{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:31:38Z","timestamp":1787319098734,"version":"build-2736575974"},"reference-count":32,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: To develop a nomogram for predicting tumor aggressiveness and the presence of lymphovascular space involvement (LVSI) in patients with endometrial cancer (EC) using preoperative MRI and pathology\u2013laboratory data. Methods: This IRB-approved, retrospective, multicenter study included 245 patients with histologically confirmed EC who underwent preoperative MRI and surgery at participating institutions between January 2020 and December 2024. Tumor type and grade, both from preoperative biopsy and surgical specimens, as well as preoperative CA125 and HE4 levels, were retrieved from institutional databases. A preoperative MRI was used to assess tumor morphology (polypoid vs. infiltrative), maximum diameter, presence and depth (&lt; or &gt;50%) of myometrial invasion, cervical stromal invasion (yes\/no), and minimal tumor-to-serosa distance. The EC-to-uterus volume ratio was also calculated. Results: Among the 245 patients, 27% demonstrated substantial LVSI, and 35% were classified as aggressive on final histopathology. Multivariate analysis identified independent MRI predictors of LVSI, including cervical stromal invasion (OR = 9.06; p = 0.0002), tumor infiltration depth (OR = 2.09; p = 0.0391), and minimal tumor-to-serosa distance (OR = 0.81; p = 0.0028). The LVSI prediction model yielded an AUC of 0.834, with an overall accuracy of 78.4%, specificity of 92.2%, and sensitivity of 43.1%. For tumor aggressiveness prediction, significant predictors included biopsy grade (OR = 8.92; p &lt; 0.0001), histological subtype (OR = 12.02; p = 0.0021), and MRI-detected serosal involvement (OR = 14.39; p = 0.0268). This model achieved an AUC of 0.932, with an accuracy of 87.0%, sensitivity of 79.8%, and specificity of 91.2%. Both models showed excellent calibration (Hosmer\u2013Lemeshow p &gt; 0.86). Conclusions: The integration of MRI-derived morphological and quantitative features with clinical and histopathological data allows for effective preoperative risk stratification in endometrial cancer. The two nomograms developed for predicting LVSI and tumor aggressiveness demonstrated high diagnostic performance and may support individualized surgical planning and decision-making regarding adjuvant therapy. These models are practical, reproducible, and easily applicable in standard clinical settings without the need for radiomics software, representing a step toward more personalized gynecologic oncology.<\/jats:p>","DOI":"10.3390\/jcm14113914","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T11:40:32Z","timestamp":1748864432000},"page":"3914","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A Nomogram for Preoperative Prediction of Tumor Aggressiveness and Lymphovascular Space Involvement in Patients with Endometrial Cancer"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3465-0151","authenticated-orcid":false,"given":"Riccardo","family":"Valletta","sequence":"first","affiliation":[{"name":"Department of Radiology, Hospital of Bolzano (SABES-ASDAA), Teaching Hospital of Paracelsius Medical University (PMU), 39100 Bolzano-Bozen, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9926-760X","authenticated-orcid":false,"given":"Giacomo","family":"Avesani","sequence":"additional","affiliation":[{"name":"Department of Imaging and Radiotherapy, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Vingiani","sequence":"additional","affiliation":[{"name":"Department of Radiology, Hospital of Bolzano (SABES-ASDAA), Teaching Hospital of Paracelsius Medical University (PMU), 39100 Bolzano-Bozen, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernardo","family":"Proner","sequence":"additional","affiliation":[{"name":"Department of Radiology, Hospital of Bolzano (SABES-ASDAA), Teaching Hospital of Paracelsius Medical University (PMU), 39100 Bolzano-Bozen, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Steinkasserer","sequence":"additional","affiliation":[{"name":"Department of Ginecology, Hospital of Bolzano (SABES-ASDAA), Teaching Hospital of Paracelsius Medical University (PMU), 39100 Bolzano-Bozen, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Notaro","sequence":"additional","affiliation":[{"name":"Department of Ginecology, Hospital of Bolzano (SABES-ASDAA), Teaching Hospital of Paracelsius Medical University (PMU), 39100 Bolzano-Bozen, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Vanzo","sequence":"additional","affiliation":[{"name":"Department of Ginecology, Hospital of Bolzano (SABES-ASDAA), Teaching Hospital of Paracelsius Medical University (PMU), 39100 Bolzano-Bozen, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Negri","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hospital of Bolzano (SABES-ASDAA), Teaching Hospital of Paracelsius Medical University (PMU), 39100 Bolzano-Bozen, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1633-186X","authenticated-orcid":false,"given":"Caterina","family":"Vercelli","sequence":"additional","affiliation":[{"name":"Department of Health Sciences (DISSAL), University of Genoa, 16126 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4477-8944","authenticated-orcid":false,"given":"Matteo","family":"Bonatti","sequence":"additional","affiliation":[{"name":"Department of Radiology, Hospital of Bolzano (SABES-ASDAA), Teaching Hospital of Paracelsius Medical University (PMU), 39100 Bolzano-Bozen, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3322\/caac.21262","article-title":"Global cancer statistics, 2012","volume":"65","author":"Torre","year":"2015","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21551","article-title":"Cancer statistics, 2019","volume":"69","author":"Siegel","year":"2019","journal-title":"CA Cancer J. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1002\/ijgo.14923","article-title":"FIGO staging of endometrial cancer: 2023","volume":"162","author":"Berek","year":"2023","journal-title":"Int. J. Gynecol. Obstet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.diii.2018.01.010","article-title":"Preoperative MR imaging for ESMO-ESGO-ESTRO classification of endometrial cancer","volume":"99","author":"Lavaud","year":"2018","journal-title":"Diagn. Interv. Imaging"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Wang, J.J., Zhang, X.H., Guo, X.H., Ying, Y., Wang, X., Luan, Z.H., Lv, W.Q., and Wang, P.F. (2024). Prediction of Lymphovascular Space Invision in Endometrial Cancer based on Multi-parameter MRI Radiomics Model. Curr. Med. Imaging Former. Curr. Med. Imaging Rev., 20.","DOI":"10.2174\/0115734056266366231219111246"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"37","DOI":"10.4274\/tjod.galenos.2024.92597","article-title":"A novel predictive model of lymphovascular space invasion in early-stage endometrial cancer","volume":"21","author":"Sucu","year":"2024","journal-title":"J. Turk. Soc. Obstet. Gynecol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Qin, Z., Wang, Y., Chen, Y., Zheng, A., and Han, L. (2024). Evaluation of prognostic significance of lymphovascular space invasion in early stage endometrial cancer: A systematic review and meta-analysis. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1286221"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ejrad.2018.04.008","article-title":"Prediction of histological grade of endometrial cancer by means of MRI","volume":"103","author":"Bonatti","year":"2018","journal-title":"Eur. J. Radiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.ejrad.2014.11.010","article-title":"MRI for local staging of endometrial carcinoma: Is endovenous contrast medium administration still needed?","volume":"84","author":"Bonatti","year":"2015","journal-title":"Eur. J. Radiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e240084","DOI":"10.1148\/rg.240084","article-title":"RadioGraphics Update: 2023 FIGO Staging System for Endometrial Cancer","volume":"44","author":"Avesani","year":"2024","journal-title":"RadioGraphics"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e574","DOI":"10.1016\/j.crad.2023.04.005","article-title":"Endometrioid adenocarcinoma: Combined multiparametric MRI and tumour marker HE4 to evaluate tumour grade and lymphovascular space invasion","volume":"78","author":"Yue","year":"2023","journal-title":"Clin. Radiol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wang, J., Xu, P., Yang, X., Yu, Q., Xu, X., Zou, G., and Zhang, X. (2021). Association of Myometrial Invasion With Lymphovascular Space Invasion, Lymph Node Metastasis, Recurrence, and Overall Survival in Endometrial Cancer: A Meta-Analysis of 79 Studies With 68,870 Patients. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.762329"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.tjog.2023.07.004","article-title":"Effect of coexisting adenomyosis on tumour characteristics and prognosis of endometrial cancer: A systematic review and meta-analysis","volume":"62","author":"Wang","year":"2023","journal-title":"Taiwan. J. Obstet. Gynecol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Shawn LyBarger, K., Miller, H.A., and Frieboes, H.B. (2022). CA125 as a predictor of endometrial cancer lymphovascular space invasion and lymph node metastasis for risk stratification in the preoperative setting. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-22026-1"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"789","DOI":"10.2147\/TCRM.S372371","article-title":"Assessing Metabolic Risk Factors for LVSI in Endometrial Cancer: A Cross-Sectional Study","volume":"18","author":"Lin","year":"2022","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e11","DOI":"10.3802\/jgo.2017.28.e11","article-title":"Preoperative CA125 and fibrinogen in patients with endometrial cancer: A risk model for predicting lymphovascular space invasion","volume":"28","author":"Zhou","year":"2017","journal-title":"J. Gynecol. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Petrila, O., Nistor, I., Romedea, N.S., Negru, D., and Scripcariu, V. (2024). Can the ADC Value Be Used as an Imaging \u201cBiopsy\u201d in Endometrial Cancer?. Diagnostics, 14.","DOI":"10.3390\/diagnostics14030325"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Celli, V., Guerreri, M., Pernazza, A., Cuccu, I., Palaia, I., Tomao, F., Di Donato, V., Pricolo, P., Ercolani, G., and Ciulla, S. (2022). MRI- and Histologic-Molecular-Based Radio-Genomics Nomogram for Preoperative Assessment of Risk Classes in Endometrial Cancer. Cancers, 14.","DOI":"10.3390\/cancers14235881"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1136\/ijgc-2020-002230","article-title":"ESGO\/ESTRO\/ESP guidelines for the management of patients with endometrial carcinoma","volume":"31","author":"Concin","year":"2021","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.ygyno.2019.09.016","article-title":"LVSI positive and NX in early endometrial cancer: Surgical restaging (and no further treatment if N0), or adjuvant ERT?","volume":"156","author":"Harris","year":"2020","journal-title":"Gynecol. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.ygyno.2011.09.017","article-title":"Lymphovascular space invasion is an independent risk factor for nodal disease and poor outcomes in endometrioid endometrial cancer","volume":"124","author":"Guntupalli","year":"2012","journal-title":"Gynecol. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1016\/j.ejca.2015.05.015","article-title":"Substantial lymph-vascular space invasion (LVSI) is a significant risk factor for recurrence in endometrial cancer\u2014A pooled analysis of PORTEC 1 and 2 trials","volume":"51","author":"Bosse","year":"2015","journal-title":"Eur. J. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Kumar, S., Bandyopadhyay, S., Semaan, A., Shah, J.P., Mahdi, H., Morris, R., Munkarah, A., and Ali-Fehmi, R. (2011). The Role of Frozen Section in Surgical Staging of Low Risk Endometrial Cancer. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0021912"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1097\/IGC.0000000000000145","article-title":"Intraoperative Frozen Section Risk Assessment Accurately Tailors the Surgical Staging in Patients Affected by Early-Stage Endometrial Cancer","volume":"24","author":"Sala","year":"2014","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1002\/jmri.27142","article-title":"Multiparametric MRI-Based Radiomics Nomogram for Predicting Lymphovascular Space Invasion in Endometrial Carcinoma","volume":"52","author":"Luo","year":"2020","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Wang, J., Li, X., Yang, X., and Wang, J. (2022). Development and Validation of a Nomogram Based on Metabolic Risk Score for Assessing Lymphovascular Space Invasion in Patients with Endometrial Cancer. Int. J. Environ. Res. Public. Health, 19.","DOI":"10.3390\/ijerph192315654"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2828","DOI":"10.7150\/ijms.60718","article-title":"Prediction of lymphovascular space invasion in patients with endometrial cancer","volume":"18","author":"Kim","year":"2021","journal-title":"Int. J. Med. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1097\/PGP.0000000000000596","article-title":"Is It Possible to Develop a Prediction Model for Lymphovascular Space Invasion in Endometrioid Endometrial Cancer?","volume":"39","author":"Meydanli","year":"2020","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ma, C., Zhao, Y., Song, Q., Meng, X., Xu, Q., Tian, S., Chen, L., Wang, N., Song, Q., and Lin, L. (2023). Multi-parametric MRI-based radiomics for preoperative prediction of multiple biological characteristics in endometrial cancer. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1280022"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Rafiee, A., and Mohammadizadeh, F. (2023). Association of Lymphovascular Space Invasion (LVSI) with Histological Tumor Grade and Myometrial Invasion in Endometrial Carcinoma: A Review Study. Adv. Biomed. Res., 12.","DOI":"10.4103\/abr.abr_52_23"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Buechi, C.A., Siegenthaler, F., Sahli, L., Papadia, A., Saner, F.A.M., Mohr, S., Rau, T.T., Solass, W., Imboden, S., and Mueller, M.D. (2023). Real-World Data Assessing the Impact of Lymphovascular Space Invasion on the Diagnostic Performance of Sentinel Lymph Node Mapping in Endometrial Cancer. Cancers, 16.","DOI":"10.3390\/cancers16010067"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/11\/3914\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:46:16Z","timestamp":1760031976000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/11\/3914"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,2]]},"references-count":32,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["jcm14113914"],"URL":"https:\/\/doi.org\/10.3390\/jcm14113914","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,2]]}}}