Comparison of surgical and oncologic outcomes in patients with clear cell ovarian carcinoma associated with and without endometriosis

Purpose To compare clinical characteristics, surgical and oncologic outcomes of clear cell ovarian cancer among patients with cancer arising from endometriosis, cancer coexisting with endometriosis, and cancer without endometriosis.

A retrospective chart review of patients diagnosed with clear cell ovarian cancer during January 1998–March 2013 was performed. All histopathology specimens were reviewed by a gynecologic pathologist and classified into one of the three following endometriosis status groups: arising group, coexisting group, or without group. The primary outcome was disease-specific survival (DSS). The secondary outcomes were progression-free survival, surgical morbidities, response rate, recurrence rate, and cancer-specific death.

Finally, 249 patients were included. There were 82, 96, and 71 patients in the arising, coexisting, and without groups, respectively. Regarding baseline characteristics among groups, the without group was significantly older and had more advanced diseases. There was a significant difference in progression-free survival between the arising group and the without group (p = 0.003). Five-year progression-free survival rates were 62.8% in the arising group, 50.2% in the coexisting group, and 38.3% in the without group. DSS was not significantly different among groups. Multivariate analysis revealed ovarian surface invasion (HR = 2.76) and pelvic lymphadenectomy (HR = 0.39) to be independent prognostic factors for progression-free survival, whereas no remission after primary treatment (HR = 8.03) and pelvic lymphadenectomy (HR = 0.21) were prognostic factors for DSS. Intraoperative blood loss and residual tumor were significantly higher in the without group.

Endometriosis status was found not to significantly influence surgical and oncologic outcomes in patients with clear cell ovarian cancer. Similar content being viewed by others

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424 Wilailak S, Lertchaipattanakul N (2016) The epidemiologic status of gynecologic cancer in Thailand. J Gynecol Oncol 27(6):e65 Coburn SB, Bray F, Sherman ME, Trabert B (2017) International patterns and trends in ovarian cancer incidence, overall and by histologic subtype. Int J Cancer 140(11):2451–2460 del Carmen MG, Birrer M, Schorge JO (2012) Clear cell carcinoma of the ovary: a review of the literature. Gynecol Oncol 126(3):481–490 Chan JK, Teoh D, Hu JM, Shin JY, Osann K, Kapp DS (2008) Do clear cell ovarian carcinomas have poorer prognosis compared to other epithelial cell types? A study of 1411 clear cell ovarian cancers. Gynecol Oncol 109(3):370–376 Davis M, Rauh-Hain JA, Andrade C, Boruta DM 2nd, Schorge JO, Horowitz NS et al (2014) Comparison of clinical outcomes of patients with clear cell and endometrioid ovarian cancer associated with endometriosis to papillary serous carcinoma of the ovary. Gynecol Oncol 132(3):760–766 Ye S, Yang J, You Y, Cao D, Bai H, Lang J et al (2014) Comparative study of ovarian clear cell carcinoma with and without endometriosis in People’s Republic of China. Fertil Steril 102(6):1656–1662 Scarfone G, Bergamini A, Noli S, Villa A, Cipriani S, Taccagni G et al (2014) Characteristics of clear cell ovarian cancer arising from endometriosis: a two center cohort study. Gynecol Oncol 133(3):480–484 Yoshikawa H, Jimbo H, Okada S, Matsumoto K, Onda T, Yasugi T et al (2000) Prevalence of endometriosis in ovarian cancer. Gynecol Obstet Invest 50:11–17 (Suppl 1) Liu H, Xu Y, Ji J, Dong R, Qiu H, Dai X (2020) Prognosis of ovarian clear cell cancer compared with other epithelial cancer types: a population-based analysis. Oncol Lett 19(3):1947–1957 Ye S, Yang J, You Y, Cao D, Huang H, Wu M et al (2015) Comparison of clinical characteristic and prognosis between ovarian clear cell carcinoma and serous carcinoma: a 10-year cohort study of Chinese patients. PLoS ONE 10(7):e0133498 Ku FC, Wu RC, Yang LY, Tang YH, Chang WY, Yang JE et al (2018) Clear cell carcinomas of the ovary have poorer outcomes compared with serous carcinomas: results from a single-center Taiwanese study. J Formos Med Assoc 117(2):117–125 Matsuzaki S, Yoshino K, Ueda Y, Matsuzaki S, Kakuda M, Okazawa A et al (2015) Potential targets for ovarian clear cell carcinoma: a review of updates and future perspectives. Cancer Cell Int 15:117 Sugiyama T, Kamura T, Kigawa J, Terakawa N, Kikuchi Y, Kita T et al (2000) Clinical characteristics of clear cell carcinoma of the ovary: a distinct histologic type with poor prognosis and resistance to platinum-based chemotherapy. Cancer 88(11):2584–2589 Nezhat FR, Pejovic T, Reis FM, Guo SW (2014) The link between endometriosis and ovarian cancer: clinical implications. Int J Gynecol Cancer 24(4):623–628 Son B, Lee S, Youn H, Kim E, Kim W, Youn B (2017) The role of tumor microenvironment in therapeutic resistance. Oncotarget 8(3):3933–3945 Melamed A, Manning-Geist B, Bregar AJ, Diver EJ, Goodman A, Del Carmen MG et al (2017) Associations between residual disease and survival in epithelial ovarian cancer by histologic type. Gynecol Oncol 147(2):250–256 Orezzoli JP, Russell AH, Oliva E, Del Carmen MG, Eichhorn J, Fuller AF (2008) Prognostic implication of endometriosis in clear cell carcinoma of the ovary. Gynecol Oncol 110(3):336–344 Park JY, Kim DY, Suh DS, Kim JH, Kim YM, Kim YT et al (2018) Significance of ovarian endometriosis on the prognosis of ovarian clear cell carcinoma. Int J Gynecol Cancer 28(1):11–18 Zhao T, Shao Y, Liu Y, Wang X, Guan L, Lu Y (2018) Endometriosis does not confer improved prognosis in ovarian clear cell carcinoma: a retrospective study at a single institute. J Ovarian Res 11(1):53 Sampson JA (1925) Endometrial carcinoma of ovary arising in endometrial tissue in that organ. Arch Surg 10:1–72 Scott RB (1953) Malignant changes in endometriosis. Obstet Gynecol 2(3):283–289 Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247 Bulun SE, Wan Y, Matei D (2019) Epithelial mutations in endometriosis: link to ovarian cancer. Endocrinology 160(3):626–638 Wilbur MA, Shih IM, Segars JH, Fader AN (2017) Cancer implications for patients with endometriosis. Semin Reprod Med 35(1):110–116 Pearce CL, Templeman C, Rossing MA, Lee A, Near AM, Webb PM et al (2012) Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies. Lancet Oncol 13(4):385–394 Wiegand KC, Shah SP, Al-Agha OM, Zhao Y, Tse K, Zeng T et al (2010) ARID1A mutations in endometriosis-associated ovarian carcinomas. N Engl J Med 363(16):1532–1543 Chandler RL, Damrauer JS, Raab JR, Schisler JC, Wilkerson MD, Didion JP et al (2015) Coexistent ARID1A-PIK3CA mutations promote ovarian clear-cell tumorigenesis through pro-tumorigenic inflammatory cytokine signalling. Nat Commun 6:6118 Sato N, Tsunoda H, Nishida M, Morishita Y, Takimoto Y, Kubo T et al (2000) Loss of heterozygosity on 10q23.3 and mutation of the tumor suppressor gene PTEN in benign endometrial cyst of the ovary: possible sequence progression from benign endometrial cyst to endometrioid carcinoma and clear cell carcinoma of the ovary. Cancer Res 60(24):7052–7056

The authors gratefully acknowledge Mr. Suthipol Udompunthurak of the Division of Clinical Epidemiology, Department of Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand for assistance with statistical analysis. Funding This was an unfunded study. Author information Authors and Affiliations Contributions RC: conceptualization, methodology, data collection, and writing (original draft); SH: pathological review and writing (review and editing); MB: writing (review and editing); ST: writing (review and editing); AJ: writing (review and editing); PC: writing (review and editing); PS: writing (review and editing); and, NJ: conceptualization, methodology, statistical analysis, and writing (original draft, review and editing). Corresponding author Ethics declarations Conflict of interest All authors declare no personal or professional conflicts of interest, and no financial support from the companies that produce and/or distribute the drugs, devices, or materials described in this report. Ethical approval The study protocol was approved by the Siriraj Institutional Review Board (SIRB) of the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand in March 2018 (Number Si147/2018). Informed consent Consent statement is not applicable for this retrospective study. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information Below is the link to the electronic supplementary material. Rights and permissions About this article Cite this article Charatsingha, R., Hanamornroongruang, S., Benjapibal, M. et al. Comparison of surgical and oncologic outcomes in patients with clear cell ovarian carcinoma associated with and without endometriosis. Arch Gynecol Obstet 304, 1569–1576 (2021). https://doi.org/10.1007/s00404-021-06096-6 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s00404-021-06096-6