Skip to main content
SpringerLink
Log in

Low-Grade Serous Ovarian Cancer: Current Treatment Paradigms and Future Directions

  • Gynecologic Cancers (LA Cantrell, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Low-grade serous ovarian cancer (LGSOC) is a rare subtype of ovarian cancer, accounting for approximately 10% of cases of serous ovarian cancer. Patients typically present at a younger age have a protracted clinical course with survival for those with recurrent disease nearing 10 years, and have a high prevalence of somatic (tumor-specific) mutations affecting the mitogen-activated protein kinase (MAPK) pathway. Initial treatment of patients with stage IC–IV disease is similar to that of high-grade serous ovarian cancer with surgery and platinum/taxane-based chemotherapy. Selected patients may benefit from hormonal maintenance therapy following chemotherapy, in particular those with evidence of residual disease at completion of therapy. In the recurrent setting, the highest response rates to chemotherapy have been noted in those patients receiving chemotherapy in combination with bevacizumab. While hormonal therapies may offer disease stabilization with relatively low toxicity, objective response rates remain low. The use of targeted therapies such as MEK inhibitors remains an active area of investigation and those patients with MAPK pathway alterations may derive the greatest benefit from these agents.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. •• Malpica A, et al. Grading ovarian serous carcinoma using a two-tier system. Am J Surg Pathol. 2004;28(4):496–504. Pivotal change in classification of serous ovarain cancers from a three-tiered system to a binary high/low-grade system.

    Article  Google Scholar 

  2. Seidman JD, Horkayne-Szakaly I, Haiba M, Boice CR, Kurman RJ, Ronnett BM. The histologic type and stage distribution of ovarian carcinomas of surface epithelial origin. Int J Gynecol Pathol. 2004;23(1):41–4.

    Article  Google Scholar 

  3. Plaxe SC. Epidemiology of low-grade serous ovarian cancer. Am J Obstet Gynecol. 2008;198(4):459.e1–8. discussion 459 e8–9

    Article  Google Scholar 

  4. Integrated genomic analyses of ovarian carcinoma. Nature, 2011. 474(7353): p. 609–15.

  5. Kaern J, Trope CG, Abeler VM. A retrospective study of 370 borderline tumors of the ovary treated at the Norwegian Radium Hospital from 1970 to 1982. A review of clinicopathologic features and treatment modalities. Cancer. 1993;71(5):1810–20.

    Article  CAS  Google Scholar 

  6. Kaldawy A, Segev Y, Lavie O, Auslender R, Sopik V, Narod SA. Low-grade serous ovarian cancer: a review. Gynecol Oncol. 2016;143(2):433–8.

    Article  Google Scholar 

  7. Nougaret S, Lakhman Y, Molinari N, Feier D, Scelzo C, Vargas HA, et al. CT features of ovarian tumors: defining key differences between serous borderline tumors and low-grade serous carcinomas. AJR Am J Roentgenol. 2018;210(4):918–26.

    Article  Google Scholar 

  8. Gershenson DM, Bodurka DC, Lu KH, Nathan LC, Milojevic L, Wong KK, et al. Impact of age and primary disease site on outcome in women with low-grade serous carcinoma of the ovary or peritoneum: results of a large single-institution registry of a rare tumor. J Clin Oncol. 2015;33(24):2675–82.

    Article  Google Scholar 

  9. Gershenson DM, Sun CC, Bodurka D, Coleman RL, Lu KH, Sood AK, et al. Recurrent low-grade serous ovarian carcinoma is relatively chemoresistant. Gynecol Oncol. 2009;114(1):48–52.

    Article  Google Scholar 

  10. Gershenson DM, Sun CC, Lu KH, Coleman RL, Sood AK, Malpica A, et al. Clinical behavior of stage II-IV low-grade serous carcinoma of the ovary. Obstet Gynecol. 2006;108(2):361–8.

    Article  Google Scholar 

  11. Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365(26):2473–83.

    Article  CAS  Google Scholar 

  12. FDA approves Genentech’s avastin (bevacizumab) plus chemotherapy as a treatment for women with advanced ovarian cancer following initial Surgery. Genentech. https://www.gene.com/media/press-releases/14729/2018-06-13/fda-approves-genentechs-avastin-bevacizu

  13. •• Gershenson DM, et al. Hormonal maintenance therapy for women with low-grade serous cancer of the ovary or peritoneum. J Clin Oncol. 2017;35(10):1103–11. Large study showing significant improvement in progression-free survival with the use of hormonal maintenance therapy following initial therapy of LGSOC.

    Article  Google Scholar 

  14. Malpica A, Wong KK. The molecular pathology of ovarian serous borderline tumors. Ann Oncol. 2016;27(Suppl 1):i16–9.

    Article  Google Scholar 

  15. Grisham, R.N., et al., BRAF mutation is associated with early stage disease and improved outcome in patients with low-grade serous ovarian cancer. Cancer, 2013;119(3):548–554

    Article  Google Scholar 

  16. Turashvili G, Grisham RN, Chiang S, DeLair DF, Park KJ, Soslow RA, et al. BRAF(V)(600E) mutations and immunohistochemical expression of VE1 protein in low-grade serous neoplasms of the ovary. Histopathology. 2018;73:438–43.

    Article  Google Scholar 

  17. Grisham RN. Low-grade serous carcinoma of the ovary. Oncology. 2016;30(7):650–2.

    PubMed  Google Scholar 

  18. Bodurka, D.C., et al., Reclassification of serous ovarian carcinoma by a 2-tier system: a Gynecologic Oncology Group Study. Cancer, 2011.

  19. Gershenson DM, Sun CC, Iyer RB, Malpica AL, Kavanagh JJ, Bodurka DC, et al. Hormonal therapy for recurrent low-grade serous carcinoma of the ovary or peritoneum. Gynecol Oncol. 2012;125(3):661–6.

    Article  CAS  Google Scholar 

  20. Grisham RN, Sylvester BE, Won H, McDermott G, DeLair D, Ramirez R, et al. Extreme outlier analysis identifies occult mitogen-activated protein kinase pathway mutations in patients with low-grade serous ovarian cancer. J Clin Oncol. 2015;33(34):4099–105.

    Article  CAS  Google Scholar 

  21. Singer G, Oldt R, Cohen Y, Wang BG, Sidransky D, Kurman RJ, et al. Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma. J Natl Cancer Inst. 2003;95(6):484–6.

    Article  CAS  Google Scholar 

  22. Wong KK, Tsang YTM, Deavers MT, Mok SC, Zu Z, Sun C, et al. BRAF mutation is rare in advanced-stage low-grade ovarian serous carcinomas. Am J Pathol. 2010;177(4):1611–7.

    Article  CAS  Google Scholar 

  23. Vereczkey I, Serester O, Dobos J, Gallai M, Szakács O, Szentirmay Z, et al. Molecular characterization of 103 ovarian serous and mucinous tumors. Pathol Oncol Res. 2011;17(3):551–9.

    Article  Google Scholar 

  24. •• Grisham RN, et al. BRAF mutation is associated with early stage disease and improved outcome in patients with low-grade serous ovarian cancer. Cancer. 2013;119(3):548–54. Initial study indicating that BRAF mutation is associated with improved prognosis in LGSOC.

    Article  Google Scholar 

  25. Mayr D, Hirschmann A, Löhrs U, Diebold J. KRAS and BRAF mutations in ovarian tumors: a comprehensive study of invasive carcinomas, borderline tumors and extraovarian implants. Gynecol Oncol. 2006;103(3):883–7.

    Article  CAS  Google Scholar 

  26. Xu Y, Bi R, Xiao Y, Tu X, Li M, Li A, et al. Low frequency of BRAF and KRAS mutations in Chinese patients with low-grade serous carcinoma of the ovary. Diagn Pathol. 2017;12(1):87.

  27. •• Farley J, et al. Selumetinib in women with recurrent low-grade serous carcinoma of the ovary or peritoneum: an open-label, single-arm, phase 2 study. Lancet Oncol. 2013;14(2):134–40. The first phase II prospective study of systemic MEK inhibitor therapy performed in LGSOC.

    Article  CAS  Google Scholar 

  28. Takekuma M, Wong KK, Coleman RL. A long-term surviving patient with recurrent low-grade serous ovarian carcinoma treated with the MEK1/2 inhibitor, selumetinib. Gynecol Oncol Res Pract. 2016;3:5.

    Article  Google Scholar 

  29. Grisham, R., Moore K.N., Gordon M.S., Harb W., Cody G.R., Halpenny D.F., Makker V., Aghajanian C., Phase Ib study of binimetinib with paclitaxel in patients with platinum-resistant ovarian cancer: final results, potential biomarkers, and extreme responders. Clin Cancer Res, 2018, clincanres.0494.2018.

  30. Grisham RN, Iyer G, Sala E, Zhou Q, Iasonos A, DeLair D, et al. Bevacizumab shows activity in patients with low-grade serous ovarian and primary peritoneal cancer. Int J Gynecol Cancer. 2014;24(6):1010–4.

    Article  Google Scholar 

  31. Dalton HJ, Fleming ND, Sun CC, Bhosale P, Schmeler KM, Gershenson DM. Activity of bevacizumab-containing regimens in recurrent low-grade serous ovarian or peritoneal cancer: a single institution experience. Gynecol Oncol. 2017;145(1):37–40.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Memorial Sloan Kettering Cancer Center, 300 East 66th Street, office 1305, New York, NY, 10065, USA

    Rachel N. Grisham MD & Gopa Iyer MD

  2. Weill Cornell Medical College, New York, NY, USA

    Rachel N. Grisham MD & Gopa Iyer MD

Authors
  1. Rachel N. Grisham MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gopa Iyer MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rachel N. Grisham MD.

Ethics declarations

Conflict of Interest

Rachel N. Grisham has received compensation from Clovis Oncology for service as a consultant. Gopa Iyer declares that he has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Gynecologic Cancers

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Grisham, R.N., Iyer, G. Low-Grade Serous Ovarian Cancer: Current Treatment Paradigms and Future Directions. Curr. Treat. Options in Oncol. 19, 54 (2018). https://doi.org/10.1007/s11864-018-0571-8

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11864-018-0571-8

Keywords

Search

Navigation