Ovarian tumors

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Ovarian tumor encompasses a heterogeneous group of lesions with different cell/site origins, pathological grades, and prognoses. Epithelial ovarian cancers (EOCs) account for 90% of all cases. They include borderline ovarian tumors (BOTs) in a 10-20 % of cases, and malignant ovarian tumors in the remaining percentages. Non-epithelial cancers can be further divided into germ cell tumors (3%), sex cord-stromal tumors (2%) and other rare types (Kurman et al, 2014). BOTs and non-epithelial cancers exhibit less aggressive behavior than malignant EOCs and their incidence peaks at a younger age. 

Stage at diagnosis varies considerably between different cancer types. High-grade EOCs are mostly diagnosed at advanced stages, while early diagnosis (stage I) is usually achieved in more than 50% of all other types. Standard primary management involves hysterectomy with bilateral salpingo-oophorectomy, plus peritoneal and lymph node staging. It often includes adjuvant therapy for high-risk presentations (Berek et al, 2021).  

Fertility-sparing surgery aims to preserve the uterus and at least part of one ovary, and may be considered in young patients hoping to conceive in the future (Donnez et al, 2003; Morice et al, 2006). However, it is only advisable in a minority of cancer presentations diagnosed at a very early stage and with favorable prognostic factors, namely an acceptable risk of recurrence that would not impact patient survival (Johansen et al, 2019; 2020; 2021). There is no consensus on the surgical approach to the ovaries for each histotype (cystectomy versus oophorectomy). 

References:

  1. Kurman RJ, et al. WHO Classification of Tumours of Female Reproductive Organs. In WHO Classification of Tumours. 2014. Lyon:WHO Press.
  2. Berek JS, Renz M, Kehoe S, Kumar L, Friedlander M. Cancer of the ovary, fallopian tube, and peritoneum: 2021 update. Int J Gynaecol Obstet. 2021 Oct;155 Suppl 1:61-85. 
  3. Donnez J, Munschke A, Berliere M, Pirard C, Jadoul P, Smets M, Squifflet J.Safety of conservative management and fertility outcome in women with borderline tumors of the ovary. Fertil Steril 2003;79:1216–1221.
  4. Morice P. Borderline tumours of the ovary and fertility. Eur J Cancer 2006;42:149–158.
  5. Johansen G, Dahm-Kähler P, Staf C, Flöter Rådestad A, Rodriguez-Wallberg KA. Fertility-sparing surgery for treatment of non-epithelial ovarian cancer: Oncological and reproductive outcomes in a prospective nationwide population-based cohort study. Gynecol Oncol. 2019 Nov;155(2):287-293.
  6. Johansen G, Dahm-Kähler P, Staf C, Flöter Rådestad A, Rodriguez-Wallberg KA. A Swedish Nationwide prospective study of oncological and reproductive outcome following fertility-sparing surgery for treatment of early stage epithelial ovarian cancer in young women. BMC Cancer. 2020 Oct 19;20(1):1009. 
  7. Johansen G, Dahm-Kähler P, Staf C, Flöter Rådestad A, Rodriguez-Wallberg KA. Reproductive and obstetrical outcomes with the overall survival of fertile-age women treated with fertility-sparing surgery for borderline ovarian tumors in Sweden: a prospective nationwide population-based study. Fertil Steril. 2021 Jan;115(1):157-163.

Borderline ovarian tumors

In BOTS, fertility-sparing surgery often involves cystectomy, since there is bilateral occurrence in un to 40% of cases. This appears to yield increased intraovarian recurrence rates, however, without changing the long-term prognosis for patients (Canlorbe et al, 2021). Repeated surgery for disease recurrence may be detrimental of the remaining ovarian reserve and lead to subsequent infertility. For this reason, ovarian cortical strips are often retrieved and frozen at the time of first surgery for BOT in young women, accounting for around 20% of cases of ovarian tissue cryopreservation (Jadoul et al, 2017). 

The risk of reimplanting occult malignant cells with ovarian tissue transplantation been assessed in for patients with BOTs. Minimal residual disease was investigated in frozen-thawed ovarian tissue from 11 subjects diagnosed BOTS by immunohistochemistry, quantitative reverse transcription polymerase chain reaction and long-term xenografting to immunodeficient mice using specific molecular markers (cytokeratin 7 and mucin 1). These evaluations revealed BOT cells able to survive after transplantation in the cryopreserved ovarian tissue of 1 of 11 patients (9.1% of cases), proving the need of preimplantation analyses for patients who had their ovarian tissue cryopreserved for this reason (Masciangelo et al, 2017). 

References: 

  1. Canlorbe G, Chabbert-Buffet N, Uzan C. Fertility-Sparing Surgery for Ovarian Cancer. J Clin Med. 2021 Sep 18;10(18):4235. 
  2. Jadoul P, Guilmain A, Squifflet J, Luyckx M, Votino R, Wyns C, Dolmans MM. Efficacy of ovarian tissue cryopreservation for fertility preservation: lessons learned from 545 cases. Hum Reprod. 2017 May 1;32(5):1046-1054. 
  3. Masciangelo R, Bosisio C, Donnez J, Amorim CA, Dolmans MM. Safety of ovarian tissue transplantation in patients with borderline ovarian tumors. Hum Reprod. 2018 Feb 1;33(2):212-219.

Ovarian cancers

Conservative treatment of the ovaries in high-grade EOCs may increase the risk of disease recurrence. However, the increased recurrence of both intra-and extraovarian metastases may depend on the presence of poor prognostic factors associated with specific histotype than on fertility-sparing surgery (Bentivegna et al, 2016). 

In case of increased risk of premature ovarian insufficiency due to the need of adjuvant chemotherapy, a broader fertility preservation approach can be considered in addition to fertility sparing-surgery, with the aim of protecting the ovarian reserve. 

Vaginal oocyte retrieval after controlled ovarian stimulation (oocyte cryopreservation) is not advisable in the presence of the lesion, since it may be associated with issues like the risk of dissemination of tumor cells to the pelvic cavity and vaginal wall due to follicle puncture (Ohara et al, 2021). Oocyte retrieval from antral follicles may be performed ex vivo at the same time as surgery, but its success depends on the number of available antral follicles and oocyte maturation rates.  

Removal of tissue for ovarian tissue cryopreservation can be performed at the time of surgery, but further ovarian tissue transplantation cannot be considered without a clear assessment of the risk of transplanting malignant cells back to the pelvis (Kristensen et al, 2017). 

References:

  1. Bentivegna E, Morice P, Uzan C, Gouy S. Fertility-sparing surgery in epithelial ovarian cancer. Future Oncol. 2016 Feb;12(3):389-98.
  2. Ohara T, Kuji S, Takenaga T, Imai H, Endo H, Kanamori R, et al. Current state of fertility preservation for adolescent and young adult patients with gynecological cancer. Int J Clin Oncol. 2022 Jan;27(1):25-34. 
  3. Kristensen SG, Giorgione V, Humaidan P, Alsbjerg B, Bjørn AB, Ernst E, Andersen CY. Fertility preservation and refreezing of transplanted ovarian tissue-a potential new way of managing patients with low risk of malignant cell recurrence. Fertil Steril. 2017 May;107(5):1206-1213.

 

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