Management of low-grade serous carcinomas of the ovary
- David M Gershenson, MD
David M Gershenson, MD
- J Taylor Wharton MD Distinguished Chair in Gynecologic Oncology
- Professor of Gynecologic Oncology
- The University of Texas MD Anderson Cancer Center
- Michael J Birrer, MD, PhD
Michael J Birrer, MD, PhD
- Professor of Medicine
- Harvard Medical School
- Section Editors
- Barbara Goff, MD
Barbara Goff, MD
- Section Editor — Gynecologic Oncology
- Professor of Gynecologic Oncology
- University of Washington
- Don S Dizon, MD, FACP
Don S Dizon, MD, FACP
- Section Editor – Gynecologic Oncology
- Clinical Co-Director, Gynecologic Oncology
- Founder and Director, The Oncology Sexual Health Clinic
- Massachusetts General Hospital Cancer Center
- Associate Professor of Medicine
- Harvard Medical School
Ovarian cancer is the second most common gynecologic malignancy and the most common cause of gynecologic cancer death in the United States. (See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Epidemiology and risk factors", section on 'Epidemiology'.)
The most common epithelial ovarian cancer histologic subtype is serous. Approximately 90 percent of serous carcinomas are high-grade, and 10 percent are low-grade. Low-grade serous carcinoma of the ovary or peritoneum appears to exist on a continuum with serous borderline tumors, which are likely precursor lesions, and has a distinct pathology, clinical behavior, and prognosis compared with high-grade serous carcinoma. Thus, a diagnosis of low-grade serous carcinoma may be made de novo or following an original diagnosis of serous borderline tumor.
The pathogenesis, clinical presentation, diagnosis, and treatment of low-grade serous carcinoma will be reviewed here. Aspects of the management of ovarian and peritoneal carcinomas (of higher grade) as well as borderline ovarian tumors are discussed elsewhere.
- Malpica A, Deavers MT, Lu K, et al. Grading ovarian serous carcinoma using a two-tier system. Am J Surg Pathol 2004; 28:496.
- Principles and Practice of Gynecologic Oncology, 7, Chi DS, Berchuck A, Dizon DS, Yashar CM (Eds), Lippincott Williams & Wilkins, 2017.
- Bonome T, Lee JY, Park DC, et al. Expression profiling of serous low malignant potential, low-grade, and high-grade tumors of the ovary. Cancer Res 2005; 65:10602.
- Kuo KT, Guan B, Feng Y, et al. Analysis of DNA copy number alterations in ovarian serous tumors identifies new molecular genetic changes in low-grade and high-grade carcinomas. Cancer Res 2009; 69:4036.
- Teneriello MG, Ebina M, Linnoila RI, et al. p53 and Ki-ras gene mutations in epithelial ovarian neoplasms. Cancer Res 1993; 53:3103.
- Anglesio MS, Arnold JM, George J, et al. Mutation of ERBB2 provides a novel alternative mechanism for the ubiquitous activation of RAS-MAPK in ovarian serous low malignant potential tumors. Mol Cancer Res 2008; 6:1678.
- Wong KK, Tsang YT, Deavers MT, et al. BRAF mutation is rare in advanced-stage low-grade ovarian serous carcinomas. Am J Pathol 2010; 177:1611.
- Grisham RN, Iyer G, Garg K, et al. BRAF mutation is associated with early stage disease and improved outcome in patients with low-grade serous ovarian cancer. Cancer 2013; 119:548.
- Tsang YT, Deavers MT, Sun CC, et al. KRAS (but not BRAF) mutations in ovarian serous borderline tumour are associated with recurrent low-grade serous carcinoma. J Pathol 2013; 231:449.
- Gershenson DM, Sun CC, Lu KH, et al. Clinical behavior of stage II-IV low-grade serous carcinoma of the ovary. Obstet Gynecol 2006; 108:361.
- Gershenson DM, Bodurka DC, Lu KH, 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; 33:2675.
- Shimizu Y, Kamoi S, Amada S, et al. Toward the development of a universal grading system for ovarian epithelial carcinoma: testing of a proposed system in a series of 461 patients with uniform treatment and follow-up. Cancer 1998; 82:893.
- Classification and staging of malignant tumours in the female pelvis. Acta Obstet Gynecol Scand 1971; 50:1.
- Bodurka DC, Deavers MT, Tian C, et al. Reclassification of serous ovarian carcinoma by a 2-tier system: a Gynecologic Oncology Group Study. Cancer 2012; 118:3087.
- WHO Classification of Tumours of Female Reproductive Organs, Kurman RJ, Carcangiu ML, Herrington CS, Young RH (Eds), IARC, Lyon 2014. p.18.
- Fader AN, Java J, Krivak TC, et al. The prognostic significance of pre- and post-treatment CA-125 in grade 1 serous ovarian carcinoma: a gynecologic Oncology Group study. Gynecol Oncol 2014; 132:560.
- Genetic/Familial High-Risk Assessment: Breast and Ovarian. https://www.nccn.org/professionals/physician_gls/f_guidelines.asp (Accessed on April 10, 2017).
- Norquist BM, Harrell MI, Brady MF, et al. Inherited Mutations in Women With Ovarian Carcinoma. JAMA Oncol 2016; 2:482.
- Fader AN, Java J, Ueda S, et al. Survival in women with grade 1 serous ovarian carcinoma. Obstet Gynecol 2013; 122:225.
- Grabowski JP, Harter P, Heitz F, et al. Operability and chemotherapy responsiveness in advanced low-grade serous ovarian cancer. An analysis of the AGO Study Group metadatabase. Gynecol Oncol 2016; 140:457.
- Plaxe SC. Epidemiology of low-grade serous ovarian cancer. Am J Obstet Gynecol 2008; 198:459.e1.
- NCCN Clinical Practice Guidelines in Oncology. Ovarian Cancer. Version 1.2016. www.nccn.org/patients (Accessed on April 10, 2017).
- Schmeler KM, Sun CC, Bodurka DC, et al. Neoadjuvant chemotherapy for low-grade serous carcinoma of the ovary or peritoneum. Gynecol Oncol 2008; 108:510.
- Schmeler KM, Sun CC, Malpica A, et al. Low-grade serous primary peritoneal carcinoma. Gynecol Oncol 2011; 121:482.
- Romero I, Sun CC, Wong KK, et al. Low-grade serous carcinoma: new concepts and emerging therapies. Gynecol Oncol 2013; 130:660.
- Gershenson DM, Bodurka DC, Coleman RL, et al. Hormonal Maintenance Therapy for Women With Low-Grade Serous Cancer of the Ovary or Peritoneum. J Clin Oncol 2017; 35:1103.
- Crane EK, Sun CC, Ramirez PT, et al. The role of secondary cytoreduction in low-grade serous ovarian cancer or peritoneal cancer. Gynecol Oncol 2015; 136:25.
- Gershenson DM, Sun CC, Bodurka D, et al. Recurrent low-grade serous ovarian carcinoma is relatively chemoresistant. Gynecol Oncol 2009; 114:48.
- Wong KK, Lu KH, Malpica A, et al. Significantly greater expression of ER, PR, and ECAD in advanced-stage low-grade ovarian serous carcinoma as revealed by immunohistochemical analysis. Int J Gynecol Pathol 2007; 26:404.
- Gershenson DM, Sun CC, Iyer RB, et al. Hormonal therapy for recurrent low-grade serous carcinoma of the ovary or peritoneum. Gynecol Oncol 2012; 125:661.
- Escobar J, Klimowicz AC, Dean M, et al. Quantification of ER/PR expression in ovarian low-grade serous carcinoma. Gynecol Oncol 2013; 128:371.
- Oza AM, Cook AD, Pfisterer J, et al. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol 2015; 16:928.
- Schmeler KM, Tao X, Sun CC, et al. Encouraging responses with bevacizumab in recurrent low-grade serous ovarian cancer. J Clin Oncol 2010; 28:e15503.
- Dalton HJ, Fleming ND, Sun CC, et al. Activity of bevacizumab-containing regimens in recurrent low-grade serous ovarian or peritoneal cancer: A single institution experience. Gynecol Oncol 2017; 145:37.
- Grisham RN, Iyer G, Sala E, et al. Bevacizumab shows activity in patients with low-grade serous ovarian and primary peritoneal cancer. Int J Gynecol Cancer 2014; 24:1010.
- Rose PG, Mahdi H, Jernigan A, Yang B. Activity of Bevacizumab in Patients With Low-Grade Serous Ovarian Carcinoma. Int J Gynecol Cancer 2016; 26:1048.
- Ferriss JS, Java JJ, Bookman MA, et al. Ascites predicts treatment benefit of bevacizumab in front-line therapy of advanced epithelial ovarian, fallopian tube and peritoneal cancers: an NRG Oncology/GOG study. Gynecol Oncol 2015; 139:17.
- Gershenson DM, Sun CC, Wong KK. Impact of mutational status on survival in low-grade serous carcinoma of the ovary or peritoneum. Br J Cancer 2015; 113:1254.
- Kaldawy A, Segev Y, Lavie O, et al. Low-grade serous ovarian cancer: A review. Gynecol Oncol 2016; 143:433.
- Farley J, Brady WE, Vathipadiekal V, 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; 14:134.
- www.clinicaltrials.gov (Accessed on April 10, 2017).
- CLINICAL PRESENTATION
- Preoperative management
- - Imaging
- - Tumor markers
- - Genetic testing for hereditary cancer syndromes
- - Adjuvant treatment
- Stage IA, IB, and IC
- Stage II to IV
- Those in whom primary resection is not feasible
- Recurrent or metastatic disease
- Is there a role for angiogenesis inhibitors?
- INVESTIGATIONAL APPROACHES
- SUMMARY AND RECOMMENDATIONS