Prognostic factors for types I and II epithelial ovarian cancer in the elderly

Purpose: No consensus exists on whether age is independently associated with poor prognosis in epithelial ovarian cancer (EOC). This study aimed to examine the prognostic factors of EOC in elderly patients. Materials and Methods:A total of 665 EOC patients from Jiangsu Institute of Cancer Research (JICR, People’s Republic of China) were retrospectively analyzed between 1996 and 2015. For validation, 990 cases who consulted at MD Anderson Cancer Center (MDACC, USA) from 1990 to 2011 were recruited. The associations between survival durations and covariates were assessed by Cox proportional hazards model and log-rank test. Results: Histological type II (p = 0.01) and suboptimal surgery outcome (p = 0.00) were more common in the elderly (age ≥ 70 years) patients with EOC than in younger patients from JICR. The International Federation of Gynecology and Obstetrics (FIGO) stage, histological type, and optimal surgery were independently associated with overall survival (OS; p = 0.00, p = 0.03, and p = 0.00, respectively) and progression-free survival (PFS; p = 0.00, p = 0.02, and p = 0.00, respectively) in the EOC patients. Both OS and PFS were lower in the elderly patients with type I EOC than in the younger cases (136.5 months vs. 191.8 months at p = 0.00 and 35.5 months vs. 75.1 months at p = 0.01, respectively). The OS and PFS of the elderly patients were poorer than those of the younger cases with type II EOC (38.4 months vs. 42.3 months at p = 0.00 and 14.9 months vs. 16.8 months, p = 0.04, respectively). In type II ovarian cancer patients who achieved optimal debulking, the median OS and PFS durations of younger patients remained longer than those of elderly patients (50.2 months vs. 68.0 months, p = 0.00 and 14.9 months vs. 19.2 months, p = 0.01, respectively). Conclusions: Compared with young patients, elderly EOC more commonly presented with an aggressive histological type and poor performance status and was more frequently undertreated. Advanced age was independently associated with poor prognosis in EOC, even after the influence of histological type and surgical outcome was eliminated.

Epithelial ovarian cancer; Prognostic factors; Advanced age.

[1] Miller K.D., Siegel R.L., Lin C.C., Mariotto A.B., Kramer J.L., Rowland J.H., et al.: “Cancer treatment and survivorship statistics, 2016”. CA: A Cancer Journal for Clinicians, 2016, 66, 271.

[2] Hannibal C.G., Cortes R., Engholm G., Kjaer S.K. “Survival of ovarian cancer patients in Denmark: excess mortality risk analysis of five-year relative survival in the period 1978-2002”. Acta Obstet. Gynecol. Scand., 2008, 87, 1353.

[3] Yang L., Parkin D. M., Whelan S., Zhang S., Chen Y., Lu F., et al.: “Statistics on cancer in China: cancer registration in 2002”. Eur. J. Cancer Prev., 2005, 14, 329.

[4] Chen W., Zheng R., Zeng H., Zhang S., He J. “Annual report on status of cancer in China, 2011”. Chin. J. Cancer Res., 2015, 27, 2.

[5] †F.B., Loos A.H., Tognazzo S., Vecchia C.L.: “Ovarian cancer in Europe: Cross-sectional trends in incidence and mortality in 28 countries, 1953–2000”. Int. J. Cancer, 2005, 113, 977.

[6] Zhou J., He Z.Y., Li F.Y., Sun J.Y., Lin H.X., Wu S.G., et al.: “Prognostic value of lymph node ratio in stage IIIC epithelial ovarian cancer with node-positive in a SEER population-based study”. Oncotarget, 2016, 7, 7952.

[7] Rauh-Hain J.A., Diver E.J., Clemmer J.T., Bradford L.S., Clark R. M., Growdon W.B., et al.: “Carcinosarcoma of the ovary compared to papillary serous ovarian carcinoma: a SEER analysis”. Gynecol. Oncol., 2013, 131, 46.

[8] Terplan M., Schluterman N., McNamara E.J., Tracy J.K., Temkin S.M. “Have racial disparities in ovarian cancer increased over time? An analysis of SEER data”. Gynecol. Oncol., 2012, 125, 19.

[9] Rouzier R., Bergzoll C., Brun J. L., Dubernard G., Selle F., Uzan S., et al.: “The role of lymph node resection in ovarian cancer: analysis of the Surveillance, Epidemiology, and End Results (SEER) database”. BJOG, 2010, 117, 1451.
[10] Gibson S.J., Fleming G.F., Temkin S.M., Chase D.M. “The Application and Outcome of Standard of Care Treatment in Elderly Women with Ovarian Cancer: A Literature Review over the Last 10 Years”. Front. Oncol., 2016, 6, 63.

[11] Langstraat C., Cliby W.A.: “Considerations in the surgical management of ovarian cancer in the elderly”. Curr. Treat. Options Oncol., 2013, 14, 12.

[12] Malvezzi M., Carioli G., Rodriguez T., Negri E., La Vecchia C.: “Global trends and predictions in ovarian cancer mortality”. Ann. Oncol., 2016, 27, 2017.

[13] Sabatier R., Calderon B. Jr., Lambaudie E., Chereau E., Provansal M., Cappiello M. A., et al.: “Prognostic factors for ovarian epithelial cancer in the elderly: a case-control study”. Int. J. Gynecol. Cancer, 2015, 25, 815.

[14] Uyar D., Frasure H.E., Markman M., von Gruenigen V.E.: “Treatment patterns by decade of life in elderly women (> or =70 years of age) with ovarian cancer”. Gynecol. Oncol., 2005, 98, 403.

[15] Aletti G.D., Eisenhauer E.L., Santillan A., Axtell A., Aletti G., Holschneider C., et al.: “Identification of patient groups at highest risk from traditional approach to ovarian cancer treatment”. Gynecol. Oncol., 2011, 120, 23.

[16] Xu X., Chen X., Dai Z., Deng F., Qu J., Ni J.: “Secondary cytoreduction surgery improves prognosis in platinum-sensitive recurrent ovarian cancer”. J. Exp. Clin. Cancer Res., 2013, 32, 61.

[17] Chen X., Zhang J., Zhang Z., Li H., Cheng W., Liu J.: “Cancer stem cells, epithelial-mesenchymal transition, and drug resistance in highgrade ovarian serous carcinoma”. Hum. Pathol., 2013, 44, 2373.

[18] Chen X., Zhang J., Cheng W., Chang D. Y., Huang J., Wang X., et al.: “CA-125 level as a prognostic indicator in type I and type II epithelial ovarian cancer”. Int. J. Gynecol. Cancer, 2013, 23, 815.

[19] Xu X., Wang Y., Wang F., Jia L., Zhou Y., Deng F., et al.: “Nadir CA-125 level as prognosis indicator of high-grade serous ovarian cancer”. J. Ovarian Res., 2013, 6, 31.

[20] Wang F., Ye Y., Xu X., Zhou X., Wang J., Chen X.: “CA-125-indicated asymptomatic relapse confers survival benefit to ovarian cancer patients who underwent secondary cytoreduction surgery”. J. Ovarian Res., 2013, 6, 14.

[21] Balducci L., Cohen H.J., Engstrom P.F., Ettinger D.S., Halter J., Gordon L.I., et al.: “Senior adult oncology clinical practice guidelines in oncology”. J. Natl. Compr. Canc. Netw., 2005, 3, 572.

[22] Balducci L.: “Management of cancer in the elderly”. Oncology (Williston Park), 2006, 20, 135.

[23] Barber E.L., Rutstein S., Miller W. C., Gehrig P.A.: “A preoperative personalized risk assessment calculator for elderly ovarian cancer patients undergoing primary cytoreductive surgery”. Gynecol. Oncol., 2015, 139, 401.

[24] Turrentine F.E., Wang H., Simpson V. B., Jones R.S. “Surgical risk factors, morbidity, and mortality in elderly patients”. J. Am. Coll. Surg., 2006, 203, 865.

[25] Gerestein C.G., Damhuis R.A., de Vries M., Reedijk A., Burger C.W., Kooi G.S.: “Causes of postoperative mortality after surgery for ovarian cancer”. Eur. J. Cancer, 2009, 45, 2799.

[26] Barber E.L., Rutstein S.E., Miller W.C., Gehrig P.A.: “Corrigendum to 'A preoperative personalized risk assessment calculator for elderly ovarian cancer patients undergoing primary cytoreductive surgery'” Gynecol. Oncol., 2016, 142, 380. [27] Joseph N., Clark R.M., Dizon D.S., Lee M.S., Goodman A., Boruta D. Jr., et al.: “Delay in chemotherapy administration impacts survival in elderly patients with epithelial ovarian cancer”. Gynecol. Oncol., 2015, 137, 401.

[28] Bun S., Yunokawa M., Ebata T., Shimomura A., Shimoi T., Kodaira M., et al.: “Feasibility of dose-dense paclitaxel/carboplatin therapy in elderly patients with ovarian, fallopian tube, or peritoneal cancer”. Cancer Chemother. Pharmacol., 2016, 78, 745.

[29] Corvino R., De Iuliis F., D'Aniello D., Cefali K., Ferraro E., Lamazza A., et al.: “Long-Lasting Stent Placement in an Elderly Advanced Ovarian Cancer Patient”. Oncol. Res. Treat., 2016, 39, 146.

[30] Fourcadier E., Tretarre B., Gras-Aygon C., Ecarnot F., Daures J. P., Bessaoud F.: “Under-treatment of elderly patients with ovarian cancer: a population based study”. BMC Cancer, 2015, 15, 937.

[31] Cafa E.V., Pecorino B., Scibilia G., Scollo P.: “Role of Surgery in the Elderly Patients Affected from Advanced Stage Ovarian Cancer”. J. Cancer Ther., 2015, 6, 428.

[32] Sharma S., Driscoll D., Odunsi K., Venkatadri A., Lele S. “Safety and efficacy of cytoreductive surgery for epithelial ovarian cancer in elderly and high-risk surgical patients”. Am. J. Obstet. Gynecol., 2005, 193, 2077.

[33] Susini T., Amunni G., Busi E., Villanucci A., Carriero C., Taddei G., et al.: “Ovarian cancer in the elderly: feasibility of surgery and chemotherapy in 89 geriatric patients”. Int. J. Gynecol. Cancer, 2007, 17, 581.

[34] Janda M., Youlden D. R., Baade P.D., Jackson D., Obermair A.: “Elderly patients with stage III or IV ovarian cancer: should they receive standard care?”. Int. J. Gynecol. Cancer, 2008, 18, 896.

[35] Therasse P., Arbuck S.G., Eisenhauer E.A., Wanders J., Kaplan R.S., Rubinstein L., et al.: “New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada”. J. Natl. Cancer Inst., 2000, 92, 205.

[36] Woopen H., Inci G., Richter R., Chekerov R., Ismaeel F., Sehouli J.: “Elderly ovarian cancer patients: An individual participant data metaanalysis of the North-Eastern German Society of Gynecological Oncology (NOGGO)”. Eur. J. Cancer, 2016, 60, 101.

[37] Chia V.M., O'Malley C.D., Danese M.D., Lindquist K.J., Gleeson M.L., Kelsh M.A., et al.: “Prevalence and incidence of comorbidities in elderly women with ovarian cancer”. Gynecol. Oncol., 2013, 129, 346.

[38] Mooney S.J., Winner M., Hershman D.L., Wright J.D., Feingold D.L., Allendorf J.D., et al.: “Bowel obstruction in elderly ovarian cancer patients: a population-based study”. Gynecol. Oncol., 2013, 129, 107.

[39] Trillsch F., Woelber L., Eulenburg C., Braicu I., Lambrechts S., Chekerov R., et al.: “Treatment reality in elderly patients with advanced ovarian cancer: a prospective analysis of the OVCAD consortium”. J. Ovarian Res., 2013, 6, 42.

[40] Tew W.P.: “Considerations regarding the administration of systemic therapy for elderly patients with ovarian cancer”. Curr. Treat. Options Oncol., 2013, 14, 1.

[41] Pignata S., Vermorken J.B.: “Ovarian cancer in the elderly”. Crit. Rev. Oncol. Hematol., 2004, 49, 77.

[42] Jørgensen T.L., Teiblum S., Paludan M., Poulsen L.Ø., Jørgensen A.Y., Bruun K.H., et al.: “Significance of age and comorbidity on treatment modality, treatment adherence, and prognosis in elderly ovarian cancer patients”. Gynecol. Oncol., 2012, 127, 367.

[43] Jordan S., Steer C., Defazio A., Quinn M., Obermair A., Friedlander M., et al.: “Patterns of chemotherapy treatment for women with invasive epithelial ovarian cancer – A population-based study”. Gynecol. Oncol., 2013, 129, 310.

[44] Fourcadier E., Trétarre B., Gras-Aygon C., Ecarnot F., Daurès J. P., Bessaoud F.: “Under-treatment of elderly patients with ovarian cancer: a population based study”. BMC Cancer, 2015, 15, 1.

[45] Thigpen T., Brady M. F., Omura G. A., Creasman W. T., Mcguire W. P., Hoskins W. J., et al.: “Age as a prognostic factor in ovarian carcinoma: The gynecologic oncology group experience”. Cancer, 1993, 71, 606. [46] Kurman R.J., Iem S.: “The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory”. Am. J. Surg. Pathol., 2010, 34, 433.

[47] Muralikrishnan S., Hatzis C., Katz A., Santin A., Schwartz P.E., AbuKhalaf M.M.: “Chemotherapy for Elderly Ovarian Cancer Patients”. Gynecol. Obstet. (Sunnyvale), 2016, 6. pii: 397. Epub 2016 Aug 31.

[48] Poonawalla I.B., Piller L.B., Lairson D.R., Chan W., Du X.L.: “Impact of Hematopoietic Growth Factors on Blood Transfusion Needs, Incidence of Neutropenia, and Overall Survival Among Elderly Advanced Ovarian Cancer Patients Treated With Chemotherapy”. Int. J. Gynecol. Cancer, 2016, 26, 95.

[49] Tinquaut F., Freyer G., Chauvin F., Gane N., Pujade-Lauraine E., Falandry C.: “Prognostic factors for overall survival in elderly patients with advanced ovarian cancer treated with chemotherapy: Results of a pooled analysis of three GINECO phase II trials”. Gynecol. Oncol., 2016, 143, 22.

[50] Wright J.D., Ananth C.V., Tsui J., Glied S.A., Burke W.M., Lu Y. S., et al.: “Comparative effectiveness of upfront treatment strategies in elderly women with ovarian cancer”. Cancer, 2014, 120, 1246.

[51] Falandry C., Weber B., Savoye A. M., Tinquaut F., Tredan O., Sevin E., et al.: “Development of a geriatric vulnerability score in elderly patients with advanced ovarian cancer treated with first-line carboplatin: a GINECO prospective trial”. Ann. Oncol., 2013, 24, 2808.