An evaluation of progression free survival and overall survival of ovarian cancer patients with clear cell carcinoma versus serous carcinoma treated with platinum therapy: An NRG Oncology/Gynecologic Oncology Group experience

Published:August 11, 2017DOI:


      • In early stage patients, PFS was better for OCCC than for SOC.
      • In late-stage patients, OCCC was significantly associated with decreased OS.
      • Treatment effect was influenced by histology.



      We examined disparities in prognosis between patients with ovarian clear cell carcinoma (OCCC) and serous epithelial ovarian cancer (SOC).


      We reviewed data from FIGO stage I–IV epithelial ovarian cancer patients who participated in 12 prospective randomized GOG protocols. Proportional hazards models were used to compare progression-free survival (PFS) and overall survival (OS) by cell type (clear cell versus serous).


      There were 10,803 patients enrolled, 9531 were eligible, evaluable and treated with platinum, of whom 544 (6%) had OCCC, 7054 (74%) had SOC, and 1933 (20%) had other histologies and are not included further. In early stage (I–II) patients, PFS was significantly better in OCCC than in SOC patients. For late stage (III, IV) patients, OCCC had worse PFS and OS compared to SOC, OS HR = 1.66 (1.43, 1.91; p < 0.001). After adjusting for age and stratifying by protocol and treatment arm, stage, performance status, and race, OCCC had a significantly decreased OS, HR = 1.53 (1.33, 1.76; p < 0.001). In early stage cases, there was a significantly decreased treatment effect on PFS for consolidative therapy with weekly Paclitaxel versus observation in OCCC compared to SOC (p = 0.048).


      This is one of the largest analyses to date of OCCC treated on multiple cooperative group trials. OCCC histology is more common than SOC in early stage disease. When adjusted for prognostic factors, in early stage patients, PFS was better for OCCC than for SOC; however, in late-stage patients, OCCC was significantly associated with decreased OS. Finally, treatment effect was influenced by histology.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Gynecologic Oncology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Lee K.R.
        • Tavassolli F.A.
        • Prat J.
        • et al.
        Surface epithelial stromal tumors.
        in: Tavassoli F.A. Devilee P. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. IARC Press, Lyon2003: 117-145
        • Kobel M.
        • Kalloger S.E.
        • Huntsman D.G.
        • et al.
        Differences in tumor type in low-stage versus high-stage ovarian carcinomas.
        Int. J. Gynecol. Pathol. 2010; 29: 203-211
        • Yahata T.
        • Banzai C.
        • Tanaka K.
        Histology-specific long-term trends in the incidence of ovarian cancer and borderline tumor in Japanese females: a population-based study from 1983 to 2007 in Niigata.
        J. Obstet. Gynaecol. Res. 2012; 38: 645-650
        • Vasey P.A.
        • Jayson G.C.
        • Gordon A.
        • et al.
        Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma.
        J. Natl. Cancer Inst. 2004; 96: 1682-1691
        • Sugiyama T.
        • Kamura T.
        • Kigawa J.
        • et al.
        Clinical characteristics of clear cell carcinoma of the ovary: a distinct histologic type with poor prognosis and resistance to platinum-based chemotherapy.
        Cancer. 2000; 88: 2584-2589
        • Chan J.K.
        • Teoh D.
        • Hu J.M.
        • et al.
        Do clear cell ovarian carcinomas have poorer prognosis compared to other epithelial cell types? A study of 1411 clear cell ovarian cancers.
        Gynecol. Oncol. 2008; 109: 370-376
        • Omura G.A.
        • Brady M.F.
        • Homesley H.D.
        • et al.
        Long-term follow-up and prognostic factor analysis in advanced ovarian carcinoma: the gynecologic oncology group experience.
        J. Clin. Oncol. 1991; 9: 1138-1150
        • Goff B.A.
        • Sainz de la Cuesta R.
        • Muntz H.G.
        • et al.
        Clear cell carcinoma of the ovary: a distinct histologic type with poor prognosis and resistance to platinum-based chemotherapy in stage III disease.
        Gynecol. Oncol. 1996; 60: 412-417
        • Winter III, W.E.
        • Maxwell G.L.
        • Tian C.
        • et al.
        Prognostic factors for stage III epithelial ovarian cancer: a Gynecologic Oncology Group Study.
        J. Clin. Oncol. 2007; 25: 3621-3627
        • Duska L.R.
        • Garrett L.
        • Henretta M.
        • et al.
        When ‘never-events’ occur despite adherence to clinical guidelines: the case of venous thromboembolism in clear cell cancer of the ovary compared with other epithelial histologic subtypes.
        Gynecol. Oncol. 2010; 116: 374-377
        • Bamias A.
        • Psaltopoulou T.
        • Sotiropoulou M.
        • et al.
        Mucinous but not clear cell histology is associated with inferior survival in patients with advanced stage ovarian carcinoma treated with platinum-paclitaxel chemotherapy.
        Cancer. 2010; 116: 1462-1468
        • Pectasides D.
        • Fountzilas G.
        • Aravantinos G.
        • et al.
        Advanced stage clear-cell epithelial ovarian cancer: the Hellenic Cooperative Oncology Group experience.
        Gynecol. Oncol. 2006; 102: 285-291
        • Sauerbrei W.
        • Royston P.
        • Look M.
        A new proposal for multivariable modelling of time-varying effects in survival data based on fractional polynomial time-transformation.
        Biom. J. 2007; 49: 453-473
        • Takano M.
        • Sugiyama T.
        • Yaegashi N.
        • et al.
        Less impact of adjuvant chemotherapy for stage I clear cell carcinoma of the ovary: a retrospective Japan Clear Cell Carcinoma Study.
        Int. J. Gynecol. Cancer. 2010; 20: 1506-1510
        • Al-Barrak J.
        • Santos J.L.
        • Tinker A.
        • et al.
        Exploring palliative treatment outcomes in women with advanced or recurrent ovarian clear cell carcinoma.
        Gynecol. Oncol. 2011; 122: 107-110
        • Yamaguchi K.
        • Mandai M.
        • Oura T.
        • et al.
        Identification of an ovarian clear cell carcinoma gene signature that reflects inherent disease biology and the carcinogenic processes.
        Oncogene. 2010; 29: 1741-1752
        • Stany M.P.
        • Vathipadiekal V.
        • Ozbun L.
        • et al.
        Identification of novel therapeutic targets in microdissected clear cell ovarian cancers.
        PLoS One. 2011; 6e21121
        • Bitler B.G.
        • Aird K.M.
        • Zhang R.
        Epigenetic synthetic lethality in ovarian clear cell carcinoma: EZH2 and ARID1A mutations.
        Mol. Cell. Oncol. 2016; 3e1032476
        • Rahman M.
        • Nakayama K.
        • Rahman M.T.
        • et al.
        Clinicopathologic and biological analysis of PIK3CA mutation in ovarian clear cell carcinoma.
        Hum. Pathol. 2012; 43: 2197-2206
        • Mabuchi S.
        • Kawase C.
        • Altomare D.A.
        • et al.
        Vascular endothelial growth factor is a promising therapeutic target for the treatment of clear cell carcinoma of the ovary.
        Mol. Cancer Ther. 2010; 9: 2411-2422
        • Han E.K.
        • Tahir S.K.
        • Cherian S.P.
        • et al.
        Modulation of paclitaxel resistance by annexin IV in human cancer cell lines.
        Br. J. Cancer. 2000; 83: 83-88
        • Choi C.H.
        • Sung C.O.
        • Kim H.J.
        • et al.
        Overexpression of annexin A4 is associated with chemoresistance in papillary serous adenocarcinoma of the ovary.
        Hum. Pathol. 2013; 44: 1017-1023
        • Schulz C.
        • Boeck S.
        • Heinemann V.
        • et al.
        UGT1A1 genotyping: a predictor of irinotecan-associated side effects and drug efficacy?.
        Anti-Cancer Drugs. 2009; 20: 867-879
        • Arakawa N.
        • Miyagi E.
        • Nomura A.
        • et al.
        Secretome-based identification of TFPI2, a novel serum biomarker for detection of ovarian clear cell adenocarcinoma.
        J. Proteome Res. 2013; 14: 4340-4350
        • Munksgaard P.
        • Blaakaer J.
        The association between endometriosis and ovarian cancer: a review of histological, genetic and molecular alterations.
        Gynecol. Oncol. 2012 Jan; 124: 164-169