Construction of the Prognostic Nomogram and Treatment Recommendation in Patients with Mixed Endometrial Carcinoma Treated with Hysterectomy

Overview

Journal Biomol Biomed

Specialties Biochemistry
General Medicine

Date 2024 Jul 9

PMID 38980685

Authors

Luyao Kang

Gaili Ji

Nan Zhang

Jie Meng

Duan Liu

Hongyu Li

Affiliations

Soon will be listed here.

Abstract

Mixed endometrial carcinomas (MECs) account for approximately 3%-10% of all endometrial carcinomas (ECs). These are defined as a combination of two or more distinct histologic subtypes, with at least one being a type II tumor that constitutes at least 5% of the overall tumor. However, the associated prognostic factors and treatment of MECs remain unclear. The study aimed to identify the independent prognostic factors of MEC patients treated with hysterectomy and to explore the optimal treatment modalities for overall survival (OS) and cancer-specific survival (CSS). Using the Surveillance, Epidemiology, and End Results (SEER) database, a total of 12,848 MEC patients treated with hysterectomy were screened. Independent prognostic factors were identified by Cox regression analysis and used to construct the nomogram. The concordance indices (C-indices) of OS and CSS were 0.807 and 0.834 in the training set. Validation of the nomogram revealed that the receiver operating curve (ROC) maintained good discrimination, the decision curve analysis (DCA) had a high net benefit rate, and the calibration curves showed high consistency. Patients were grouped by the nomogram formula and the number of positive regional lymph nodes (NPR-Lymph node) to evaluate the therapeutic outcomes of chemotherapy, radiotherapy, neoadjuvant treatment, and lymph node operation. Survival analysis revealed that chemotherapy could improve the prognosis for OS and CSS in the high-risk group and in the group with NPR-Lymph node counts above 1 (P < 0.05). Radiotherapy was associated with better OS and CSS in the intermediate-risk and high-risk groups, and in the group with NPR-Lymph node counts above 0 (P < 0.05). Lymphadenectomy was found to prolong OS and CSS in the high-risk group (P < 0.05), while neoadjuvant treatment did not prolong OS and CSS in any group. Thus, in this study, the nomogram for MEC patients treated with hysterectomy was successfully built and validated which could effectively predict the prognosis and identify at-risk population to guide clinical decision making. The NPR-Lymph node was identified as a potentially strong prognostic indicator with good clinical value.

References

Coenegrachts L, Garcia-Dios D, Depreeuw J, Santacana M, Gatius S, Zikan M . Mutation profile and clinical outcome of mixed endometrioid-serous endometrial carcinomas are different from that of pure endometrioid or serous carcinomas. Virchows Arch. 2015; 466(4):415-22. DOI: 10.1007/s00428-015-1728-5. View

Rauh-Hain J, Growdon W, Schorge J, Goodman A, Boruta D, McCann C . Prognostic determinants in patients with stage IIIC and IV uterine papillary serous carcinoma. Gynecol Oncol. 2010; 119(2):299-304. DOI: 10.1016/j.ygyno.2010.07.010. View

Garg K, Soslow R . Strategies for distinguishing low-grade endometrioid and serous carcinomas of endometrium. Adv Anat Pathol. 2011; 19(1):1-10. DOI: 10.1097/PAP.0b013e318234ab36. View

Rabban J, Gilks C, Malpica A, Matias-Guiu X, Mittal K, Mutter G . Issues in the Differential Diagnosis of Uterine Low-grade Endometrioid Carcinoma, Including Mixed Endometrial Carcinomas: Recommendations from the International Society of Gynecological Pathologists. Int J Gynecol Pathol. 2018; 38 Suppl 1:S25-S39. PMC: 6296831. DOI: 10.1097/PGP.0000000000000512. View

Kommoss S, McConechy M, Leung S, Bunz A, Magrill J, Britton H . Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series. Ann Oncol. 2018; 29(5):1180-1188. DOI: 10.1093/annonc/mdy058. View

Abu-Rustum N, Yashar C, Arend R, Barber E, Bradley K, Brooks R . Uterine Neoplasms, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2023; 21(2):181-209. DOI: 10.6004/jnccn.2023.0006. View

Yang Y, Wu S, Bao W . Molecular subtypes of endometrial cancer: Implications for adjuvant treatment strategies. Int J Gynaecol Obstet. 2023; 164(2):436-459. DOI: 10.1002/ijgo.14969. View

Uccella S, Falcone F, Greggi S, Fanfani F, De Iaco P, Corrado G . Survival in clinical stage I endometrial cancer with single vs. multiple positive pelvic nodes: results of a multi-institutional Italian study. J Gynecol Oncol. 2018; 29(6):e100. PMC: 6189435. DOI: 10.3802/jgo.2018.29.e100. View

Bokhman J . Two pathogenetic types of endometrial carcinoma. Gynecol Oncol. 1983; 15(1):10-7. DOI: 10.1016/0090-8258(83)90111-7. View

10.

Fader A, Starks D, Gehrig P, Secord A, Frasure H, OMalley D . An updated clinicopathologic study of early-stage uterine papillary serous carcinoma (UPSC). Gynecol Oncol. 2009; 115(2):244-8. DOI: 10.1016/j.ygyno.2009.07.030. View

11.

Berek J, Matias-Guiu X, Creutzberg C, Fotopoulou C, Gaffney D, Kehoe S . FIGO staging of endometrial cancer: 2023. Int J Gynaecol Obstet. 2023; 162(2):383-394. DOI: 10.1002/ijgo.14923. View

12.

Reid-Nicholson M, Iyengar P, Hummer A, Linkov I, Asher M, Soslow R . Immunophenotypic diversity of endometrial adenocarcinomas: implications for differential diagnosis. Mod Pathol. 2006; 19(8):1091-100. DOI: 10.1038/modpathol.3800620. View

13.

Zheng Y, Jiang P, Tu Y, Huang Y, Wang J, Gou S . Incidence, risk factors, and a prognostic nomogram for distant metastasis in endometrial cancer: A SEER-based study. Int J Gynaecol Obstet. 2023; 165(2):655-665. DOI: 10.1002/ijgo.15264. View

14.

Kobel M, Meng B, Hoang L, Almadani N, Li X, Soslow R . Molecular Analysis of Mixed Endometrial Carcinomas Shows Clonality in Most Cases. Am J Surg Pathol. 2015; 40(2):166-180. PMC: 5029122. DOI: 10.1097/PAS.0000000000000536. View

15.

Blanche P, Dartigues J, Jacqmin-Gadda H . Estimating and comparing time-dependent areas under receiver operating characteristic curves for censored event times with competing risks. Stat Med. 2013; 32(30):5381-97. DOI: 10.1002/sim.5958. View

16.

Murali R, Soslow R, Weigelt B . Classification of endometrial carcinoma: more than two types. Lancet Oncol. 2014; 15(7):e268-78. DOI: 10.1016/S1470-2045(13)70591-6. View

17.

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

18.

Quddus M, Sung C, Zhang C, Lawrence W . Minor serous and clear cell components adversely affect prognosis in ''mixed-type'' endometrial carcinomas: a clinicopathologic study of 36 stage-I cases. Reprod Sci. 2010; 17(7):673-8. DOI: 10.1177/1933719110368433. View

19.

Rossi E, Bizzarro T, Monterossi G, Inzani F, Fanfani F, Scambia G . Clinicopathological analysis of mixed endometrial carcinomas: clinical relevance of different neoplastic components. Hum Pathol. 2017; 62:99-107. DOI: 10.1016/j.humpath.2016.12.015. View

20.

Altay A, Toptas T, Dogan S, Simsek T, Pestereli E . Analysis of Metastatic Regional Lymph Node Locations and Predictors of Para-aortic Lymph Node Involvement in Endometrial Cancer Patients at Risk for Lymphatic Dissemination. Int J Gynecol Cancer. 2015; 25(4):657-64. DOI: 10.1097/IGC.0000000000000392. View