ONCOLOGY Comparison of the prognostic significance of uterine factors and nodal status for endometrial cancer Nicanor I. Barrena Medel, MD; Thomas J. Herzog, MD; Israel Deutsch, MD; William M. Burke, MD; Xuming Sun, MS; Sharyn N. Lewin, MD; Jason D. Wright, MD OBJECTIVE: We examined the prognostic significance of uterine risk factors (RF) compared to nodal metastases in endometrial cancer. STUDY DESIGN: Women with stage I–IIIC endometrioid cancer were stratified based on the presence of positive or negative lymph nodes. Each patient was characterized by the number of RF present: myoinva- sion 50%, cervical stromal involvement, and grade 3 histology. RESULTS: A total of 26,967 women were identified. In a multivariable model, uterine RF strongly influenced survival but nodal disease was a more important negative prognostic factor. Five-year overall survival was 68% (95% confidence interval [CI], 63–72%) for group 1 (node positive/no RF) vs 69% (95% CI, 66 –72%) for group 5 (node negative/ multiple RF). Five–year survival was lower for node–positive patients with RF (58%; 95% CI, 54 – 61%) than node–positive patients without RF (68%; 95% CI, 63–72%). CONCLUSION: Uterine RF strongly influenced survival both in the pres- ence and absence of nodal metastasis. Key words: endometrial cancer, lymph nodes, lymphadenectomy, myometrial invasion, uterine cancer Cite this article as: Barrena Medel NI, Herzog TJ, Deutsch I, et al. Comparison of the prognostic significance of uterine factors and nodal status for endometrial cancer. Am J Obstet Gynecol 2011;204:248.e1-7. E ndometrial cancer is the most com- mon gynecologic malignancy. In 2010, it is estimated that 42,160 women in the United States were diagnosed with the disease. 1 While the vast majority of women with endometrial cancer are di- agnosed with early-stage tumors that are associated with an excellent prognosis, a subgroup of women have more aggres- sive neoplasms and are at increased risk of relapse and death. A number of local uterine risk factors (RF) including poor tumor differentiation, deep myometrial invasion, lymphvascular space invasion (LVSI), and cervical stromal involve- ment have been linked with decreased survival. 2-9 Metastasis to the regional lymph nodes (LN) is one of the most important predictors of survival for endometrial cancer. 10-13 In 1 series, 5-year disease- specific survival in women with nodal metastases was 42%. 12 The association between uterine RF and LN metastasis has been well established. The Gyneco- logic Oncology Group’s surgical pathol- ogy study of endometrial cancer found that uterine RF were strong predictors of nodal metastasis. The risk of nodal me- tastases was 25% in women with deep myometrial invasion compared to 5% in women with superficially invasive tu- mor. Likewise, patients with poorly dif- ferentiated tumors were 6 times more likely to have nodal disease than well-dif- ferentiated tumors, while the presence of LVSI increased the risk of nodal disease nearly 4-fold. 3 In light of the patterns of spread of endometrial cancer and the importance of nodal disease on survival, it has been hypothesized that the poor prognosis for women with early-stage tumors with uterine RF is most likely due to occult nodal disease at the time of presentation. 2 However, a growing body of evidence suggests that uterine RF may negatively impact survival independently of nodal metastasis. 4,5,14 The independent effect of uterine RF has been shown in women with early-stage disease with pathologi- cally negative nodes as well as in women with advanced-stage disease in which uterine RF continue to negatively influ- ence survival even after controlling for extrauterine disease. 13 The objective of our study was to estimate the influence of uterine RF on survival for women with endometrial cancer. Specifically, we compared the prognostic significance of uterine RF and nodal metastases and de- termined the independent effects of each on outcome. MATERIALS AND METHODS The National Cancer Institute’s Surveil- lance, Epidemiology, and End Results (SEER) database was utilized. SEER is a population-based cancer registry that in- cludes approximately 26% of the US population. 15 SEER is composed of a From the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology (Drs Barrena Medel, Herzog, Burke, Lewin, and Wright and Ms Sun), and the Department of Radiation Oncology (Dr Deutsch), Columbia University Collage of Physicians and Surgeons, and Herbert Irving Comprehensive Cancer Center (Drs Herzog, Deutsch, Burke, Lewin, and Wright), New York, NY. Presented at the Annual Meeting on Women’s Cancer of the Society of Gynecologic Oncologists, San Francisco, CA, March 14-17, 2010. Received July 9, 2010; revised Sept. 7, 2010; accepted Oct. 13, 2010. Reprints: Jason D. Wright, MD, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, 161 Fort Washington Ave., 8th Floor, New York, NY 10032. jw2459@columbia.edu. 0002-9378/$36.00 © 2011 Mosby, Inc. All rights reserved. doi: 10.1016/j.ajog.2010.10.903 Research www. AJOG.org 248.e1 American Journal of Obstetrics & Gynecology MARCH 2011