Contemporary primary treatment of women with stage II-IV low-grade serous ovarian/peritoneal cancer (LGSOC): Determinants of relapse and disease-free survival

Published:September 19, 2022DOI:


      • Following contemporary primary therapy, 98% of women with stage II-IV LGSOC who relapsed did so within 5 years of diagnosis.
      • Fifty-one percent of women who received contemporary primary therapy had not relapsed at time of analysis.
      • This study delineates several clinicopathologic factors that may be associated with patient outcomes.



      The purpose of the present study is to describe a cohort who received contemporary primary treatment for stage II-IV low-grade serous ovarian/peritoneal cancer (LGSOC), including patient characteristics and determinants of relapse and disease-free survival.


      The study included 99 patients: 1) with pathologically confirmed stage II-IV LGSOC of the ovary or peritoneum, 2) who underwent primary treatment consisting of cytoreductive surgery and either a) platinum/taxane chemotherapy followed by aromatase inhibitor maintenance therapy or b) aromatase inhibitor monotherapy, and 3) for whom there was availability of clinical data. Descriptive statistics were used to characterize clinicodemographic features. Subgroups were compared for PFS and OS. Multivariable Cox regression analyses were performed.


      Median PFS for the entire cohort was 56.8 months (95% CI, 41.3-NE), and median OS was 130.7 months (95% CI, 115.0–146.4). Forty-nine of 99 (49.5%) patients have relapsed to date. For these 49 patients, median time from diagnosis to relapse was 29.6 months (95% CI, 24.6–33.1) (range, 5.4–69.1 months). Only 1/49 (2%) patients who relapsed did so >5 years from diagnosis. Fifty (50.0%) patients have not experienced disease progression or relapse. Median follow-up time for these 50 patients is 86.2 months (range, 25.3–169.0). Thirty-three of the 50 (66.0%) have been followed for >5 years from diagnosis. On regression analyses, factors associated with improved patient outcomes—either PFS, OS, or both–included no gross residual disease, normal serum CA 125 at diagnosis, primary peritoneal site, and presence of extensive psammomatous calcifications.


      This is the first report to describe the clinicopathologic features and outcomes of women with stage II-IV LGSOC who received contemporary primary therapy.


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        • Malpica A.
        • Deavers M.T.
        • Lu K.
        • Bodurka D.C.
        • Atkinson E.N.
        • Gershenson D.M.
        • Silva E.G.
        Grading ovarian serous carcinoma using a two-tier system.
        Am. J. Surg. Pathol. 2004; 28: 496-504
        • Gershenson D.M.
        • Sun C.C.
        • Lu K.H.
        • Coleman R.L.
        • Sood A.K.
        • Malpica A.
        • Deavers M.T.
        • Silva E.G.
        • Bodurka D.C.
        Clinical behavior of stage II-IV low-grade serous carcinoma of the ovary.
        Obstet. Gynecol. 2006; 108: 361-368
        • Gershenson D.M.
        • Sun C.C.
        • Bodurka D.C.
        • et al.
        Recurrent low-grade serous ovarian carcinoma is relatively chemoresistant.
        Gynecol. Oncol. 2009; 114: 48-52
        • Gershenson D.M.
        • Bodurka D.C.
        • Lu K.H.
        • 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: 2675-2682
        • Grabowski J.P.
        • 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: 457-462
        • Cobb L.P.
        • Sun C.C.
        • Iyer R.
        • et al.
        The role of neoadjuvant chemotherapy in the management of low-grade serous carcinoma of the ovary and peritoneum: further evidence of relative chemoresistance.
        Gynecol. Oncol. 2020; 158: 653-658
        • Slomovitz B.
        • Gourley C.
        • Carey M.S.
        • et al.
        Low-grade serous ovarian cancer: state of the science.
        Gynecol. Oncol. 2020; 156: 715-725
        • Scott S.A.
        • Fernandez M.L.
        • Kim H.
        • et al.
        Low-grade serous carcinoma (LGSC): a Canadian multicenter review of practice patterns and patient outcomes.
        Gynecol. Oncol. 2020; 157: 36-45
        • Gershenson D.M.
        • Sun C.C.
        • Iyer R.B.
        • Malpica A.L.
        • Kavanagh J.J.
        • Bodurka D.C.
        • Schmeler K.
        • Deavers M.
        Hormonal therapy for recurrent low-grade serous carcinoma of the ovary or peritoneum.
        Gynecol. Oncol. 2012; 125: 661-666
        • Buttarelli M.
        • Mascilini F.
        • Zannoni G.F.
        • et al.
        Hormone receptor expression profile of low-grade serous ovarian cancers.
        Gynecol. Oncol. 2017; 145: 352-360
        • Llaurado Fernandez M.
        • Dawson A.
        • Kim H.
        • et al.
        Hormone receptor expression and outcomes in low-grade serous ovarian carcinoma.
        Gynecol. Oncol. 2020; 157: 12-20
        • Cheasley D.
        • Nigam A.
        • Zethoven M.
        • et al.
        Genomic analysis of low-grade serous ovarian carcinoma to identify key drivers and therapeutic vulnerabilities.
        J. Pathol. 2021; 253: 41-54
        • Gershenson D.M.
        • Sun C.C.
        • Westin S.N.
        • et al.
        The genomic landscape of low-grade serous ovarian/peritoneal carcinoma and its impact on clinical outcomes.
        Gynecol. Oncol. 2022; 165: 560-567
        • Gershenson D.M.
        • Bodurka D.C.
        • Coleman R.L.
        • Lu K.H.
        • Malpica A.
        • Sun C.C.
        Hormonal maintenance therapy for women with low-grade serous Cancer of the ovary or peritoneum.
        J. Clin. Oncol. 2017; 35: 1103-1111
        • Fader A.N.
        • Bergstrom J.
        • Jernigan A.
        • et al.
        Primary cytoreductive surgery and adjuvant hormonal monotherapy in women with advanced low-grade serous ovarian carcinoma: reducing overtreatment without compromising survival?.
        Gynecol. Oncol. 2017; 147: 85-91
        • National Comprehensive Cancer Network
        NCCN Clinical Practice Guidelines in Oncology: Ovarian Cancer Including Fallopian tube Cancer and Primary Peritoneal Cancer. Version 1.2022-January 18, 2022.
        Date: 2022
        • Gershenson D.M.
        • Cobb L.P.
        • Sun C.C.
        Clinical commentary. Endocrine therapy in the management of low-grade serous ovarian/peritoneal carcinoma: mounting evidence for the relative efficacy of tamoxifen and aromatase inhibitors.
        Gynecol. Oncol. 2020; 159: 601-603
        • Harris P.A.
        • et al.
        Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support.
        J. Biomed. Inform. 2009; 42: 377-381
        • Kaplan E.L.
        • Meier P.
        Nonparametric estimation from incomplete observations.
        J. Am. Stat. Assoc. 1958; 53: 457-481
        • Schemper M.
        • Smith T.L.
        A note on quantifying follow-up in studies of failure time.
        Control. Clin. Trials. 1996; 17: 343-346
        • Ali R.H.
        • Kalloger S.E.
        • Santos J.L.
        • et al.
        Stage II to IV low-grade serous carcinoma of the ovary is associated with a poor prognosis: a clinicopathologic study of 32 patients from a population-based tumor registry.
        Int. J. Gynecol. Pathol. 2013; 32: 529-535
        • Nickles Fader A.
        • Java J.
        • Ueda S.
        • et al.
        Survival in women with grade 1 serous ovarian carcinoma.
        Obstet. Gynecol. 2013; 122: 225-232
        • Fader A.
        • Java J.
        • Krivak T.C.
        • 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: 560-565
        • Ahn G.
        • Folkins A.K.
        • McKenney J.K.
        • Longacre T.A.
        Low-grade serous carcinoma of the ovary: Clinicopathologic analysis of 52 invasive cases and identification of a possible noninvasive intermediate lesion.
        Am. J. Surg. Pathol. 2016; 40: 1165-1176
        • Gockley A.
        • Melamed A.
        • Bregar A.J.
        • et al.
        Outcomes of women with high-grade and low-grade advanced-stage serous epithelial ovarian cancer.
        Obstet. Gynecol. 2017; 129: 439-447
        • Tang M.
        • O’Connell R.L.
        • Amant F.
        • et al.
        PARAGON: a phase II study of anastrozole in patients with estrogen receptor-positive recurrent/metastatic low-grade ovarian cancers and serous borderline tumors.
        Gynecol. Oncol. 2019; 154: 531-538
        • Gershenson D.M.
        • Miller A.
        • Brady W.E.
        • et al.
        Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomized, open-label, multicentre, phase 2/3 trial.
        Lancet. 2022; 399: 541-553
        • Kang J.-H.
        • Lai Y.-L.
        • Cheng W.-F.
        • et al.
        Clinical factors associated with prognosis in low-grade serous ovarian carcinoma: experiences at two large academic institutions in Korea and Taiwan.
        Sci. Rep. 2020; 10: 20012
        • Gilks C.B.
        • Bell D.A.
        • Scully R.E.
        Serous psammocarcinoma of the ovary and peritoneum.
        Int. J. Gynecol. Pathol. 1990; 9: 110-121
        • Delhorme J.-B.
        • Ohayon J.
        • Gouy S.
        • et al.
        Ovarian and peritoneal psammocarcinoma: results of a multicenter study on 25 patients.
        Eur. J. Surg. Oncol. 2020; 46: 862-867
        • Rettenmaier M.A.
        • Goldstein B.H.
        • Epstein H.D.
        • et al.
        Serous psammocarcinoma of the ovary: an unusual finding.
        Gynecol. Oncol. 2005; 99: 510-511
        • Vimplis S.
        • Williamson K.M.
        • Chaudry Z.
        • Nuuns D.
        Psammocarcinoma of the ovary: a case report and review of the literature.
        Gynecol. Surg. 2006; 3: 55-57

      Linked Article

      • Low grade serous ovarian cancer: Unpicking drivers of outcome
        Gynecologic OncologyVol. 167Issue 2
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          Low grade serous ovarian cancer (LGSOC) was first recognised as a separate entity almost two decades ago. In the first ten years since then, the number of dedicated LGSOC studies was low, reporting data from only a small number of specialist institutions. However, over the last 5 years there has been a wider, more concerted research effort that has driven substantial progress in uncovering the biological and clinical nuances of this unique disease type. This has included retrospective studies demonstrating the value of endocrine therapy [1,2] which have informed clinical guidelines and first-line trial design [3], randomised phase III trials demonstrating the value of MEK inhibitors in the relapsed disease setting [4,5] and most recently, a number of investigations that have painted a more detailed picture of the molecular landscape in LGSOC [6–9].
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