Prognosis of high-grade endometrial cancer: a comparison of serous-type and clear cell type to grade 3 endometrioid-type

Objective: To evaluate prognosis of high-grade endometrial cancers, comparing serous (SC) and clear cell (CCC) types to grade 3 endometrioid carcinoma (ECG3). Methods: Among patients with endometrial cancer treated in two decades, medical records of patients with high-grade endometrial cancer were retrospectively investigated. Results: Of 447 endometrial cancers, 107 (24%) high-grade endometrial cancers were identified, with the increasing incidence in the last decade (28% vs 19%; p = 0.026). There were 24 SC, 14 CCC and 69 ECG3. Median age was 62, 68, and 61 years, respectively, with the CCC type showing an elder age than the ECG3 type (p = 0.012). The rates of patients with Stage IIIc-IV, lymph node assessment or complete resection at primary surgery, and post-operative chemotherapy were not significantly different; however, response rate to first-line chemotherapy in patients with measurable disease was lower in SC than ECG3 (3 / 11, 27% vs 14 / 19, 74%; p = 0.037), regardless of regimens. Five-year overall survival (OS) was 40%, 71%, and 71% respectively, and five-year progression-free survival (PFS) was 25%, 71%, and 61%, respectively, showing SC with worse prognosis than ECG3 on both OS (p = 0.026) and PFS (p = 0.0028). According to the multivariate analysis, an >= 70, Stage IIIc-IV and incomplete resection were independent prognostic factors on poor OS, whereas SC, Stage IIIc-IV and incomplete resection were on poor PFS. Conclusions: The increasing trend of high-grade endometrial cancer and different outcomes according to histological subtypes, especially poor PFS and chemotherapeutic response in SC, were suggested.

High-grade endometrial cancer; Endometrioid; Serous; Clear cell; Prognosis; Chemotherapy

[1] Creasman W.T., Odicino F., Maisonneuve P., Quinn M.A., Beller U., Benedet J.L. et al.: “Carcinoma of the corpus uteri. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer”. Int. J. Gynaecol. Obstet., 2006, 95, S105.

[2] Cirisano F.D. Jr., Robboy S.J., Dodge R.K., Bentley R.C., Krigman H.R., Synan I.S. et al.: “The outcome of Stage I-II clinically and surgically staged papillary serous and clear cell endometrial cancers when compared with endometrioid carcinoma”. Gynecol. Oncol., 2000, 77, 55.

[3] Alektiar K.M., McKee A., Lin O., Venkatraman E., Zelefsky M.J., McKee B. et al.: “Is there a difference in outcome between Stage I-II endometrial cancer of papillary serous/clear cell and endometrioid FIGO Grade 3 cancer?”. Int. J. Radiat. Oncol. Biol. Phys., 2002, 54, 79.

[4] Sakuragi N., Hareyama H., Todo Y., Yamada H., Yamamoto R., Fujino T. et al.: “Prognostic significance of serous and clear cell adenocarcinoma in surgically staged endometrial carcinoma”. Acta. Obstet. Gynecol. Scand., 2000, 79, 311.

[5] Halperin R., Zehavi S., Langer R., Hadas E., Bukovsky I., Schneider D.: “Uterine papillary serous carcinoma (pure and mixed type) compared with moderately and poorly differentiated endometrioid carcinoma. A clinicopathologic study”. Eur. J. Gynaecol. Oncol., 2002, 23, 300.

[6] McMeekin D.S., Filiaci V.L., Thigpen J.T., Gallion H.H., Fleming G.F., Rodgers W.H.; Gynecologic Oncology Group study.: “The relationship between histology and outcome in advanced and recurrent endometrial cancer patients participating in first-line chemotherapy trials: a gynecologic oncology group study”. Gynecol. Oncol., 2007, 106, 16.

[7] Soslow R.A., Bissonnette J.P., Wilton A., Ferguson S.E., Alektiar K.M., Duska L.R. et al.: “Clinicopathologic analysis of 187 highgrade endometrial carcinomas of different histologic subtypes: similar outcomes belie distinctive biologic differences”. Am. J. Surg. Pathol., 2007, 31, 979.

[8] Creasman W.T., Kohler M.F., Odicino F., Maisonneuve P., Boyle P.: “Prognosis of papillary serous, clear cell, and grade 3 Stage I carcinoma of the endometrium”. Gynecol. Oncol., 2004, 95, 593.

[9] Boruta D.M. 2nd, Gehrig P.A., Groben P.A., Bae-Jump V., Boggess J.F., Fowler W.C. Jr. et al.: “Uterine serous and grade 3 endometrioid carcinomas: is there a survival difference?”. Cancer, 2004, 101, 2214.

[10] Hamilton C.A., Cheung M.K., Osann K., Chen L., Teng N.N., Longacre T.A. et al.: “Uterine papillary serous and clear cell carcinomas predict for poorer survival compared to grade 3 endometrioid corpus cancers”. Br. J. Cancer, 2006, 94, 642.

[11] Alkushi A., Köbel M., Kalloger S.E., Gilks C.B.: “High-grade endometrial carcinoma: serous and grade 3 endometrioid carcinomas have different immunophenotypes and outcomes”. Int. J. Gynecol. Pathol., 2010, 29, 343.

[12] Fattaneh A., Tavassoli F.A., Devilee P. (eds.): “WHO classification of tumors pathology and genetics. Tumors of the breast and female genital organs”. Lyon, IARC Press, 2003, 276.

[13] Amant F., Moerman P., Neven P., Timmerman D., Van Limbergen E., Vergote I.: “Endometrial cancer”. Lancet, 2005, 366, 491.

[14] World Health Organization: World Mortality Report 2005. Available from web site: http://www.un.org/esa/population/publications/ worldmortality/WMR2005.pdf

[15] Ministry of Health, Labour and Welfare: Health and Nutrition Report. Available from website: http://www.mhlw.go.jp/houdou/ 2007/05/dl/h0516-3c_0003.pdf

[16] National Cancer Center: Cancer Information Service. Available from website: http://ganjoho.jp/pro/statistics/graph_db_index.html

[17] Society of Obstetrics and Gynecology: Annual reports by the committee of gynecologic oncology. Available from website: http://www.jsog.or.jp/activity/report.html

[18] Ueda S.M., Kapp D.S., Cheung M.K., Shin J.Y., Osann K., Husain A. et al.: “Trends in demographic and clinical characteristics in women diagnosed with corpus cancer and their potential impact on the increasing number of deaths”. Am. J. Obstet. Gynecol., 2008, 198, 218.

[19] Bristow R.E., Zerbe M.J., Rosenshein N.B., Grumbine F.C., Montz F.J.: “Stage IVB endometrial carcinoma: the role of cytoreductive surgery and determinants of survival”. Gynecol. Oncol., 2000, 78, 85.

[20] Ayhan A., Taskiran C., Celik C., Yuce K., Kucukali T.: “The influence of cytoreductive surgery on survival and morbidity in Stage IVB endometrial cancer”. Int. J. Gynecol. Cancer., 2002, 12, 448.

[21] Chi D.S., Welshinger M., Venkatraman E.S., Barakat R.R.: “The role of surgical cytoreduction in Stage IV endometrial carcinoma”. Gynecol. Oncol., 1997, 67, 56.

[22] Goldberg H., Miller R.C., Abdah-Bortnyak R., Steiner M., Yildiz F., Meirovitz A. et al., Rare Cancer Network: “Outcome after combined modality treatment for uterine papillary serous carcinoma: a study by the Rare Cancer Network (RCN)”. Gynecol. Oncol., 2008, 108, 298.

[23] Levenback C., Burke T.W., Silva E., Morris M., Gershenson D.M., Kavanagh J.J. et al.: “Uterine papillary serous carcinoma (UPSC) treated with cisplatin, doxorubicin, and cyclophosphamide (PAC)”. Gynecol. Oncol., 1992, 46, 317.

[24] Price F.V., Chambers S.K., Carcangiu M.L., Kohorn E.I., Schwartz P.E., Chambers J.T.: “Intravenous cisplatin, doxorubicin, and cyclophosphamide in the treatment of uterine papillary serous carcinoma (UPSC)”. Gynecol. Oncol., 1993, 51, 383.

[25] Zanotti K., Belinson J., Kennedy A., Webster K.D., Markman M.: “The use of paclitaxel and platinum-based chemotherapy in uterine papillary serous carcinoma”. Gynecol. Oncol., 1999, 74, 272.

[26] Ramondetta L., Burke T., Levenback C., Bevers M., Bodurka- Bevers D., Gershenson D.M.: “Treatment of uterine papillary serous carcinoma with paclitaxel”. Gynecol. Oncol., 2001, 82, 156.

[27] Landrum L.M., Moore K.N., Myers T.K., Lanneau G.S. Jr., McMeekin D.S., Walker J.L. et al.: “Stage IVB endometrial cancer: does applying an ovarian cancer treatment paradigm result in similar outcomes? A case-control analysis”. Gynecol. Oncol., 2009, 112, 337.

[28] Zorn K.K., Bonome T., Gangi L., Chandramouli G.V., Awtrey C.S., Gardner G.J.et al.: “Gene expression profiles of serous, endometrioid, and clear cell subtypes of ovarian and endometrial cancer”. Clin. Cancer. Res., 2005, 11, 6422.

[29] Oza A.M., Elit L., Tsao M.S., Kamel-Reid S., Biagi J., Provencher D.M. et al.: “Phase II study of temsirolimus in women with recurrent or metastatic endometrial cancer: a trial of the NCIC Clinical Trials Group”. J. Clin. Oncol., 2011, 29, 3278.

[30] Aghajanian C., Sill M.W., Darcy K.M., Greer B., McMeekin D.S., Rose P.G.et al.: “Phase II trial of bevacizumab in recurrent or persistent endometrial cancer: a Gynecologic Oncology Group study”. J. Clin. Oncol., 2011, 29, 2259.