Prognostic potential of tumor lesions of the lower uterine segment in early endometrioid cancer of the uterine body

In modern clinical practice, when deciding on the amount of adjuvant therapy for cancer of the uterine body (UBC), such a factor as a tumor lesion of the lower uterine segment (LUS) is not considered, although a number of studies indicate its possible connection with a more aggressive course of the disease.
Purpose of the study. To study the relationship between tumor involvement of the LUS and traditional clinical and morphological prognostic factors, and the impact of this parameter on the treatment outcomes of early endometrial cancer.
Patients and methods. The study included 506 patients with stage I endometrioid UBC according to the classification of the International Federation of Gynecologists and Obstetricians (FIGO) who underwent surgical or combined treatment at the A. Tsyb Medical Radiological Research Center – Branch of the National Medical Research Radiological Center (Obninsk, Russian Federation) in 2002–2024. The median follow-up was 81.1 months. The patients were divided into two groups depending on the presence or absence of a tumor lesion of the LUS according to the histological conclusion: respectively Group 1–175 (34.6 %) patients, group 2–331 (65.4 %) patients.
Results. LUS involvement was found in 34.6 % of patients. It was found that these patients more often had factors such as lymphovascular invasion (LVI) (p < 0.001) and deep invasion into the myometrium (p < 0.001). Overall, LUS involvement was recorded in 23 % of patients without traditional unfavorable prognostic factors and in 50 % of patients with these factors (p < 0.001). At the same time, more common forms of the disease affecting the pathomorphological stage were more frequently detected in the group of patients with LUS involvement – 20.0 % versus 5.1 % in the group without LUS involvement (p < 0.001). Thus, in cases of LUS involvement, the risk of detecting a more common tumor process after histological examination increases 3.9 times compared to cases without LUS involvement. Survival analysis at the current follow-up period showed a statistically significant decrease in overall and five-year survival rates in patients with stage I UBC with LUS involvement – 87.9 % and 75.3 ± 4.8 %, respectively, compared with 93.4 % and 93.1 ± 2.5 % without LUS involvement (with p = 0.044 and p < 0.001, respectively).
Conclusion. Tumor involvement of the LUS can be considered a potential diagnostic predictor for the detection of more common forms of stage I UBC and a prognostic indicator of an unfavorable outcome of endometrioid disease.

1. Malignant neoplasms in Russia in 2023 (morbidity and mortality). Edited by Kaprin AD, Starinsky VV, Shakhzadova AO. Мoscow: P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Radiology Research Centre of the Ministry of Health of the Russian Federation; 2024, 276 p. (In Russ.). Available at: https://oncology-association.ru/wp-content/uploads/2024/08/zis-2023-elektronnaya-versiya.pdf (accessed: 06.06.2025).

2. Hoffmann J, Exner M, Bremicker K, Grothoff M, Stumpp P, Stepan H. Comparison of the lower uterine segment in pregnant women with and without previous cesarean section in 3 T MRI. BMC Pregnancy Childbirth. 2019 May 8;19(1):160. https://doi.org/10.1186/s12884-019-2314-7

3. Savitsky AG, Abramchenko VV, Savitsky GA. The role of the lower segment in the birth process. Journal of Obstetrics and Women's Diseases. 2005;54(3):19–27. (In Russ.).

4. Miyoshi A, Kanao S, Naoi H, Otsuka H, Yokoi T. Investigation of the clinical features of lower uterine segment carcinoma: association with advanced stage disease and indication of poorer prognosis. Arch Gynecol Obstet. 2018 Jan;297(1):193–198. https://doi.org/10.1007/s00404-017-4576-5

5. Jacques SM, Qureshi F, Ramirez NC, Malviya VK, Lawrence WD. Tumors of the uterine isthmus: clinicopathologic features and immunohistochemical characterization of p53 expression and hormone receptors. Int J Gynecol Pathol. 1997 Jan;16(1):38–44. PMID: 8986531.

6. Mayr NA, Wen BC, Benda JA, Sorosky JI, Davis CS, Fuller RW, Hussey DH. Postoperative radiation therapy in clinical stage I endometrial cancer: corpus, cervical, and lower uterine segment involvement--patterns of failure. Radiology. 1995 Aug;196(2):323–328. https://doi.org/10.1148/radiology.196.2.7617840

7. Akdöner A, Kurt S, Yavuz O, Bayram E, Üresin M, Ulukuş EÇ. Effect of low uterine segment involvement on prognosis of early stage endometrial cancer. J Obstet Gynaecol Res. 2024 Jun;50(6):991–1001. https://doi.org/10.1111/jog.15933

8. Madom LM, Brown AK, Lui F, Moore RG, Granai CO, Disilvestro PA. Lower uterine segment involvement as a predictor for lymph node spread in endometrial carcinoma. Gynecol Oncol. 2007 Oct;107(1):75–78. https://doi.org/10.1016/j.ygyno.2007.05.026

9. Buhimschi CS, Buhimschi IA, Zhao G, Funai E, Peltecu G, Saade GR, Weiner CP. Biomechanical properties of the lower uterine segment above and below the reflection of the urinary bladder flap. Obstet Gynecol. 2007 Mar;109(3):691–700. https://doi.org/10.1097/01.aog.0000236448.61465.95

10. Erkaya S, Öz M, Topçu HO, Şirvan AL, Güngör T, Meydanli MM. Is lower uterine segment involvement a prognostic factor in endometrial cancer? Turk J Med Sci. 2017 Feb 27;47(1):300–306. https://doi.org/10.3906/sag-1602-137

11. Davidesko S, Meirovitz M, Shaco-Levy R, Yarza S, Samueli B, Kezerle Y, Kessous R. The significance of lower uterine segment involvement in endometrial cancer. Eur J Surg Oncol. 2024 Mar;50(3):108007. https://doi.org/10.1016/j.ejso.2024.108007

12. Akdöner A, Kurt S, Yavuz O, Bayram E, Üresin M, Ulukuş EÇ. Effect of low uterine segment involvement on prognosis of early stage endometrial cancer. J Obstet Gynaecol Res. 2024 Jun;50(6):991–1001. https://doi.org/10.1111/jog.15933

13. Pergialiotis V, Fanaki M, Panagiotopoulos M, Bramis K, Vlachos DE, Daskalakis G, et al. Survival outcomes of endometrial cancer patients with disease involving the lower uterine segment: A meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2025 Jan;304:70–76. https://doi.org/10.1016/j.ejogrb.2024.11.031

14. Clark LH, Gehrig PA, Bae-Jump V, Franasiak J, Ko EM. Does Lower Uterine Segment Involvement in Grade 3 Endometrial Cancer Impact Recurrence Patterns and Patient Outcomes? J Clin Gynecol Obstet. 2014;3(3):85–92. https://doi.org/10.14740/jcgo264w

15. Kogan L, Octeau D, Amajoud Z, Abitbol J, Laskov I, Ferenczy A, et al. Impact of lower uterine segment involvement in type II endometrial cancer and the unique mutational profile of serous tumors. Gynecol Oncol Rep. 2018 Mar 19;24:43–47. https://doi.org/10.1016/j.gore.2018.03.004

16. Brown AK, Madom L, Moore R, Granai CO, DiSilvestro P. The prognostic significance of lower uterine segment involvement in surgically staged endometrial cancer patients with negative nodes. Gynecol Oncol. 2007 Apr;105(1):55–58. https://doi.org/10.1016/j.ygyno.2006.10.058

17. Gemer O, Uriev L, Harkovsky T, Peled R, Ben-Dor D, Barak F, Segal S. Significance of lower uterine segment involvement in women with stage I endometrial adenocarcinoma. J Reprod Med. 2004 Sep;49(9):703-6. PMID: 15493559.

18. Cancer of the uterine body and uterine sarcomas. Сlinical recommendations. Moscow: Ministry of Health of Russia, 2024. (In Russ.). Available at: https://cr.minzdrav.gov.ru/preview-cr/460_4. Accessed: 19.05.2025.

19. WHO classification of tumours. Pathology and genetics of tumours of the breast and female genital organs. Lyon: International Agency for Research on Cancer, 2003.

20. Kurman RJ; International Agency for Research on Cancer; World Health Organization. WHO classification of tumours of female reproductive organs. Lyon: International Agency for Research on Cancer, 2014.

21. Höhn AK, Brambs CE, Hiller GGR, May D, Schmoeckel E, Horn LC. 2020 WHO Classification of Female Genital Tumors. Geburtshilfe Frauenheilkd. 2021 Oct;81(10):1145–1153. https://doi.org/10.1055/a-1545-4279

22. TNM classification of malignant tumours. Edited by Brierley JD, Gospodarowicz MK, Wittekind C. B. NJ: John Wiley & Sons, Inc., 2017.

23. Creasman W. Revised FIGO staging for carcinoma of the endometrium. Int J Gynaecol Obstet. 2009 May;105(2):109. https://doi.org/10.1016/j.ijgo.2009.02.010

24. Kizer NT, Gao F, Guntupalli S, Thaker PH, Powell MA, Goodfellow PJ, et al. Lower uterine segment involvement is associated with poor outcomes in early-stage endometrioid endometrial carcinoma. Ann Surg Oncol. 2011 May;18(5):1419–1424. https://doi.org/10.1245/s10434-010-1454-9

25. Aminimoghaddam S, Kamyabi G, Yarandi F, Zarei S. Investigating the Association of Lower Uterine Segment Involvement with Deep Myometrial Invasion in Endometrial Adenocarcinoma. 2022; 2(2) Journal of Obstetrics, Gynecology and Cancer Research. https://doi.org/10.5812/jogcr.10991

26. Oliver-Perez MR, Magriña J, Villalain-Gonzalez C, Jimenez-Lopez JS, Lopez-Gonzalez G, Barcena C, et al. Lymphovascular space invasion in endometrial carcinoma: Tumor size and location matter. Surg Oncol. 2021 Jun;37:101541. https://doi.org/10.1016/j.suronc.2021.101541

27. Lavie O, Uriev L, Gdalevich M, Barak F, Peer G, Auslender R, et al. The outcome of patients with stage I endometrial cancer involving the lower uterine segment. Int J Gynecol Cancer. 2008 Sep-Oct;18(5):1079–1083. https://doi.org/10.1111/j.1525-1438.2007.01150.x

28. Gemer O, Gdalevich M, Voldarsky M, Barak F, Ben Arie A, Schneider D, et al. Lower uterine segment involvement is associated with adverse outcome in patients with stage I endometroid endometrial cancer: results of a multicenter study. Eur J Surg Oncol. 2009 Aug;35(8):865–869. https://doi.org/10.1016/j.ejso.2008.10.007

29. Hachisuga T, Fukuda K, Iwasaka T, Hirakawa T, Kawarabayashi T, Tsuneyoshi M. Endometrioid adenocarcinomas of the uterine corpus in women younger than 50 years of age can be divided into two distinct clinical and pathologic entities based on anatomic location. Cancer. 2001 Nov 15;92(10):2578–2584. https://doi.org/10.1002/1097-0142(20011115)92:10<2578::aid-cncr1610>3.0.co;2-v

30. Dilek S, Dede M, Gezginç K, Yenen MC, Göktolga U, Ulutin HC, et al. Does the localisation of tumour at stage I endometrial endometrioid adenocarcinoma have an impact on invasion of the tumour and individualisation of the surgical procedure? Eur J Gynaecol Oncol. 2008;29(2):138–140.

31. Yamazaki H, Takeshita S, Todo Y, Matsumiya H, Shimada C, Minobe S, et al. Imaging-based definition of lower uterine segment carcinoma to improve the detection sensitivity of probable Lynch syndrome. Jpn J Clin Oncol. 2020 Mar 9;50(3):270–275. https://doi.org/10.1093/jjco/hyz162

32. Nougaret S, Horta M, Sala E, Lakhman Y, Thomassin-Naggara I, Kido A, et al. Endometrial Cancer MRI staging: Updated Guidelines of the European Society of Urogenital Radiology. Eur Radiol. 2019 Feb;29(2):792–805. https://doi.org/10.1007/s00330-018-5515-y

33. Nougaret S, Reinhold C, Alsharif SS, Addley H, Arceneau J, Molinari N, Guiu B, Sala E. Endometrial Cancer: Combined MR Volumetry and Diffusion-weighted Imaging for Assessment of Myometrial and Lymphovascular Invasion and Tumor Grade. Radiology. 2015 Sep;276(3):797–808. https://doi.org/10.1148/radiol.15141212