Fertility-sparing surgery in young women with ovarian cancer and borderline ovarian tumors

Abstract: Background: Based on the cell origin of the tumor, ovarian cancer (OC) is divided in epithelial ovarian cancer (EOC), including borderline ovarian tumors (BOT), and nonepithelial ovarian cancer (NEOC), which includes sex cord stromal tumors and malignant ovarian germ cell tumors. Each subgroup contains several histological subtypes of varying malignant potential and prognosis. Although the majority of ovarian tumors are diagnosed in postmenopausal women, these can also be found in women of reproductive age. The standard treatment of ovarian tumors encompasses extensive surgery including hysterectomy and bilateral salpingo-oophorectomy, which will result in infertility in women of reproductive age. Preservation of fertility is currently regarded as one of the most important issues related to health-related quality of life (HRQoL) in young cancer patients. Fertility-sparing surgery (FSS), defined as the preservation of the uterus and at least part of one ovary, may be an option for fertility preservation in women with OC and BOTs. In current practice, FSS can be considered in selected women of childbearing age, who wish to preserve their future fertility, whenever conditions indicating no increased risk regarding prognosis are met. Aim: The overall aim of this thesis was to explore the safety and the reproductive outcomes of FSS for treatment of early stage OC and BOTs in young women of reproductive age and to assess the impact of these diseases in women’s HRQoL, sexual and psychological health. Methods: A nationwide prospective population-based cohort study was conducted, including all women 18-40 years old with a confirmed diagnose of stage I NEOC (study I), EOC (study II), or BOTs (study III), registered in the Swedish quality register for gynecological cancer (SQRGC) between 2008-2015. Detailed data on surgery, staging, pathology reports and follow-up were extracted from the register and used when assessing the safety in terms of overall survival (OS), disease-free survival (DFS) and recurrence-rate. Women undergoing FSS were compared with women undergoing radical surgery (RS). To assess the efficacy of FSS, the proportion of women given birth after undergoing FSS and the proportion receiving treatment for infertility using assisted reproductive technologies (ART) were obtained by crosslinking individuals to the Swedish medical birth register and the National quality register for assisted reproduction. With the aim to explore how ovarian tumors diagnosed in young women of reproductive age would affect self-reported HRQoL and sexual and psychological health, a multicenter longitudinal cohort study was conducted (study IV). Women 18-40 years old undergoing FSS at one of the seven university hospitals in Sweden, between 2016-2018 were invited to participate in the study. Clinical data were prospectively collected including data regarding diagnosis, surgery and histopathological findings, as well as oncological and reproductive outcomes, every sixth month during follow-up. The study participants were asked to answer a questionnaire consisting of EORTC QLQ-C30, EORTC QLQ-OV28, FSFI, HADS and a study specific questionnaire regarding reproductive concerns, before surgery and at one- and two-years follow-up. Results: A total of 433 women were included in the nationwide population-based cohort. Out of these 73 women were diagnosed with NEOC (study I), 83 women with EOC (study II) and 277 were diagnosed with BOTs (study III). The proportion of women undergoing FSS in each cohort were 78% (study I), 43% (study II), and 77% (study III), respectively. The 5- year OS according to tumor type were 98% in NEOC, 92% in EOC and 99% in BOTs, with no statistical differences in OS between women undergoing FSS and RS. There was not any significant difference in DFS between women undergoing FSS compared to women undergoing RS for stage I NEOC or EOC. Prognostic factors associated with an increasing risk of recurrence in EOC were stage IC2 tumors and histologic subtypes of high malignant potential, which were more often seen in women undergoing RS. Natural fertility was maintained after FSS in all three cohorts, and only a minor proportion had undergone ARTtreatment. A strong desire for biological children, that persisted overtime, was reported by the 49 women included in study IV. HRQoL, sexual and psychological health improved overtime and there was a significant decrease in the proportion of women with sexual dysfunction. Having a child was associated with a higher score of sexual health. Conclusion: The OS for stage I NEOC, EOC and BOTs was excellent and not affected by the use of FSS. The feasibility of FSS in stage IC2/3 and high-grade EOC, remains unsolved due to the low number of cases with those risk factors undergoing FSS. Further research is needed, adding cases to the literature. Until then, decisions regarding FSS in high-risk tumors must be taken into consideration at a multidisciplinary team conference discussing treatment options and recommendations together with the patient. Natural fertility is preserved by the use of FSS as treatment for stage I OC and BOTs. HRQoL, sexual- and psychological health improved overtime in women 18-40 years old undergoing FSS for OC and BOT.

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