more rare (<5% each). LGSC may arise from borderline serous carcinomas (tumours of low malignant potential).  

1.1 Predisposing Risk Factors 

Established risk factors for EOC are reproductive and genetic in nature. An appreciation of the distinct subtypes of EOC has provided a new framework through which to interpret risk factors in ovarian cancer.  

Reproductive risk factors

Higher risk of ovarian cancer has been observed in women with no children or with low numbers of live births. Risk factors that can promote changes at the fallopian tube epithelium include ascending infections (e.g., pelvic inflammatory disease) and retrograde menstruation. Endometriosis is also a well-known risk factor for ovarian cancers, but most strongly associated with clear cell and endometrioid subtypes. Interventions that prevent passage from the lower genital tract or uterus via the fallopian tube to the ovary and peritoneal cavity (e.g., tubal ligation) have shown substantial risk reduction, most notably in clear cell and endometrioid histotypes. These findings support the important role the fallopian tube plays in the development of ovarian cancer, not only as the site of origin for the majority of high-grade serous carcinomas but also as a conduit for inflammatory stimuli including endometriosis and infection.

Genetic risk factors

Family history of breast and ovarian cancer has long known to be associated with risk of disease, and plays a much more profound role in ovarian HGSC with an estimated 1 in 5 women with HGSC harbouring germline BRCA1 or BRCA2 mutations. Clear cell and endometrioid tumors can be associated with Lynch syndrome (also referred to as Hereditary Non-Polyposis Colorectal Carcinoma [HNPCC]), which is associated with increased lifetime risks of developing colorectal carcinoma, endometrial carcinoma, ovarian cancer and other primary tumors. 

1.2 Screening/ Early Detection

There are no screening tests proven to detect ovarian cancer at an early stage and reduce the number of women who die from this disease. Screening modalities tested have included pelvic examination, CA125 and ultrasound and thus far three well executed international clinical trials on screening for ovarian cancer (ultrasound +/- CA125) have failed to demonstrate a significant benefit in survival from these interventions and have yielded an unacceptably high rate of false positive tests leading to unnecessary surgery5, 6, 7. Therefore, ovarian cancer screening is currently not recommended by either the Society of Gynecologic Oncology of Canada, or the American College of Obstetrics and Gynecology.  

1.3 Prevention

1) Opportunistic salpingectomy for average-risk women: For women who are undergoing any pelvic surgery and who have met their reproductive needs, consideration should be given to  removal of the fallopian tubes.

Rationale: Given the lack of effective screening strategies, opportunities for prevention should be considered.  Given that the fallopian tube plays a key role in cancer development, both as a site of origin (e.g. HGSCs) and as a conduit for endometriosis (which is associated with clear cell and endometrioid cancers), the fallopian tubes can be removed in women who are undergoing pelvic surgery and no longer need their tubes for reproductive purposes. Titled “opportunistic salpingectomy” this options is directed at women at ‘low-risk’ (i.e. the general population, women not know to have an inherited mutation) for developing ovarian cancer and to be performed at the time of hysterectomy for benign conditions or when permanent sterilization is being done (e.g., salpingectomy in lieu of tubal ligation). 

Uptake and short-term safety of this strategy have been demonstrated8, 9. Opportunistic salpingectomy does not appear to increase perioperative morbidity or risk of premature menopause; however, long-term outcomes are still unknown.  Salpingectomy (for other indications such as sterilization) appears to be associated with decreased ovarian cancer risk, based on population-based data and case-control studies10, 11, 12.

2) Risk-reducing surgery in high-risk women: Bilateral Removal of ovaries and fallopian tubes by age 40 or when childbearing is complete. Salpingectomy alone in this population is unproven but can be considered in individuals who refuse standard of care.

Bilateral removal of the fallopian tubes and ovaries is the standard recommendation for BRCA1/BRCA2 mutation carriers who have completed childbearing and wish to reduce their future risk of ovarian and fallopian tube cancers. However, surgical menopause following bilateral BSO (BSO) includes cardiovascular disease, bone loss, and other comorbidities. Because the majority of BRCA-associated cancers appear to arise in the fallopian tubes, it would seem reasonable to offer salpingectomy as a risk-reducing procedure to these high-risk women. However, there are 2 compelling reasons to recommend removal of the ovaries: (1) some BRCA-associated cancers arise primarily in the ovaries, and (2) premenopausal oophorectomy reduces breast cancer risk by approximately 50%.  Salpingectomy alone in this population should be reserved only for individuals who decline standard of care.  

3) Chemoprevention strategies such as oral contraceptive pills may also be considered and are believed to be effective in reducing ovarian/fallopian tube cancer risk by about 50% if used for 5 years by both low-risk and high-risk women13, 14. The caveat is that there may be an increased risk of breast cancer associated with oral contraceptives in BRCA1 mutation carriers15

SOURCE: 1. Background ( )
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