The impact of adjuvant therapy on survival in patients with FIGO Stage IB Grade 3 endometrial cancer

Purpose of Investigation: To examine the patterns of care, predictors, and impact of adjuvant therapy on survival in patients with Stage IB Grade 3 endometrial cancer. Materials and Methods: The Surveillance, Epidemiology, and End Results (SEER)-Medicare database was used to identify women 65 years or older diagnosed with Stage IB Grade 3 endometrial cancer from 1991 through 2007. Results: A total of 624 women were included. Adjuvant external beam radiation therapy (EBRT) was administered in 54% of the patients, while 22% received vaginal brachytherapy (VBT), and 7% received chemotherapy. In Cox-proportional hazards regression models, neither EBRT (HR: 0.94; 95% CI; 0.71–1.22), nor VBT (HR: 0.84; 95% CI: 0.60–1.17), or chemotherapy (HR: 1.30: 95% CI; 0.64–2.66) was associated with reduced mortality in patients with Stage IB Grade 3 endometrial cancer. Conclusion: Although commonly used; neither adjuvant radiation nor chemotherapy significantly improves survival in patients with Stage IB Grade 3 endometrial cancer.

Endometrial cancer; Adjuvant therapy; Survival.

[1] Siegel R.L., Miller K.D., Jemal A.: “Cancer statistics, 2015”. CA Cancer J. Clin., 2015, 65, 5.

[2] Morrow C.P., Bundy B.N., Kurman R.J., Creasman W.T., Heller P., Homesley H.D., et al.: “Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: a Gynecologic Oncology Group study”. Gynecol. Oncol., 1991, 40, 55.

[3] Alektiar K.M., McKee A., Lin O., Venkatraman E., Zelefsky M.J., Mychalczak B.R., et al.: “The significance of the amount of myometrial invasion in patients with Stage IB endometrial carcinoma”. Cancer, 2002, 95, 316.

[4] Weinberg L.E., Kunos C.A., Zanotti K.M.: “Lymphovascular space invasion (LVSI) is an isolated poor prognostic factor for recurrence and survival among women with intermediate- to high-risk earlystage endometrioid endometrial cancer”. Int. J. Gynecol. Cancer, 2013, 23, 1438.

[5] Mariani A., Dowdy S.C., Keeney G.L., Long H.J., Lesnick T.G., Podratz K.C.: “High-risk endometrial cancer subgroups: candidates for target-based adjuvant therapy”. Gynecol. Oncol., 2004, 95, 120.

[6] Gadducci A., Cavazzana A., Cosio S., DI Cristofano C., Tana R., Fanucchi A., et al.: “Lymph-vascular space involvement and outer one-third myometrial invasion are strong predictors of distant haematogeneous failures in patients with stage I-II endometrioidtype endometrial cancer”. Anticancer Res., 2009, 29, 1715.

[7] Meerwaldt J.H., Hoekstra C.J., van Putten W.L., Tjokrowardojo A.J., Koper P.C.: “Endometrial adenocarcinoma, adjuvant radiotherapy tailored to prognostic factors”. Int. J. Radiat. Oncol. Biol. Phys., 1990, 18, 299.

[8] Creasman W.T., Morrow C.P., Bundy B.N., Homesley H.D., Graham J.E., Heller P.B.: “Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study”. Cancer, 1987, 60, 2035.

[9] www.nccn.org/professionals/physician_gls/pdf/uterine.pdf

[10] Wright J.D., Lewin S.N., Barrena Medel N.I., Sun X., Burke W.M., Deutsch I., et al.: “Endometrial cancer in the oldest old: Tumor characteristics, patterns of care, and outcome”. Gynecol Oncol., 2011, 122, 69.

[11] Truong P.T., Kader H.A., Lacy B., Lesperance M., MacNeil M.V., Berthelet E., et al.: “The effects of age and comorbidity on treatment and outcomes in women with endometrial cancer”. Am. J. Clin. Oncol., 2005, 28, 157.

[12] Keys H.M., Roberts J.A., Brunetto V.L., Zaino R.J., Spirtos N.M., Bloss J.D., et al.: “A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study”. Gynecol. Oncol., 2004, 92, 744.

[13] Creutzberg C.L., van Putten W.L., Koper P.C., Lybeert M.L., Jobsen J.J., Warlam-Rodenhuis C.C., et al.: “Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC Study Group. Post Operative Radiation Therapy in Endometrial Carcinoma”. Lancet, 2000, 355, 1404.

[14] Hogberg T., Signorelli M., de Oliveira C.F., Fossati R., Lissoni A.A., Sorbe B., et al.: “Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer—results from two randomised studies”. Eur. J. Cancer, 2010, 46, 2422.

[15] Susumu N., Sagae S., Udagawa Y., Niwa K., Kuramoto H., Satoh S., et al.: “Randomized phase III trial of pelvic radiotherapy versus cisplatin- based combined chemotherapy in patients with intermediateand high-risk endometrial cancer: a Japanese Gynecologic Oncology Group study”. Gynecol. Oncol., 2008, 108, 226.

[16] Maggi R., Lissoni A., Spina F., Melpignano M., Zola P., Favalli G., et al.: “Adjuvant chemotherapy vs radiotherapy in high-risk endometrial carcinoma: results of a randomised trial”. Br. J. Cancer, 2006, 95, 266.

[17] Nout R.A., Smit V.T., Putter H., Jurgenliemk-Schulz I.M., Jobsen J.J., Lutgens L.C., et al.: “Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial”. Lancet, 2010, 375, 816.

[18] Wright J.D., Neugut A.I., Wilde E.T., Buono D.L., Malin J., Tsai W.Y., et al.: “Physician characteristics and variability of erythropoiesis- stimulating agent use among Medicare patients with cancer”. J. Clin. Oncol., 2011, 29, 3408.

[19] Klabunde C.N., Warren J.L., Legler J.M.: “Assessing comorbidity using claims data: an overview”. Med. Care, 2002, 40, IV-26.

[20] Klabunde C.N., Potosky A.L., Legler J.M., Warren J.L.: “Development of a comorbidity index using physician claims data”. J. Clin. Epidemiol., 2000, 53, 1258.

[21] Wright J.D., Fiorelli J., Schiff P.B., Burke W.M., Kansler A.L., Cohen C.J., et al.: “Racial disparities for uterine corpus tumors: changes in clinical characteristics and treatment over time”. Cancer, 2009, 115, 1276.

[22] 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.

[23] Naumann R.W., Coleman R.L.: “The use of adjuvant radiation therapy in early endometrial cancer by members of the Society of Gynecologic Oncologists in 2005”. Gynecol. Oncol., 2007, 105, 7.

[24] Aalders J., Abeler V., Kolstad P., Onsrud M.: “Postoperative external irradiation and prognostic parameters in stage I endometrial carcinoma: clinical and histopathologic study of 540 patients”. Obstet. Gynecol., 1980, 56, 419.

[25] Klopp A., Smith B.D., Alektiar K., Cabrera A., Damato A.L., Erickson B., et al.: “The role of postoperative radiation therapy for endometrial cancer: Executive summary of an American Society for Radiation Oncology evidence-based guideline”. Pract. Radiat. Oncol., 2014, 4, 137.

[26] Creutzberg C.L., van Putten W.L., Warlam-Rodenhuis C.C., van den Bergh A.C., de Winter K.A., Koper P.C., et al.: “Outcome of highrisk stage IC, grade 3, compared with stage I endometrial carcinoma patients: the Postoperative Radiation Therapy in Endometrial Carcinoma Trial”. J. Clin. Oncol., 2004, 22, 1234.

[27] Suh D.H., Lee K.H., Kim K., Kang S., Kim J.W.: “Major clinical research advances in gynecologic cancer in 2014”. J. Gynecol. Oncol., 2015, 26, 156.

[28] Group A.S., Kitchener H., Swart A.M., Qian Q., Amos C., Parmar M.K.: “Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study”. Lancet, 2009, 373, 125.

[29] Panici P.B., Maggioni A., Hacker N., Landoni F., Ackermann S., Campagnutta E., et al.: “Systematic aortic and pelvic lymphadenectomy versus resection of bulky nodes only in optimally debulked advanced ovarian cancer: a randomized clinical trial”. J. Natl. Cancer Inst., 2005, 97, 560.

[30] Le T., Adolph A., Krepart G.V., Lotocki R., Heywood M.S.: “The benefits of comprehensive surgical staging in the management of earlystage epithelial ovarian carcinoma”. Gynecol Oncol., 2002, 85, 351.