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Approach to adjuvant treatment of endometrial cancer - UpToDate 3/17/17, 10:03 AM https://www.uptodate.com/contents/approach-to-adjuvant-treatment-of-endometrial-cancer/print?source=see_link Page 1 of 11 Official reprint from UpToDate www.uptodate.com ©2017 UpToDate The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of UpToDate content is governed by the UpToDate Terms of Use. ©2017 UpToDate, Inc. All rights reserved. Approach to adjuvant treatment of endometrial cancer Authors: Steven C Plaxe, MD, Arno J Mundt, MD Section Editors: Barbara Goff, MD, Don S Dizon, MD, FACP Deputy Editor: Sadhna R Vora, MD All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Feb 2017. | This topic last updated: Jan 04, 2016. INTRODUCTION — 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: ® ® ● (See "Treatment of low-risk endometrial cancer".) ● (See "Adjuvant treatment of intermediate-risk endometrial cancer".) ● (See "Adjuvant treatment of high-risk endometrial cancers".) Low-risk endometrial cancer includes women with grade 1 endometrial cancer of endometrioid histology that is confined to the endometrium (a subset of stage IA disease). The overall probability of recurrence in these groups is very low following surgical treatment alone. ● Intermediate-risk endometrial cancer includes women with uterine-limited cancer that invades the myometrium (stage IA or IB) or demonstrates occult cervical stromal invasion (stage II). These groups have a higher risk of recurrence than do patients whose tumors are confined to the endometrium (which defines patients with low-risk endometrial cancer). Among this subgroup, there are other adverse prognostic factors used to stratify women into high and lowintermediate- risk. These include outer one-third myometrial invasion, grade 2 or 3 differentiation, or the presence of lymphovascular invasion within the cancer. (See "Adjuvant treatment of intermediate-risk ● Approach to adjuvant treatment of endometrial cancer - UpToDate 3/17/17, 10:03 AM https://www.uptodate.com/contents/approach-to-adjuvant-treatment-of-endometrial-cancer/print?source=see_link Page 2 of 11 Staging evaluations and discussion of the role of the sentinel lymph node biopsy are discussed in detail elsewhere. (See "Endometrial carcinoma: Pretreatment evaluation, staging, and surgical treatment", section on 'Pretreatment evaluation' and "Endometrial carcinoma: Pretreatment evaluation, staging, and surgical treatment".) OTHER PROGNOSTIC FACTORS — Beyond histology and stage, other factors may be used to inform the role of adjuvant therapy beyond the risk-stratified approach described above. These include: Lower uterine segment involvement — Women with otherwise low-risk disease who have involvement of the lower uterine segment may be at a greater risk for nodal involvement. However, it is not clear if involvement of the lower uterine segment represents an independent risk factor for survival. This topic is discussed in detail separately. (See "Treatment of low-risk endometrial cancer".) Positive peritoneal cytology — Approximately 11 percent of patients undergoing surgical staging have positive peritoneal cytology, most commonly in the setting of advanced (extrauterine) disease [1]. However, positive peritoneal cytology is no longer considered in the staging system for endometrial carcinoma to assign tumor (T) stage (table 1) [2]. Despite this, the prognostic significance of isolated positive peritoneal washings in the absence of extrauterine spread remains controversial, as illustrated in the following studies: endometrial cancer", section on 'Definition of intermediate-risk'.) High-risk endometrial cancer includes women with stage III or higher endometrial cancer, regardless of histology or grade. However, women with a serous (USC) or clear cell (CC) carcinoma are deemed at high risk, regardless of stage. These women are at a high risk of relapse and death. ● A 2009 systematic review that included over 50 studies reported that the prognosis associated with a positive peritoneal cytology varied according to the presence of other factors [3]. Women with positive peritoneal cytology, but otherwise low-risk disease (grade 1 or 2, myometrial invasion <50 percent, no cervical involvement, no lymphovascular space invasion) had a significantly lower rate of recurrence compared with other women (4.1 versus 32 percent). ● However, a 2012 analysis of 14,704 patients identified from the Surveillance, Epidemiology, and End Results (SEER) registry reported that positive peritoneal cytology was an independent predictor of mortality, regardless of histologic subtype, among women with early-stage (stage I to II) endometrial carcinoma [4]. The main results were: ● Patients with high-risk factors (eg, grade 3 disease, clear cell or serous histology) were more likely to have positive peritoneal cytology than those without high-risk factors (17.5 versus 7.5 percent, respectively, p <0.0001). • The presence of positive peritoneal cytology predicted significantly poorer survival regardless of histology and tumor grade compared with those with negative cytologic results. • The risk of death was significantly higher among women with positive peritoneal cytology compared with those with negative peritoneal cytology and stage IA disease (hazard ratio [HR] 4.6, 95% CI 3.79- 5.66). • Approach to adjuvant treatment of endometrial cancer - UpToDate 3/17/17, 10:03 AM https://www.uptodate.com/contents/approach-to-adjuvant-treatment-of-endometrial-cancer/print?source=see_link Page 3 of 11 We do not routinely consider peritoneal cytology results by themselves in the formulation of a treatment plan for patients with endometrial cancer and continue to make treatment decisions primarily based on extent of disease (determined at staging) and final pathologic features. We agree with the 2009 International Federation of Gynecology and Obstetrics (FIGO) staging guidelines for endometrial cancer and report cytology results separately without adjustment to the T-stage [5]. (See "Endometrial carcinoma: Pretreatment evaluation, staging, and surgical treatment", section on 'Staging and primary surgical treatment'.) Older age — Older age has been associated with higher rates of clinical failure and survival in several [6-11] (but not all [12]) studies. The association between age and prognosis can be illustrated by data from the Gynecologic Oncology Group (GOG) protocol 33, in which five-year relative survival rates for women with clinical stage I and II endometrial cancer stratified by age were as follows: Whether age represents an independent prognostic factor is controversial. Women over the age of 65 have more frequent deep myometrial invasion, high tumor grade, and advanced tumor stage [7,12-15]. Furthermore, less aggressive therapy could also account for some of the poor outcomes seen in older patients [12,14,15]. As noted above, age is used to categorize women with intermediate-risk disease into either a high or low-intermediate risk group, which may influence treatment decisions. However, even when treated in uniform fashion, older women seem to have higher recurrence rates and inferior survival compared with their younger counterparts. (See 'Definition of risk based on histology and stage' above.) Black women — Race also factors into prognosis. Black women have a consistently poorer outcome than Caucasians, an effect that is incompletely explained by imbalances in psychosocial, clinicopathologic, and treatment factors [16-22]. Some of the racial disparity in survival has been attributed to a lower incidence of good-prognosis (low-grade endometrioid) cancers in blacks and a higher incidence of high-risk (grade 3 and nonendometrioid) tumors [23,24]. However, an alternative explanation for the worse survival is provided by emerging data suggesting that at least in uterine serous cancers, blacks have a higher frequency of overexpressed or amplified human epidermal growth factor receptor 2 (HER2) [25,26]. In contrast to Black women, Asian women appear to have a better survival relative to other populations, an effect that is attributed at least in part to younger age at diagnosis. In data from the SEER of the National Cancer Institute, 1 in 50 Asian women with uterine cancer was diagnosed before age 35 as compared with 1 in 150 white women [27]. Molecular prognostic factors — A number of molecular factors hold promise for determining the prognostic value of routine surgical and histologic characteristics. These include p53 and p16 overexpression, phosphatase and tensin homolog (PTEN) mutations, markers of proliferation, microsatellite instability, tumor expression of estrogen (ER) and/or progesterone (PR) receptors, or proteins involved in the phosphoinositide 3-kinase ● ≤40 years old – 96 percent ● 41 to 50 years old – 94 percent ● 51 to 60 years old – 87 percent ● 61 to 70 years old – 78 percent ● 71 to 80 years old – 71 percent ● ≥80 years old – 54 percent Approach to adjuvant treatment of endometrial cancer - UpToDate 3/17/17, 10:03 AM https://www.uptodate.com/contents/approach-to-adjuvant-treatment-of-endometrial-cancer/print?source=see_link Page 4 of 11 (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway [28-41]. Until more data become available, however, they remain investigational and should not be incorporated into clinical decision making. As examples: OVERVIEW OF TREATMENT — All women with endometrial cancer should undergo surgical staging, especially if the disease is not suspected to be metastatic. For these women, the treatment approach is based on final pathology and the histologic type of cancer, which are used to define risk (see 'Definition of risk based on histology and stage' above): Low-risk endometrial cancer — For women with low-risk endometrial cancer, no adjuvant treatment is indicated following surgery. However, some women may wish to preserve future fertility, despite a biopsy-proven diagnosis of grade 1 endometrial cancer. These patients may be candidates for conservative treatment using progestin therapy (eg, megestrol acetate), although careful selection of appropriate patients is necessary. (See "Treatment of low-risk endometrial cancer".) Intermediate-risk endometrial cancer — Women with intermediate-risk endometrial cancer benefit most from postoperative radiation therapy (RT). However, some clinicians may offer adjuvant chemotherapy (with or without In a report of 134 women who underwent complete surgical staging, p53 overexpression and high S phase fraction (≥9 percent) in preoperative endometrial curettage specimens were independent, significant, presurgical molecular determinants of outcome. The presence of both factors increased the risk of recurrence sevenfold, and the risk of cancer-related death almost 10-fold when compared with women with neither factor [29]. ● The absence of PR expression has been correlated with the presence of lymph node metastases and inferior survival in some reports [31,32]. Absence of ER expression appears to have some prognostic value, but less than PR expression [33]. ● Many series report a more favorable outcome for women whose endometrial cancers arise in the setting of Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC]), but there may be subsets with a poorer prognosis. Within the subgroup of endometrioid endometrial tumors with high-level microsatellite instability (MSI-H), tumors that harbor mutations in the cell cycle checkpoint gene, ATR have a significantly worse prognosis than those with a wild-type ATR gene [39]. (See "Endometrial and ovarian cancer screening and prevention in women with Lynch syndrome (hereditary nonpolyposis colorectal cancer)".) ● Mutations involving the PI3K/AKT/mTOR pathway appear to be associated with prognosis. For example, in one report, amplifications of the catalytic subunits of PI3K (PI3KCA) were significantly associated with poorer recurrence-free survival compared with those without amplification [42]. Therefore, targeting of this pathway appears to be a promising approach to patients with endometrial cancer. Strategies directed at targeting aberrations in the PI3K/AKT/mTOR pathway include rapalogs, inhibitors of either PI3K or mTOR individually or together, and inhibition of AKT [40]. However, one retrospective review of patients treated with mTOR inhibitors in phase II studies did not identify a predictive biomarker for sensitivity to mTOR inhibition [41]. ● Approach to adjuvant treatment of endometrial cancer - UpToDate 3/17/17, 10:03 AM https://www.uptodate.com/contents/approach-to-adjuvant-treatment-of-endometrial-cancer/print?source=see_link Page 5 of 11 RT) to women with higher risk intermediate-risk endometrial cancer, although the benefit of this approach is not clear. Therefore, whenever possible, we prefer to offer treatment on clinical trials. (See "Adjuvant treatment of intermediate-risk endometrial cancer".) High-risk endometrial cancer — Women with high-risk endometrial cancers undergoing surgery should be offered adjuvant chemotherapy. Whether there is an additional benefit to RT is not entirely clear. Therefore, we believe these patients should be offered participation in appropriate clinical trials, such as Gynecologic Oncology Group (GOG) 258, a phase III trial of chemotherapy (carboplatin and paclitaxel) with or without cisplatin and RT. (See "Adjuvant treatment of high-risk endometrial cancers".) INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) SUMMARY AND RECOMMENDATIONS th th th th Beyond the Basics topics (see "Patient education: Endometrial cancer diagnosis and staging (Beyond the Basics)" and "Patient education: Endometrial cancer treatment after surgery (Beyond the Basics)") ● For women with newly diagnosed endometrial cancer, the risk of recurrence is used to categorize women as having low, intermediate, or high-risk endometrial cancer. In general, this is based on tumor histology and pathologic stage. (See 'Definition of risk based on histology and stage' above.) ● Beyond stage and tumor histology, other factors may be used to individualize risk further. These include lower uterine segment involvement, older age, and race. (See 'Other prognostic factors' above.) ● While molecular characterization of the tumor can help distinguish risk, more data are needed before we utilize this information for tailoring adjuvant treatment. (See 'Molecular prognostic factors' above.) ● Women with low-grade (grade 1 or 2) endometrioid cancers confined to the endometrium (a subset of stage IA disease) are classified as having low-risk endometrial cancer. Because their prognosis following surgery is excellent, no adjuvant treatment is required. (See 'Low-risk endometrial cancer' above.) ● Women with endometrial cancer that invades the myometrium (stage IA or IB) or demonstrates occult cervical stromal invasion (stage II) have intermediate-risk disease. These patients are candidates for adjuvant radiation therapy (RT). Although there is no clear role for chemotherapy as part of an adjuvant treatment strategy, some clinicians recommend chemotherapy to women with high intermediate-risk disease. (See 'Intermediate-risk endometrial cancer' above.) ● Approach to adjuvant treatment of endometrial cancer - UpToDate 3/17/17, 10:03 AM https://www.uptodate.com/contents/approach-to-adjuvant-treatment-of-endometrial-cancer/print?source=see_link Page 6 of 11 REFERENCES 1. 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. 2. 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. 3. 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. 4. 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. 5. Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet 2009; 105:103. 6. 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. 7. 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. 8. Alektiar KM, Venkatraman E, Abu-Rustum N, Barakat RR. Is endometrial carcinoma intrinsically more aggressive in elderly patients? Cancer 2003; 98:2368. 9. 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. 10. 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. 11. Lee NK, Cheung MK, Shin JY, et al. Prognostic factors for uterine cancer in reproductive-aged women. Obstet Gynecol 2007; 109:655. 12. 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. 13. 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. 14. 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. 15. Samet J, Hunt WC, Key C, et al. Choice of cancer therapy varies with age of patient. JAMA 1986; Women who have any of the following features have high-risk endometrial cancer: stage III disease, regardless of histology or grade; and/or uterine serous carcinoma (USC) or clear cell carcinoma (CC) of any stage. Women with high-risk disease often receive chemotherapy with or without RT given their high risk of both distant and locoregional relapse. (See 'High-risk endometrial cancer' above.) ● Approach to adjuvant treatment of endometrial cancer - UpToDate 3/17/17, 10:03 AM https://www.uptodate.com/contents/approach-to-adjuvant-treatment-of-endometrial-cancer/print?source=see_link Page 7 of 11 255:3385. 16. 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. 17. 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. 18. 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. 19. Connell PP, Rotmensch J, Waggoner SE, Mundt AJ. Race and clinical outcome in endometrial carcinoma. Obstet Gynecol 1999; 94:713. 20. 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. 21. 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. 22. 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. 23. Plaxe SC, Saltzstein SL. Impact of ethnicity on the incidence of high-risk endometrial carcinoma. Gynecol Oncol 1997; 65:8. 24. 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. 25. 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. 26. Hetzel DJ, Wilson TO, Keeney GL, et al. HER-2/neu expression: a major prognostic factor in endometrial cancer. Gynecol Oncol 1992; 47:179. 27. 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. 28. 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. 29. Silverman MB, Roche PC, Kho RM, et al. Molecular and cytokinetic pretreatment risk assessment in endometrial carcinoma. Gynecol Oncol 2000; 77:1. 30. 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. 31. 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. 32. Fukuda K, Mori M, Uchiyama M, et al. Prognostic significance of progesterone receptor immunohistochemistry in endometrial carcinoma. Gynecol Oncol 1998; 69:220. Approach to adjuvant treatment of endometrial cancer - UpToDate 3/17/17, 10:03 AM https://www.uptodate.com/contents/approach-to-adjuvant-treatment-of-endometrial-cancer/print?source=see_link Page 8 of 11 33. 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. 34. Larson DM, Berg R, Shaw G, Krawisz BR. Prognostic significance of DNA ploidy in endometrial cancer. Gynecol Oncol 1999; 74:356. 35. 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. 36. 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. 37. Black D, Soslow RA, Levine DA, et al. Clinicopathologic significance of defective DNA mismatch repair in endometrial carcinoma. J Clin Oncol 2006; 24:1745. 38. 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. 39. 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. 40. Myers AP. New strategies in endometrial cancer: targeting the PI3K/mTOR pathway--the devil is in the details. Clin Cancer Res 2013; 19:5264. 41. 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. 42. 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. Topic 16742 Version 13.0 Approach to adjuvant treatment of endometrial cancer - UpToDate 3/17/17, 10:03 AM https://www.uptodate.com/contents/approach-to-adjuvant-treatment-of-endometrial-cancer/print?source=see_link Page 9 of 11 GRAPHICS Staging uterine carcinoma* (TNM and International Federation of Gynecology and Obstetrics [FIGO]) Primary tumor (T) (surgical-pathologic findings) TNM categories FIGO stages Definition TX Primary tumor cannot be assessed T0 No evidence of primary tumor Tis Carcinoma in situ (preinvasive carcinoma) T1 I Tumor confined to corpus uteri T1a IA Tumor limited to endometrium or invades less than one-half of the myometrium T1b IB Tumor invades one-half or more of the myometrium T2 II Tumor invades stromal connective tissue of the cervix but does not extend beyond uterus T3a IIIA Tumor involves serosa and/or adnexa (direct extension or metastasis) T3b IIIB Vaginal involvement (direct extension or metastasis) or parametrial involvement T4 IVA Tumor invades bladder mucosa and/or bowel mucosa (bullous edema is not sufficient to classify a tumor as T4) Regional lymph nodes (N) TNM categories FIGO stages Definition NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 IIIC1 Regional lymph node metastasis to pelvic lymph nodes N2 IIIC2 Regional lymph node metastasis to para-aortic lymph nodes, with or without positive pelvic lymph nodes Distant metastasis (M) TNM categories FIGO stages Definition M0 No distant metastasis M1 IVB Distant metastasis (includes metastasis to inguinal lymph nodes intraperitoneal disease, or lung, liver, or bone. It excludes metastasis to para-aortic lymph nodes, vagina, pelvic serosa, or adnexa.) Anatomic stage/prognostic groups Carcinomas* Stage 0 Tis N0 M0 Stage I T1 N0 M0 ¶ Δ ¶ Approach to adjuvant treatment of endometrial cancer - UpToDate 3/17/17, 10:03 AM https://www.uptodate.com/contents/approach-to-adjuvant-treatment-of-endometrial-cancer/print?source=see_link Page 10 of 11 Stage IA T1a N0 M0 Stage IB T1b N0 M0 Stage II T2 N0 M0 Stage III T3 N0 M0 Stage IIIA T3a N0 M0 Stage IIIB T3b N0 M0 Stage IIIC1 T1-T3 N1 M0 Stage IIIC2 T1-T3 N2 M0 Stage IVA T4 Any N M0 Stage IVB Any T Any N M1 NOTE: cTNM is the clinical classification, pTNM is the pathologic classification. * Carcinosarcomas should be staged as carcinoma. ¶ FIGO no longer includes Stage 0 (Tis). Δ Endocervical glandular involvement only should be considered as Stage I and not as Stage II. Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer New York, Inc. Graphic 51307 Version 14.0 Approach to adjuvant treatment of endometrial cancer - UpToDate 3/17/17, 10:03 AM https://www.uptodate.com/contents/approach-to-adjuvant-treatment-of-endometrial-cancer/print?source=see_link Page 11 of 11 Contributor Disclosures Steven C Plaxe, MD Grant/Research/Clinical Trial Support: Tesaro, Milennium, Pfizer, Astra-Zeneca, Pharma Mar, Bind, Janssen, Novartism, Incyte, Azaya [oncology (various study drugs)]. Arno J Mundt, MD Nothing to disclose Barbara Goff, MD Consultant/Advisory Boards: Roche Diagnostics [Biomarkers for ovarian cancer (HE4)]. Employment (Spouse): Lilly [General oncology (Gemcitabine, pemetrexed)] - No relevant conflict on topics. Don S Dizon, MD, FACP Consultant/Advisory Boards: Pfizer [Chemotherapy (Biosimilars)]. Sadhna R Vora, MD Nothing to disclose Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
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