The incidence of epithelial ovarian cancer in women aged 40 years and younger is 3–17%. The management of these women is challenging and requires balancing the need to treat epithelial ovarian cancer adequately and preserving reproductive potential. Fertility-sparing surgery, especially for early stage epithelial ovarian cancer, seems to be associated with equivalent clinical and cancer outcomes while preserving reproductive potential. A complete staging and cytoreductive procedure retaining the uterus, and at least one grossly normal ovary, is the minimum recommended procedure. Adjuvant chemotherapy with a platinum-taxane combination is recommended as clinically indicated, and is associated with better cancer and survival outcomes. Adjuvant treatment does not seem to increase the risk of congenital anomalies in subsequent pregnancies. Targeted therapy and ovarian cryopreservation are largely experimental and cannot be recommended as part of the clinical standard of care.
Introduction
Epithelial ovarian cancer is a common gynaecologic cancer in developed countries, and is either the most common or second most common gynaecologic malignancy. Age-standardised risk ranges from 7–17 per 100,000 population per year.
Epithelial ovarian cancer accounts for up to 90% of all ovarian cancer. Evidence suggests that epithelial ovarian tumours develop along two distinct molecular pathways leading to different clinical presentations and end points. Type I tumours arise from the ovarian epithelium and inclusions of the germ cell layers of the Müllerian system, and are thought to give rise to endometrioid, mucinous, clear cell and well-differentiated serous tumours. The tumourigenesis of these lesions is often more indolent and has been postulated to be the result of ‘multi-hit oncogenesis’. Type II tumours are thought to arise from Fallopian tubular epithelial origins, which give rise to poorly differentiated serous carcinomas. These are thought to be the product of p53 mutations. These tumours tend to be more clinically aggressive and account for a larger proportion of widely metastatic ovarian cancers. Epithelial ovarian cancer spreads primarily by exfoliating from the primary organ to seed the entire peritoneal cavity and alternatively by lymphatic spread via the retroperitoneal lymph nodes. Because of the primary mode of spread and the lack of distinct symptomatology in early disease, multiple organ systems are usually involved when a diagnosis of an ovarian malignancy is made.
The standard of care for the optimal treatment of metastatic epithelial ovarian cancer involves surgical debulking of all visible or gross disease followed by adjuvant combination chemotherapy with a platinum and a taxane. The uterus, adnexae and pelvic peritoneum are often involved in bulky pelvic disease, which is removed en bloc along with involved portions of other intraperitoneal organs. As the peak age incidence of epithelial ovarian cancer is in the fifth and sixth decades of life, and fertility is no longer a consideration, removal of the uterus, fallopian tubes and ovaries has been accepted as a necessary part of the standard surgical regimen.
The incidence of epithelial ovarian cancer in women aged 40 years and younger has been reported to be between 3 and 17%. Demographically, women in countries in which epithelial ovarian cancer incidence is highest are also the most likely to delay childbearing, and these women will most likely be interested in retaining their fertility. The prognosis that follows a particular treatment course will also be an important consideration to women in this age group. The confluence of these factors creates the dilemma that confronts cancer specialists who have to provide care to women who have a diagnosis of epithelial ovarian cancer and who may want to retain their fertility. Although the standard of care for epithelial ovarian cancer is supported by ample evidence, considerably fewer data are available to guide the management of epithelial ovarian cancer in a woman of reproductive age in whom fertility is to be preserved. This review of the available literature, specifically of recent publications, will hopefully serve as a guide to providing sound clinical care to preserving fertility in women living with epithelial ovarian cancer ( Table 1 ).
| Study | Year | N | Median age (years) | Stage | N | % | Adjuvant | Recurrence Disease-free survival | Mortality Overall survival | Median follow up (months) | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N | % | N | % | N | % | ||||||||
| Kajiyama et al. | 2011 | 74 | ≤ 40 | IA IB IC | 36 1 37 | 48.6 1.4 50 | 54 Platinum and taxane Platinum-based | 73 29.7 43.2 | ? | 87.9 | ? | 90.8 | 62.5 |
| Hu et al. | 2011 | 94 | 28.3 | IA IB IC II III | 46 8 28 1 11 | 48.9 8.5 29.8 1.1 11.7 | 48; all stage IB and above treated with platinum-based adjuvant chemotherapy | 51% | 9; most recurrences in stages II and III | 91.4 | ? | 92.3% | 58.7 |
| Schlaerth et al. | 2009 | 20 | 27 | IA IC | 11 9 | 55 45 | 10; Oral alkylating agent 2 Platinum-based chemotherapy 8 | 50 10 40 | 3 | 84 | 3 | 84 | 122 |
| Wright et al. | 2009 | 432 | < 50 | IA IC | 370 62 | 85.7 14.4 | NA | NA | NA | NA | ? | 94 | NA |
| Park et al. | 2008 | 62 | 26 | IA IB IC II III | 36 2 21 1 2 | 58.1 3.2 33.9 1.6 3.2 | 48 | 77.4 | ? | 80 | ? | 88 | 56 |
The management of epithelial ovarian cancer in young women
In stage I epithelial ovarian cancer, irrespective of grade of tumour, women who undergo fertility-sparing surgery can expect to have the same overall survival and disease-free survival as women undergoing standard surgical treatment. In the management of FIGO Stage I epithelial ovarian cancer, fertility-sparing surgery is an option.
The Fertility Task Force of the European Society of Gynaecologic Oncology laid out five considerations in the conservative management of epithelial ovarian cancer : (1) fertility-sparing surgery should be discouraged in women older than 40 years of age. The fertility rates in this group of women are low and the main objective of conservative management is to promote subsequent fertility; (2) full disclosure to the woman of possible cancer outcomes and fertility outcomes of conservative management; (3) patient engagement and co-operation in complying with the follow-up regimen; (4) histological diagnosis should be clearly made and preferably by a gynaecologic pathologist. This is important as histological features such as subtype and grade are major prognostic factors in epithelial ovarian cancer; and (5) the surgical findings of exploratory surgery should be described exhaustively to provide a clear clinical picture of the state and extent of disease at the time of diagnosis. This is important to prognosis and in guiding management.
The management of epithelial ovarian cancer in young women
In stage I epithelial ovarian cancer, irrespective of grade of tumour, women who undergo fertility-sparing surgery can expect to have the same overall survival and disease-free survival as women undergoing standard surgical treatment. In the management of FIGO Stage I epithelial ovarian cancer, fertility-sparing surgery is an option.
The Fertility Task Force of the European Society of Gynaecologic Oncology laid out five considerations in the conservative management of epithelial ovarian cancer : (1) fertility-sparing surgery should be discouraged in women older than 40 years of age. The fertility rates in this group of women are low and the main objective of conservative management is to promote subsequent fertility; (2) full disclosure to the woman of possible cancer outcomes and fertility outcomes of conservative management; (3) patient engagement and co-operation in complying with the follow-up regimen; (4) histological diagnosis should be clearly made and preferably by a gynaecologic pathologist. This is important as histological features such as subtype and grade are major prognostic factors in epithelial ovarian cancer; and (5) the surgical findings of exploratory surgery should be described exhaustively to provide a clear clinical picture of the state and extent of disease at the time of diagnosis. This is important to prognosis and in guiding management.
Clinical considerations
Age at diagnosis as a prognostic factor
Thigpen et al. looked specifically at age as a prognostic factor in epithelial ovarian cancer. Six studies by the Gynaecologic Oncology Group in advanced ovarian cancer with a pooled database of more than 2000 women were analysed for important prognostic factors, and specifically for age as a determinant of eventual clinical outcome. Women older than 69 years of age had a poorer prognosis than younger women, having corrected for stage, residual disease and performance status.
One of the early studies looking at epithelial ovarian cancer in reproductive age women was published by Duska et al. They studied clinical outcomes of epithelial ovarian cancer in women younger than 40 years. One-half of the women in the study group had borderline tumours and one-half had carcinoma. As expected, women with borderline ovarian tumours tended to have early stage disease, were able to have fertility-sparing surgery (54.3%) with optimal cytoreduction (defined as residual disease less than 2 cm), and therefore successful pregnancies (14 live births) after treatment. Women with carcinoma tended to have advanced disease at time of diagnosis (63% FIGO Stage III and IV), and consequently fewer women were candidates for fertility-sparing surgery (13%), with only one woman having two live births after treatment. In this study, age younger than 40 years alone was not associated with a better prognosis.
Hu et al. published the results of their multi-centre retrospective study on women aged 40 years or younger with epithelial ovarian cancer. They studied 94 women who received fertility-sparing surgery with a median follow up of 58.7 months. Fertility-sparing surgery was defined as conservation of one ovary and the uterus after staging procedures, which included removal of the affected ovary, peritoneal washings, omentectomy, pelvic and para-aortic lymphadenectomy. The median age in the study group was 28 years. Only 11 out of 94 women had FIGO Stage III disease and only one woman had a high-grade histology. The study population can therefore be characterised as young, with a diagnosis of early stage, low-grade epithelial ovarian cancer. A total of 17 pregnancies with seven live births took place, with most of these resulting from spontaneous conception. The elective abortion rate in this report was almost 30% (five out of 17 electing termination). Almost 90% of these women, however, resumed normal menstrual periods and by extension their reproductive potential. Chemotherapy did not affect reproductive potential in these young women.
Conservative surgery did not adversely affect survival, which was found to be comparable to other studies unrestricted by age. Survival was ultimately a function of disease stage, tumour grade and histology, and not necessarily of age.
Common clinical presentations of epithelial ovarian cancer in reproductive age women
Young women with epithelial ovarian cancer most commonly present with abdominal distention and pain. Complaints of an increase in abdominal girth resulting in the discovery of a pelvic mass is also a common presentation. Although less common, complaints of dyspareunia should also be investigated for a pelvic mass.
It is important to remember that even young women can present with advanced epithelial ovarian cancer and that the symptoms described above are often associated with the constellation of symptoms in the premenstrual phase. It is therefore prudent to maintain a low index of suspicion for any woman presenting with these symptoms.
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
