Approach to adjuvant treatment of endometrial cancer
- Steven C Plaxe, MD
Steven C Plaxe, MD
- Professor, Reproductive Medicine
- Director, Gynecologic Oncology
- University of California, San Diego School of Medicine
- Arno J Mundt, MD
Arno J Mundt, MD
- Section Editor — Radiation Therapy
- Chairman of Radiation Oncology
- University of California, San Diego
- Section Editors
- Barbara Goff, MD
Barbara Goff, MD
- Section Editor — Gynecologic Oncology
- Professor of Gynecologic Oncology
- University of Washington
- Don S Dizon, MD, FACP
Don S Dizon, MD, FACP
- Section Editor – Gynecologic Oncology
- Clinical Co-Director, Gynecologic Oncology
- Founder and Director, The Oncology Sexual Health Clinic
- Massachusetts General Hospital Cancer Center
- Associate Professor of Medicine
- Harvard Medical School
The treatment of endometrial cancer following surgical staging is based on the risk of relapse and persistent disease, which is defined by the cancer stage at diagnosis and presence of prognostic factors. This topic will cover the risk stratification criteria for newly diagnosed endometrial cancer. The treatment by risk category is covered separately.
DEFINITION OF RISK BASED ON HISTOLOGY AND STAGE
For women with newly diagnosed endometrial cancer, treatment is stratified based on the risk of disease recurrence, which is characterized using the stage of disease (table 1), histology of the tumor, and other pathologic factors:
- Shah C, Johnson EB, Everett E, et al. Does size matter? Tumor size and morphology as predictors of nodal status and recurrence in endometrial cancer. Gynecol Oncol 2005; 99:564.
- Corpus Uteri. In: American Joint Committee on Cancer Staging Manual, 7th, Edge SB, Byrd DR, Compton CC, et al (Eds), Springer, New York 2010. p.403.
- Wethington SL, Barrena Medel NI, Wright JD, Herzog TJ. Prognostic significance and treatment implications of positive peritoneal cytology in endometrial adenocarcinoma: Unraveling a mystery. Gynecol Oncol 2009; 115:18.
- Garg G, Gao F, Wright JD, et al. Positive peritoneal cytology is an independent risk-factor in early stage endometrial cancer. Gynecol Oncol 2013; 128:77.
- Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet 2009; 105:103.
- Abu-Rustum NR, Zhou Q, Gomez JD, et al. A nomogram for predicting overall survival of women with endometrial cancer following primary therapy: toward improving individualized cancer care. Gynecol Oncol 2010; 116:399.
- Jolly S, Vargas CE, Kumar T, et al. The impact of age on long-term outcome in patients with endometrial cancer treated with postoperative radiation. Gynecol Oncol 2006; 103:87.
- Alektiar KM, Venkatraman E, Abu-Rustum N, Barakat RR. Is endometrial carcinoma intrinsically more aggressive in elderly patients? Cancer 2003; 98:2368.
- Creutzberg CL, van Putten WL, Koper PC, 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.
- Keys HM, Roberts JA, Brunetto VL, 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.
- Lee NK, Cheung MK, Shin JY, et al. Prognostic factors for uterine cancer in reproductive-aged women. Obstet Gynecol 2007; 109:655.
- Mundt AJ, Waggoner S, Yamada D, et al. Age as a prognostic factor for recurrence in patients with endometrial carcinoma. Gynecol Oncol 2000; 79:79.
- Grigsby PW, Perez CA, Kuten A, et al. Clinical stage I endometrial cancer: prognostic factors for local control and distant metastasis and implications of the new FIGO surgical staging system. Int J Radiat Oncol Biol Phys 1992; 22:905.
- Goodwin JS, Samet JM, Key CR, et al. Stage at diagnosis of cancer varies with the age of the patient. J Am Geriatr Soc 1986; 34:20.
- Samet J, Hunt WC, Key C, et al. Choice of cancer therapy varies with age of patient. JAMA 1986; 255:3385.
- Abu-Rustum NR, Alektiar K, Iasonos A, et al. The incidence of symptomatic lower-extremity lymphedema following treatment of uterine corpus malignancies: a 12-year experience at Memorial Sloan-Kettering Cancer Center. Gynecol Oncol 2006; 103:714.
- Kosary CL. FIGO stage, histology, histologic grade, age and race as prognostic factors in determining survival for cancers of the female gynecological system: an analysis of 1973-87 SEER cases of cancers of the endometrium, cervix, ovary, vulva, and vagina. Semin Surg Oncol 1994; 10:31.
- Hicks ML, Phillips JL, Parham G, et al. The National Cancer Data Base report on endometrial carcinoma in African-American women. Cancer 1998; 83:2629.
- Connell PP, Rotmensch J, Waggoner SE, Mundt AJ. Race and clinical outcome in endometrial carcinoma. Obstet Gynecol 1999; 94:713.
- Maxwell GL, Tian C, Risinger J, et al. Racial disparity in survival among patients with advanced/recurrent endometrial adenocarcinoma: a Gynecologic Oncology Group study. Cancer 2006; 107:2197.
- Clifford SL, Kaminetsky CP, Cirisano FD, et al. Racial disparity in overexpression of the p53 tumor suppressor gene in stage I endometrial cancer. Am J Obstet Gynecol 1997; 176:S229.
- Farley JH, Tian C, Rose GS, et al. Chemotherapy intensity and toxicity among black and white women with advanced and recurrent endometrial cancer: a Gynecologic Oncology Group Study. Cancer 2010; 116:355.
- Plaxe SC, Saltzstein SL. Impact of ethnicity on the incidence of high-risk endometrial carcinoma. Gynecol Oncol 1997; 65:8.
- Schimp VL, Ali-Fehmi R, Solomon LA, et al. The racial disparity in outcomes in endometrial cancer: could this be explained on a molecular level? Gynecol Oncol 2006; 102:440.
- Berchuck A, Rodriguez G, Kinney RB, et al. Overexpression of HER-2/neu in endometrial cancer is associated with advanced stage disease. Am J Obstet Gynecol 1991; 164:15.
- Hetzel DJ, Wilson TO, Keeney GL, et al. HER-2/neu expression: a major prognostic factor in endometrial cancer. Gynecol Oncol 1992; 47:179.
- Zhang MM, Cheung MK, Osann K, et al. Improved survival of Asians with corpus cancer compared with whites: an analysis of underlying factors. Obstet Gynecol 2006; 107:329.
- Singh M, Zaino RJ, Filiaci VJ, Leslie KK. Relationship of estrogen and progesterone receptors to clinical outcome in metastatic endometrial carcinoma: a Gynecologic Oncology Group Study. Gynecol Oncol 2007; 106:325.
- Silverman MB, Roche PC, Kho RM, et al. Molecular and cytokinetic pretreatment risk assessment in endometrial carcinoma. Gynecol Oncol 2000; 77:1.
- Salvesen HB, Das S, Akslen LA. Loss of nuclear p16 protein expression is not associated with promoter methylation but defines a subgroup of aggressive endometrial carcinomas with poor prognosis. Clin Cancer Res 2000; 6:153.
- Iwai K, Fukuda K, Hachisuga T, et al. Prognostic significance of progesterone receptor immunohistochemistry for lymph node metastases in endometrial carcinoma. Gynecol Oncol 1999; 72:351.
- Fukuda K, Mori M, Uchiyama M, et al. Prognostic significance of progesterone receptor immunohistochemistry in endometrial carcinoma. Gynecol Oncol 1998; 69:220.
- Gehrig PA, Van Le L, Olatidoye B, Geradts J. Estrogen receptor status, determined by immunohistochemistry, as a predictor of the recurrence of stage I endometrial carcinoma. Cancer 1999; 86:2083.
- Larson DM, Berg R, Shaw G, Krawisz BR. Prognostic significance of DNA ploidy in endometrial cancer. Gynecol Oncol 1999; 74:356.
- Minaguchi T, Yoshikawa H, Oda K, et al. PTEN mutation located only outside exons 5, 6, and 7 is an independent predictor of favorable survival in endometrial carcinomas. Clin Cancer Res 2001; 7:2636.
- Salvesen HB, Stefansson I, Kalvenes MB, et al. Loss of PTEN expression is associated with metastatic disease in patients with endometrial carcinoma. Cancer 2002; 94:2185.
- Black D, Soslow RA, Levine DA, et al. Clinicopathologic significance of defective DNA mismatch repair in endometrial carcinoma. J Clin Oncol 2006; 24:1745.
- Zighelboim I, Goodfellow PJ, Gao F, et al. Microsatellite instability and epigenetic inactivation of MLH1 and outcome of patients with endometrial carcinomas of the endometrioid type. J Clin Oncol 2007; 25:2042.
- Zighelboim I, Schmidt AP, Gao F, et al. ATR mutation in endometrioid endometrial cancer is associated with poor clinical outcomes. J Clin Oncol 2009; 27:3091.
- Myers AP. New strategies in endometrial cancer: targeting the PI3K/mTOR pathway--the devil is in the details. Clin Cancer Res 2013; 19:5264.
- Mackay HJ, Eisenhauer EA, Kamel-Reid S, et al. Molecular determinants of outcome with mammalian target of rapamycin inhibition in endometrial cancer. Cancer 2014; 120:603.
- Salvesen HB, Carter SL, Mannelqvist M, et al. Integrated genomic profiling of endometrial carcinoma associates aggressive tumors with indicators of PI3 kinase activation. Proc Natl Acad Sci U S A 2009; 106:4834.
- DEFINITION OF RISK BASED ON HISTOLOGY AND STAGE
- OTHER PROGNOSTIC FACTORS
- Lower uterine segment involvement
- Positive peritoneal cytology
- Older age
- Black women
- Molecular prognostic factors
- OVERVIEW OF TREATMENT
- Low-risk endometrial cancer
- Intermediate-risk endometrial cancer
- High-risk endometrial cancer
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS