Practical guidance for assessing and reporting lymphovascular space invasion (LVSI) in endometrial carcinoma.

Lymphovascular space invasion (LVSI) is an important prognostic parameter in endometrial carcinoma (EC) and has gained increasing interest in recent years due to an expanding body of evidence of its independent prognostic value, especially when the presence of LVSI is quantified. A key strength of LVSI as a prognostic factor is that it can be detected on routine microscopic examination, without ancillary tests, and thus can be used in low-resource settings. A weakness, however, is the lack of uniformly applied criteria for assessment and quantification of LVSI, resulting in interobserver variation in diagnosis. This is confounded by artefacts and other morphological features that may mimic LVSI (commonly referred to as pseudo-LVSI). Despite these issues, multiple studies have shown that LVSI is strongly associated with lymph node (LN) metastasis and is an independent risk factor for LN recurrence and distant metastasis. Consequently, the presence of substantial/extensive LVSI has become an important consideration in formulating adjuvant treatment recommendations in patients with EC, and this has been incorporated in the recent International Federation of Gynecology and Obstetrics (FIGO) 2023 staging system. Herein, we review the current literature on LVSI in EC and discuss its role as a prognostic marker, the reproducibility of LVSI assessment and distinction between LVSI and its mimics. We provide illustrations of key diagnostic features and discuss the two-tiered (none/focal versus substantial) system of LVSI classification. This work is intended to provide guidance to practising pathologists and unify the approach towards LVSI assessment in EC.

2023 FIGO staging system for endometrial cancer: The evolution of the revolution.

INTRODUCTION: Embracing the complex and diverse nature of the heterogenous group of malignancies that are included under the umbrella of "endometrial cancer" (EC) to better align prognosis with treatment recommendations, requires a more comprehensive staging system. Our goal at the development of the new FIGO staging was to provide 1) high accuracy in the predictive prognosis for a patient with EC, which is the genuine purpose of a staging system, and 2) identification of distinct treatment relevant subgroups. Since the publication of the 2009 staging system by the International Federation of Gynecology and Obstetrics (FIGO) 14  years ago (1, 2), our understanding of the biology and natural history of EC has undergone a radical transformation. The TGCA results in 2013 (3), and the many validation reports published since then (4-9), have taught us that "EC" is composed of at least four distinct molecularly defined diseases. Strong histopathologic markers reflecting tumor biology such as lymph vascular space invasion (LVSI) were identified. Importantly, anatomical borders were shown to lose their prognostic relevance for EC patients in the presence of dominant tumor biology-markers such as molecular subtypes/LVSI (10, 11). This emphasizes the integration of these novel markers into a prognostic staging system that aims to be relevant to patients. The 2023 FIGO staging system for EC harmonizes and integrates old and new knowledge on anatomic, histopathologic, and molecular features (12). It requires a change in our perception of a staging system, from a traditional purely anatomical borders-based system to an integrated staging system integrating anatomical borders and tumor biology as pivotal prognostic factors for EC patients while providing important information for treatment decision making. Therefore, the 2023 FIGO staging system demonstrates the logical next step in the evolution of the revolution in a patient-centric staging approach. Below, we elucidate the rationale for the FIGO 2023 endometrial cancer staging system.

Prognostic significance of lymphovascular space invasion in early-stage low-grade endometrioid endometrial cancer: a fifteen-year retrospective Chinese cohort study.

OBJECTIVE: In 2016, the ESMO-ESGO-ESTRO consensus included LVSI (Lymph-vascular space invasion, LVSI) status as a risk stratification factor for stage I endometrioid endometrial cancer (EEC) patients and as one of the indications for adjuvant therapy. Furthermore, LVSI is included in the new FIGO staging of endometrial cancer (EC) in 2023. However, the data contribution of the Chinese population in this regard is limited. The present study aimed to further comfirm the influence of LVSI on the prognosis of early-stage low-grade EEC in a fifteen-year retrospective Chinese cohort study. METHODS: This retrospective analysis cohort included 702 EEC patients who underwent TAH/BSO surgery, total abdominal hysterectomy, bilateral salpingooophorectomy in Peking University People's Hospital from 2006 to 2020. Patients were stratified based on LVSI expression status as: LVSI negative group and LVSI positive group. Clinical outcome measures related to LVSI, assessed with a univariate and multivariate Cox proportional hazards regression model. RESULTS: 702 EEC patients with stage I and grade 1-2 were analyzed. 58 patients (8.3%) were LVSI-positive and 14 patients (2.0%) was relapse. Recurrence rates in LVSI-negative and LVSI-positive were 1.6% and 6.9%, respectively. 5-year disease-free survival (DFS) rate in LVSI-negative and LVSI-positive were 98.4% and 93.1%, respectively. These rates for 5-year overall (OS) survival in LVSI-negative were 98.9% while it was 94.8% in LVSI-positive. Multivariate analysis showed that LVSI is an independent risk factor for 5-year DFS (HR = 4.60, p = 0.010). LVSI has a similar result for 5-year OS(HR = 4.39, p = 0.028). CONCLUSIONS: LVSI is an independent predictor of relapse and poor prognosis in early-stage low-grade endometrioid endometrial cancer in the Chinese cohort.

New mechanisms and biomarkers of lymph node metastasis in cervical cancer: reflections from plasma proteomics.

OBJECTIVE: Lymph node metastasis (LNM) and lymphatic vasculature space infiltration (LVSI) in cervical cancer patients indicate a poor prognosis, but satisfactory methods for diagnosing these phenotypes are lacking. This study aimed to find new effective plasma biomarkers of LNM and LVSI as well as possible mechanisms underlying LNM and LVSI through data-independent acquisition (DIA) proteome sequencing. METHODS: A total of 20 cervical cancer plasma samples, including 7 LNM-/LVSI-(NC), 4 LNM-/LVSI + (LVSI) and 9 LNM + /LVSI + (LNM) samples from a cohort, were subjected to DIA to identify differentially expressed proteins (DEPs) for LVSI and LNM. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed for DEP functional annotation. Protein-protein interaction (PPI) and weighted gene coexpression network analysis (WGCNA) were used to detect new effective plasma biomarkers and possible mechanisms. RESULTS: A total of 79 DEPs were identified in the cohort. GO and KEGG analyses showed that DEPs were mainly enriched in the complement and coagulation pathway, lipid and atherosclerosis pathway, HIF-1 signal transduction pathway and phagosome and autophagy. WGCNA showed that the enrichment of the green module differed greatly between groups. Six interesting core DEPs (SPARC, HPX, VCAM1, TFRC, ERN1 and APMAP) were confirmed to be potential plasma diagnostic markers for LVSI and LNM in cervical cancer patients. CONCLUSION: Proteomic signatures developed in this study reflected the potential plasma diagnostic markers and new possible pathogenesis mechanisms in the LVSI and LNM of cervical cancer.

Influence of uterine manipulator use on the incidence of lymphovascular propagation in the treatment of endometrial cancer.

BACKGROUND: Endometrial cancers are among the epithelial malignancies of the lining of the uterine cavity. The invasion of carcinoma into the lymphovascular space (LVSI) is considered a risk factor for the course of the disease. MATERIAL AND METHODS: We evaluated 170 female patients. Our primary objective was to find any difference in the incidence of LVSI in female patients treated with and without an intrauterine manipulator. In addition, we analyzed the effect of the type of intrauterine manipulator used on the incidence of LVSI, tumor grading, myometrial invasion, and the method of obtaining primary histology with regard to the incidence of LVSI. RESULTS: Using a manipulator during surgery was not associated with LVSI (with a manipulator vs. without, 11.5 vs. 21.7%; OR 1.8; 95% CI 0.73-4.39; p = 0.199). However, the method used to obtain the primary histology had a statistically significant effect on the incidence of LVSI in our set (p-value = 0.011). CONCLUSIONS: In our study, we did not confirm the effect of a uterine manipulator on the possible increase of LVSI positive cases. The secondary analysis indicated a higher incidence of LVSI in the female patients diagnosed with curettage than in those who underwent hysteroscopy. Trail registration: Trail is registered in ClicincalTrails.gov with identifier: NCT05261165.

A multicenter noninferior randomized controlled study comparing the efficacy of laparoscopic versus abdominal radical hysterectomy for cervical cancer (stage IA1 with LVSI, IA2): study protocol of the LAUNCH 1 trial.

BACKGROUND: A retrospective study and a randomized controlled trial published in a high quality journal in late 2018 have shown that laparoscopic radical hysterectomy (RH) was associated with worse survival than abdominal RH among patients with early stage cervical cancer. Radical hysterectomy in cervical cancer has been a classic landmark surgery in gynecology, therefore this conclusion is pivotal. The current trial is designed to reconfirm whether there is a difference between laparoscopic RH and abdominal RH in cervical cancer (stage IA1 with LVSI, IA2) patient survival under stringent operation standards and consistent tumor-free technique. This paper reports the rationale, design, and implementation of the trial. METHODS: This is an investigator-initiated, prospective, randomized, open, blinded endpoint (PROBE) controlled trial. A total of 690 patients with stage IA1 (with intravascular), and IA2 cervical cancer will be enrolled over a period of three years. Patients are randomized (1:1) to either the laparoscopic RH or the abdominal RH group. Patients will then be followed-up for at least five years. The primary endpoint will be 5-year progression-free survival. Secondary endpoints will include 5-year overall survival rates, recurrence rates, operation time, intraoperative blood loss, surgery-related complications, and quality of life. DISCUSSION: The results of the trial will provide valuable evidence for guiding clinical decision of choosing appropriate treatment strategies for stage IA1 (LVSI) and stage IA2 cervical cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT04934982 , Registered on 22 June 2021).

Prognostic value of the 2018 FIGO staging system for cervical cancer.

OBJECTIVE: To compare the prognostic performance of the FIGO 2009 and FIGO 2018 staging systems for cervical cancer (CC) in regards to risk stratification, survival and treatment outcome. METHODS: A total of 4461 CC patients diagnosed in Denmark during 2005-2018 were identified through the Danish Gynaecological Cancer Database and restaged from the 2009 FIGO to the 2018 FIGO staging system. 5-year survival estimates were made for each group. Also, association between lymphovascular space invasion (LVSI) and lymph node metastasis (LNM) was assesed for tumors with a horizontal spread >7 mm and depth of invasion ≤5 mm. RESULTS: Overall, stage migration was observed in 41.4% of our cases due to the introduction of stage IIIC (20.1%), refined tumor size criteria within stage I (76.2%), and use of radiological findings to define stage IV (3.7%). 5-year overall survival increased for all stages except IA2, IIA2, IIIA and IIIB. Restaging of 2009 IB1 to 2018 FIGO resulted in significant stage allocations. Furthermore, an association between LVSI and LNM was observed in squamous cell carcinomas with a depth of invasion of 3-5 mm and a horizontal spread >7 mm (p = 0.03). CONCLUSION: The 2018 FIGO staging system provided improved discriminatory ability for stage I and IV. Grouping all patients with positive pelvic or paraortal lymph nodes to stage IIIC led to pronounced heterogenous survival rates within these stages. Lymph node assessment was proven imperative in FIGO 2018 IA2 squamous cell carcinomas with a depth of invasion of 3-5 mm, a horizontal spread >7 mm and LVSI.

Value of integrated PET-IVIM MRI in predicting lymphovascular space invasion in cervical cancer without lymphatic metastasis.

PURPOSE: To evaluate the contributory value of positron emission tomography (PET)-intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) in the prediction of lymphovascular space invasion (LVSI) in patients with cervical cancer without lymphatic metastasis. MATERIALS AND METHODS: A total of 90 patients with cervical cancer without signs of lymph node metastasis on PET/MRI were enrolled in this study. The tumours were classified into LVSI-positive (n = 25) and LVSI-negative (n = 65) groups according to postoperative pathology. The PET-derived parameters (SUVmax, SUVmean, metabolic tumour volume (MTV) and total lesion glycolysis (TLG)) and IVIM-derived parameters (ADCmean, ADCmin, Dmean, Dmin, f, D* and gross tumour volume (GTV)) between the two groups were evaluated using a Student's t test (Mann-Whitney U test for variables with a nonnormal distribution) and receiver operating characteristic (ROC) curves. The optimal combination of PET/MR parameters for predicting LVSI was investigated using univariate and multivariate logistic regression models and evaluated by ROC curves. The optimal cutoff threshold values corresponded to the maximal values of the Youden index. A control model was established using 1000 bootstrapped samples, for which the performance was validated using calibration curves and ROC curves. RESULTS: PET-derived parameters (SUVmax, SUVmean, MTV, TLG) and IVIM MRI-derived parameters (Dmin, ADCmin, GTV) were significantly different between patients with and without LVSI (P < 0.05). Logistic analyses showed that a combination of TLG and Dmin had the strongest predictive value for LVSI diagnosis (area under the curve (AUC), 0.861; sensitivity, 80.00; specificity, 86.15; P < 0.001). The optimal cutoff threshold values for Dmin and TLG were 0.58 × 10-3 mm2/s and 66.68 g/cm3, respectively. The verification model showed the combination of TLG and Dmin had the strongest predictive value, and its ROC curve and calibration curve showed good accuracy (AUC, 0.878) and consistency. CONCLUSIONS: The combination of TLG and Dmin may be the best indicator for predicting LVSI in cervical cancer without lymphatic metastasis.

Development and validation of a comprehensive clinical risk-scoring model for prediction of overall survival in patients with endometrioid endometrial carcinoma.

OBJECTIVE: To develop and validate a comprehensive overall survival (OS) risk-scoring model in women with endometrioid endometrial cancer (EC). METHODS: Patients with EC diagnosed from 2004 to 2013 were identified through the National Cancer Database (NCDB). Patients with known lymphovascular space invasion (LVSI) status who were treated surgically (with or without adjuvant therapy) were included. Cox proportional hazards analysis was used to identify prognostic factors for OS. This model was used to assign points based on hazard ratios for risk factors and a risk score was obtained. Recursive partitioning analysis (RPA) was used to categorize patients into risk groups. Results were internally validated in a cohort of patients from our institution (CCF cohort). Risk scores were calculated and assessed in a Cox regression model, and Harrell's c-index was calculated to assess model fit. RESULTS: Among 349,404 women with EEC during the study period, 42,107 fulfilled inclusion criteria. Factors associated with worse OS were age ≥ 60, African American race, Charlson-Deyo score 1 or 2+, higher grade, LVSI, tumor size ≥2 cm, and no lymphadenectomy performed. Six risk groups were identified (scores 0-30) and OS estimated for each risk group. Risk score per 1-point increase in HR were comparable between NCDB and CCF cohorts (HR 1.21 (1.20-1.22 p < 0.001 vs 1.18 (1.12-1.25), p < 0.001), and c-index 0.80 (0.79-0.81) vs. 0.77 (0.68-0.86). Similar analysis was done in stage IA and IB. Adjuvant therapy had a beneficial effect on survival in the majority of stage IB patients, but only one of the six risk groups in stage IA EC. CONCLUSIONS: We report a comprehensive validated OS risk-scoring model for patients with.

The role of semiquantitative evaluation of lympho-vascular space invasion in early stage cervical cancer patients.

OBJECTIVE: Lymph vascular space involvement (LVSI) is one of the most important prognostic factors in early stage cervical cancer. Its qualitative evaluation represents a milestone for patient risk stratification and treatment choice, but a semi-quantitative analysis of LVSI may offer a more truthful risk model, as already demonstrated for endometrial cancer. The present study aims to investigate the performances of a semi-quantitative evaluation of LVSI in terms of patient risk assessment. METHODS: In this retrospective study were enrolled patients underwent surgical treatment for early cervical cancer from January 2009 to October 2018. A semi-quantitative evaluation such as the "three-tiered approach" was used to classify the LVSI pathway: negative vs. focal vs. diffuse. RESULTS: Diffuse LVSI was found to be a risk factor for lymph node metastasis (OR: 9.844, p < 0.001), and parametrial involvement (OR: 5.566, p < 0.001). Lymph nodal recurrences were more frequent in diffuse LVSI group (LVSI negative vs. focal LVSI p = 0.369; LVSI negative vs. diffuse LVSI p = 0.002; Focal LVSI vs. diffuse LVSI p = 0.214); and so distant recurrences (LVSI negative vs. focal LVSI p = 0.623; LVSI negative vs. diffuse LVSI p = 0.002; Focal LVSI vs. diffuse LVSI p = 0.026). Patients with diffuse LVSI showed a worse disease-free survival (DFS) than patients with focal or absent involvement (DFS LVSI negative vs. focal LVSI p = 0.938; LVSI negative vs. diffuse LVSI p < 0.001; focal LVSI vs. diffuse LVSI p = 0.036). CONCLUSION: Semi-quantitative evaluation of LVSI may be useful to identify risk patients for shorter disease-free survival and lymphatic and distant recurrences in patients with early stage.

Prediction of lymphovascular space invasion in patients with endometrial cancer.

Objective: Predict the presence of lymphovascular space invasion (LVSI), using uterine factors such as tumor diameter (TD), grade, and depth of myometrial invasion (MMI). Develop a predictive model that could serve as a marker of LVSI in women with endometrial cancer (EC). Methods: Data from 888 patients with endometrioid EC who were treated between January 2009 and December 2018 were reviewed. The patients' data were retrieved from six institutions. We assessed the differences in the clinicopathological characteristics between patients with and without LVSI. We performed logistic regression analysis to determine which clinicopathological characteristics were the risk factors for positive LVSI status and to estimate the odds ratio (OR) for each covariate. Using the risk factors and OR identified through this process, we created a model that could predict LVSI and analyzed it further using receiver operating characteristic curve analysis. Results: In multivariate logistic regression analysis, tumor size (P = 0.027), percentage of MMI (P < 0.001), and presence of cervical stromal invasion (P = 0.002) were identified as the risk factors for LVSI. Based on the results of multivariate logistic regression analysis, we developed a simplified LVSI prediction model for clinical use. We defined the "LVSI index" as "TD×%MMI×tumor grade×cervical stromal involvement." The area under curve was 0.839 (95% CI= 0.809-0.869; sensitivity, 74.1%; specificity, 80.5%; negative predictive value, 47.3%; positive predictive value, 8.6%; P < 0.001), and the optimal cut-off value was 200. Conclusion: Using the modified risk index of LVSI, it is possible to predict the presence of LVSI in women with endometrioid endometrial cancer. Our prediction model may be an appropriate tool for integration into the clinical decision-making process when assessed either preoperatively or intraoperatively.

Factors predicting recurrence in patients with stage IA endometrioid endometrial cancer: what is the importance of LVSI?

PURPOSE: The aim of this study is to define the clinical and pathological prognostic factors for recurrence and to evaluate the recurrence patterns and adjuvant therapies used in this group of patients with stage IA endometrioid type endometrial cancer (FIGO 2009-International Federation of Gynecology and Obstetrics). METHODS: Among the patients with epithelial endometrial cancer operated between January 1993 and May 2013 in a single institution, 720 patients with stage IA endometrioid endometrial cancer were included. Patients with a tumor type of serous, clear cell, mucinous, undifferentiated, and mixed type and with a tumor containing sarcomatous component and the patients with a secondary primer cancer were excluded from the study. RESULTS: Lympho-vascular space invasion (LVSI) was present in 60 (8.3%) patients. Pelvic and para-aortic lymphadenectomy was performed in 266 (36.9%) patients. Median follow-up time was 48 months (range 3-240). Recurrence occurred in 23 (3.4%) patients and 6 (0.9%) died of disease. The median time-to recurrence (TTR) was 24 months (range 4-52 months) in the patients with recurrence. LVSI was associated with recurrence in the univariate analysis. Five-year disease-free survival (DFS) decreased from 96.8 to 80.1% in the presence of LVSI (p < 0.001). This association could not be shown in patients who had had lymphadenectomy (p = 0.136). Extra-pelvic recurrence occurred in 6.7% and 1% of the patients with and without LVSI, respectively, (p = 0.001). Any independent prognostic factor could not be detected in the multivariate analysis. CONCLUSIONS: Only LVSI and tumor grade were associated with DFS and disease-specific survival (DSS), respectively, in the 686 patients with stage IA endometrial cancer in the univariate analysis, since these associations could not be shown in multivariate analysis.

Reproducibility of lymphovascular space invasion (LVSI) assessment in endometrial cancer.

AIMS: Lymphovascular space invasion (LVSI) in endometrial cancer (EC) is an important prognostic variable impacting on a patient's individual recurrence risk and adjuvant treatment recommendations. Recent work has shown that grading the extent of LVSI further improves its prognostic strength in patients with stage I endometrioid EC. Despite this, there is little information on the reproducibility of LVSI assessment in EC. Therefore, we designed a study to evaluate interobserver agreement in discriminating true LVSI from LVSI mimics (Phase I) and reproducibility of grading extent of LVSI (Phase II). METHODS AND RESULTS: Scanned haematoxylin and eosin (H&E) slides of endometrioid EC (EEC) with a predefined possible LVSI focus were hosted on a website and assessed by a panel of six European gynaecological pathologists. In Phase I, 48 H&E slides were included for LVSI assessment and in Phase II, 42 H&E slides for LVSI grading. Each observer was instructed to apply the criteria for LVSI used in daily practice. The degree of agreement was measured using the two-way absolute agreement average-measures intraclass correlation coefficient (ICC). Reproducibility of LVSI assessment (ICC = 0.64, P < 0.001) and LVSI grading (ICC = 0.62, P < 0.001) in EEC was substantial among the observers. CONCLUSIONS: Given the good reproducibility of LVSI, this study further supports the important role of LVSI in decision algorithms for adjuvant treatment.

Prognostic factors for and pattern of lymph-node involvement in patients with operable cervical cancer.

PURPOSE: Lymph node metastases significantly worsen the prognosis in cervical carcinoma. Risk factors-pathological and patient related-could select patients at high risk for lymph node involvement. METHODS: This retrospective analysis was performed by analyzing data from patients with cervical carcinoma treated between 2000 and 2017 at the Department of Obstetrics and Gynecology of the University Hospital Ulm. RESULTS: In total, 261 patients with cervical carcinoma (International Federation of Gynecology and Obstetrics (FIGO) stage IA-IIB) and lymphadenectomy with at least 10 removed lymph nodes were available for analysis. Overall, 86 (33.0%) patients had lymph node metastases; 73 patients had pelvic lymph node metastases only and 13 patients had both pelvic and paraaortic lymph node metastases. Lymph node metastases were found most often in the region of the external iliac artery and obturator fossa, with 57.0% and 54.7% of all 86 node-positive patients, respectively. Univariable analyses showed that presence of lymph node metastases was significantly associated with both preoperative FIGO stage (p = 0.001) and final pathological tumor stage (p < 0.001), status of resection margin (p = 0.002), lymphovascular space invasion (LVSI), (p < 0.001) and vascular space invasion, (p < 0.001). In a multivariable logistic regression model with presence of lymph node metastases (yes/no) as binary response variable, only LVSI (p < 0.001) and body mass index (BMI), (p = 0.035) remained as significant independent predictors of lymph node involvement. Subgroup analyses showed that LVSI was a significant predictive factor for lymph node involvement in patients with a preoperatively assessed FIGO stage < IIB (p < 0.001), but not for patients with a preoperatively assessed FIGO stage ≥ IIB (p = 0.122). CONCLUSIONS: The risk factor LVSI should play an important role in deciding whether an individualized therapy concept is based on escalating or deescalating treatment. In future, the sentinel concept could reduce morbidity and at the same time provide an important prognostic assessment for a subset of cervical cancer patients.

Third Nerve Palsy as the Presenting Sign of Metastatic Endometrial Carcinoma with Lymphovascular Space Invasion.

We present a case of endometrial carcinoma (EC) presenting with a third cranial nerve palsy due to metastasis to the cavernous sinus. Although the tumour was only stage 1B, histopathologic features including higher grade and lymphovascular space invasion (LVSI) increase the risk of recurrent and metastatic disease. To our knowledge, this is the first case of EC presenting as a third cranial nerve palsy in the English-language ophthalmic literature. Clinicians should be aware that the risk of metastatic EC including neuro-ophthalmic presentations depends upon not only stage and grade but also the presence of unique histopathological findings such as LVSI.

Magnitude of risk for nodal metastasis associated with lymphvascular space invasion for endometrial cancer.

OBJECTIVES: While lymphvascular space invasion (LVSI) is a risk factor for nodal metastasis in endometrial cancer, the magnitude of risk is poorly described. We examined the risk of nodal metastasis associated with LVSI for various combinations of tumor grade and depth of invasion and examined the effect of LVSI on survival. METHODS: We identified patients with T1A (<50% myoinvasion) and T1B (>50% myoinvasion) endometrioid adenocarcinomas of the endometrium diagnosed between 2010 and 2012 and recorded in the National Cancer Database. The risk of nodal metastasis associated with LVSI stratified by grade and stage is reported. The association of LVSI and survival was examined using Kaplan-Meier analyses and Cox proportional hazards models. RESULTS: We identified 25,907 patients, including 3928 (15.2%) with LVSI. Among patients with LVSI, 21.0% had positive lymph nodes, compared to 2.1% in patients without LVSI (P<0.0001). In analyses stratified by stage and grade, LVSI was associated with increased risks of LN metastasis by a magnitude of 3 to over 10-fold. In a multivariable model controlling for clinical and demographic characteristics, the risk ratio of nodal disease with LVSI was 9.29 (95% CI, 7.29-11.84) for T1A tumors and 4.64 (95% CI 3.99-5.39) for T1B tumors. LVSI was associated with decreased survival even after adjustment for the presence of lymph node metastases (HR=1.92, 95% CI 1.56-2.36). CONCLUSIONS: LVSI is independently associated with lymph node metastases in women with apparent early-stage endometrial cancer and an independent predictor of survival even after adjustment for the presence of lymph node metastases.

Lymphovascular Space Invasion as a Risk Factor in Early Endometrial Cancer.

Management of early endometrial cancer is contentious these days with little agreement between oncologists as well as across MDTs or tumour boards and indeed across countries. This is because of the state of knowledge with regards to risk factors in early endometrial cancer; although we recognise risk factors affect outcome, we haven't yet been able to demonstrate that our treatments make a significant difference. We have reviewed available literature on LVSI and are able to demonstrate that it is an independent risk factor for nodal metastasis as well as distant recurrence. We need a randomised trial integrating grade and LVSI and testing therapeutic options of radiotherapy and chemotherapy. However, it is unlikely to see the light of day. Therefore, we are left with this knowledge of prognostic factors and it is our duty to integrate this into our decision-making during our multidisciplinary team meetings and make decisions tailored to individual patient circumstances.

Satellite lymphovascular space invasion: An independent risk factor in early stage cervical cancer.

OBJECTIVE: This study was performed to determine whether satellite LVSI in women with early stage cervical carcinoma is an independent prognostic factor for recurrence and survival. METHODS: A total of 210 eligible patients with FIGO stages IA2 and IB1 cervical carcinoma, who underwent radical hysterectomy or radical trachelectomy with pelvic lymphadenectomy between January 2000 and December 2012, were included. Variables studied included age, histology type, differentiation grade, tumor size (TS), depth of invasion (DI), lymph node metastasis (LNM), conjoined lymphovascular space invasion (LVSI) and satellite LVSI. Univariate and multivariate analyses were performed to define variables that best predict recurrence and survival. RESULTS: Univariate analysis showed that differentiation grade, depth of invasion, tumor size, lymph node metastasis, and both conjoined LVSI and satellite LVSI were significantly associated with recurrence and survival. Using multivariate analysis, differentiation grade (HR 3.63, 95%-CI 1.51-8.72), conjoined LVSI (HR 5.95, 95%-CI 1.57-22.53) and satellite LVSI (HR 7.45, 95%-CI 3.03-18.27) were independent prognostic factors for recurrence; LNM (HR 5.55, 95%-CI 1.52-20.26) and satellite LVSI (HR 8.94, 95%-CI 2.43-32.95) were prognostic factors for overall survival. For patients with low-risk cervical cancer without LNM only satellite LVSI correlated significantly with disease-free and overall survival. CONCLUSION: Differentiation grade, DI, TS, LNM, and conjoined LVSI as well as satellite LVSI were prognostic factors for DFS and OS. Satellite LVSI is the most important factor predicting DFS and OS in early stage cervical cancer, especially when lymph nodes are negative.

Quantitative assessment of lymph vascular space invasion (LVSI) provides important prognostic information in node-negative breast cancer.

BACKGROUND: Some studies investigating the prognostic value of lymph vascular space invasion (LVSI) have shown an association between LVSI and disease-free survival. Definitive criteria and optimal determination of this parameter remain unclear, however, especially regarding the clinical relevance of LVSI quantification. PATIENTS AND METHODS: A subset of node-negative breast carcinomas from premenopausal patients from the European Organization for the Research and Treatment of Cancer trial 10854 (assessing efficacy of perioperative chemotherapy patients with T1-T3, N0-2, and M0 breast cancer (BC) was selected and scored for LVSI. In 358 evaluable breast carcinomas, the number of LVSI foci and tumor cells was determined in the largest tumor embolus within the lymph vessels. These two parameters were multiplied to calculate the LVSI tumor burden (LVSI TB). The optimal cutoff for this parameter was calculated in a test set (N = 120), tested in a validation set (N = 238), and compared with simple quantitation of the number of LVSI foci. RESULTS: Tumors with a single LVSI focus are not associated with increased risk for relapse [hazard ratio (HR) 1.423, 95% confidence interval (CI) 0.762-2.656]. The LVSI TB had higher sensitivity and specificity compared with simple determination of the number of LVSI foci. LVSI TB was independently associated with disease-free survival in the validation set (HR 2.366, 95% CI 1.369-4.090, P = 0.002) in multivariate analysis and provided prognostic information in both the low- and high-risk node-negative BC groups (P < 0.001 and P = 0.007, respectively). CONCLUSION: The determination of the number of LVSI foci multiplied by the number of tumor cells gives the most reliable quantitative assessment of this parameter, which can provide prognostic information in node-negative BC.

Habitat-based radiomics enhances the ability to predict lymphovascular space invasion in cervical cancer: a multi-center study.

Introduction: Lymphovascular space invasion (LVSI) is associated with lymph node metastasis and poor prognosis in cervical cancer. In this study, we investigated the potential of radiomics, derived from magnetic resonance (MR) images using habitat analysis, as a non-invasive surrogate biomarker for predicting LVSI in cervical cancer. Methods: This retrospective study included 300 patients with cervical cancer who underwent surgical treatment at two centres (centre 1 = 198 and centre 2 = 102). Using the k-means clustering method, contrast-enhanced T1-weighted imaging (CE-T1WI) images were segmented based on voxel and entropy values, creating sub-regions within the volume ofinterest. Radiomics features were extracted from these sub-regions. Pearson correlation coefficient and least absolute shrinkage and selection operator LASSO) regression methods were used to select features associated with LVSI in cervical cancer. Support vector machine (SVM) model was developed based on the radiomics features extracted from each sub-region in the training cohort. Results: The voxels and entropy values of the CE-T1WI images were clustered into three sub-regions. In the training cohort, the AUCs of the SVM models based on radiomics features derived from the whole tumour, habitat 1, habitat 2, and habitat 3 models were 0.805 (95% confidence interval [CI]: 0.745-0.864), 0.873(95% CI: 0.824-0.922), 0.869 (95% CI: 0.821-0.917), and 0.870 (95% CI: 0.821-0.920), respectively. Compared with whole tumour model, the predictive performances of habitat 3 model was the highest in the external test cohort (0.780 [95% CI: 0.692-0.869]). Conclusions: The radiomics model based on the tumour sub-regional habitat demonstrated superior predictive performance for an LVSI in cervical cancer than that of radiomics model derived from the whole tumour.