Prognostic value of three-tiered scoring system for lymph-vascular space invasion in endometrial cancer: A systematic review and meta-analysis.

OBJECTIVE: To investigate the impact of lymph-vascular space invasion (LVSI) status on the prognosis of endometrial cancer (EC) according to a three-tiered scoring system for LVSI. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), and Clinical Trials.gov were searched from inception to September 1st, 2023. The analysis was conducted using STATA 16.0. RESULTS: A total of 9 studies with 4456 EC patients were included in the analysis. No LVSI was found in 72% of EC patients (95% CI 0.65-0.79), while focal and substantial LVSI were present in 16% (95% CI 0.11-0.21) and 13% (95% CI 0.08-018) of patients, respectively. Compared to the no LVSI group, the focal and substantial LVSI groups had poorer overall survival (for focal LVSI: HR 1.33, 95% CI 1.02-1.74; for substantial LVSI: HR 2.51, 95% CI 1.61-3.90), poorer disease-free survival (for substantial LVSI: HR 2.86, 95% CI 1.21-6.77), and an increased risk of recurrence, including pelvic recurrence (for focal LVSI: HR 2.05, 95% CI 1.03-4.07; for substantial LVSI: HR 6.06, 95% CI 3.31-11.08), distant recurrence (for focal LVSI: HR 2.04, 95% CI 1.42-2.92; for substantial LVSI: HR 3.36, 95% CI 2.35-4.793), and lymph node involvement (for focal LVSI: OR 3.52, 95% CI 1.339.34; for substantial LVSI: OR 5.42, 95% CI 2.78-10.58). Substantial LVSI was more prone to pelvic recurrence (HR 1.82, 95% CI 1.05-3.15) and distant recurrence (HR 2.21, 95% CI 1.48-3.28) than focal LVSI. CONCLUSIONS: EC patients with focal and substantial LVSI had poorer survival, recurrence, and a higher incidence of lymph node metastasis than patients without LVSI. The substantial LVSI group was associated with even worse prognosis than the focal LVSI group. The three-tiered LVSI scoring system might effectively predict the prognosis of EC and guide clinical decision-making. PROTOCOL REGISTRATION: CRD 42023451793.

Multiparametric mri-based radiomics nomogram for predicting lymph-vascular space invasion in cervical cancer.

PURPOSE: To develop and validate a multiparametric magnetic resonance imaging (mpMRI)-based radiomics model for predicting lymph-vascular space invasion (LVSI) of cervical cancer (CC). METHODS: The data of 177 CC patients were retrospectively collected and randomly divided into the training cohort (n=123) and testing cohort (n = 54). All patients received preoperative MRI. Feature selection and radiomics model construction were performed using max-relevance and min-redundancy (mRMR) and the least absolute shrinkage and selection operator (LASSO) on the training cohort. The models were established based on the extracted features. The optimal model was selected and combined with clinical independent risk factors to establish the radiomics fusion model and the nomogram. The diagnostic performance of the model was assessed by the area under the curve. RESULTS: Feature selection extracted the thirteen most important features for model construction. These radiomics features and one clinical characteristic were selected showed favorable discrimination between LVSI and non-LVSI groups. The AUCs of the radiomics nomogram and the mpMRI radiomics model were 0.838 and 0.835 in the training cohort, and 0.837 and 0.817 in the testing cohort. CONCLUSION: The nomogram model based on mpMRI radiomics has high diagnostic performance for preoperative prediction of LVSI in patients with CC.

A nomogram of preoperative indicators predicting lymph vascular space invasion in cervical cancer.

PURPOSE: To develop predictive nomograms of lymph vascular space invasion (LVSI) in patients with early-stage cervical cancer. METHODS: We identified 403 patients with cervical cancer from the Affiliated Hospital of Jiangnan University from January 2015 to December 2019. Patients were divided into the training set (n = 242) and the validation set (n = 161), with patients in the training set subdivided into LVSI (+) and LVSI (-) groups according to postoperative pathology. Preoperative hematologic indexes were compared between the two subgroups. Univariate and multivariate logistic regression analyses were used to analyze the independent risk factors for LVSI, from which a nomogram was constructed using the R package. RESULTS: LVSI (+) was present in 94 out of 242 patients in the training set, accompanied by a significant increase in the preoperative squamous cell carcinoma antigen (SCC), white blood cells (WBC), neutrophil (NE), platelet (PLT), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), and tumor size (P < 0.05). Univariate analysis showed that SCC, WBC, NE, NLR, PLR, SII, and tumor size were correlated with LVSI (P < 0.05), and multivariate analysis showed that tumor size, SCC, WBC, and NLR were independent risk factors for LVSI (P < 0.05). A nomogram was correspondingly established with good performance in predicting LVSI [training: ROC-AUC = 0.845 (95% CI: 0.731-0.843) and external validation: ROC-AUC = 0.704 (95% CI: 0.683-0.835)] and high accuracy (training: C-index = 0.787; external validation: C-index = 0.759). CONCLUSION: The nomogram based on preoperative tumor size, SCC, WBC, and NLR had excellent accuracy and discriminative capability to assess the risk of LVSI in early-stage cervical cancer patients.

Does lymph node assessment change the prognostic significance of substantial LVSI and p53 status in endometrial endometrioid carcinoma?

OBJECTIVE: The PORTEC-2 update suggested that substantial lymphovascular space invasion (LVSI) and abnormal p53 expression (p53abnl) predict for poorer outcomes and that these patients should be treated with external beam radiation therapy (EBRT). We aim to determine if patients with these risk factors who undergo a lymph node (LN) assessment show similar outcomes. METHODS: We retrospectively reviewed 126 patients with FIGO 2009 stage IA grade 3, stage IB grade 1-2, and stage IIIC (positive LN but no other stage II/III risk factors) endometrioid endometrial cancer who underwent LN assessment. Local (LR), regional recurrences (RR), and distant metastases were analyzed using competing risk methods, and overall survival (OS) was analyzed using Kaplan-Meier. RESULTS: Median follow-up time was 37.2 months. OS was significantly different between patients with and without p53abnl expression (16.7% versus 3.1% deceased), and between patients with and without LVSI (11.1% versus 1.5% deceased; p < 0.01 for both). The 2-year cumulative incidence of LR for patients with p53abnl versus wild type p53 and LVSI versus no LVSI was 11.1% (95% CI 0-25.6) versus 2.2% (95% CI 0-5.25; p = 0.04), and 11.4% (95% CI 2.0-20.9) versus 0%, respectively (p < 0.01). The 2-year cumulative RR in patients with LVSI versus no LVSI was 6.9% (95% CI 0-14.4) versus 0% (p = 0.05). No patients who completed pelvic RT experienced an in-field recurrence. CONCLUSIONS: Despite LN assessment, patients with high-intermediate risk early-stage or stage IIIC (with positive lymph nodes only but no other stage II or III risk factors) endometrial cancer with p53abnl expression and/or LVSI have worse outcomes. These patients may derive benefit from intensification with EBRT to improve local and pelvic control.

MR-Based Radiomics Nomogram of Cervical Cancer in Prediction of the Lymph-Vascular Space Invasion preoperatively.

BACKGROUND: Lymph-vascular space invasion (LVSI) is an unfavorable prognostic factor in cervical cancer. Unfortunately, there are no current clinical tools for the preoperative prediction of LVSI. PURPOSE: To develop and validate an axial T1 contrast-enhanced (CE) MR-based radiomics nomogram that incorporated a radiomics signature and some clinical parameters for predicting LVSI of cervical cancer preoperatively. STUDY TYPE: Retrospective. POPULATION: In all, 105 patients were randomly divided into two cohorts at a 2:1 ratio. FIELD STRENGTH/SEQUENCE: T1 CE MRI sequences at 1.5T. ASSESSMENT: Univariate analysis was performed on the radiomics features and clinical parameters. Multivariate analysis was performed to determine the optimal feature subset. The receiver operating characteristic (ROC) analysis was performed to evaluate the performance of prediction model and radiomics nomogram. STATISTICAL TESTS: The Mann-Whitney U-test and the chi-square test were used to evaluate the performance of clinical characteristics and LVSI status by pathology. The minimum-redundancy/maximum-relevance and recursive feature elimination methods were applied to select the features. The radiomics model was constructed using logistic regression. RESULTS: Three radiomics features and one clinical characteristic were selected. The radiomics nomogram showed favorable discrimination between LVSI and non-LVSI groups. The AUC was 0.754 (95% confidence interval [CI], 0.6326-0.8745) in the training cohort and 0.727 (95% CI, 0.5449-0.9097) in the validation cohort. The specificity and sensitivity were 0.756 and 0.828 in the training cohort and 0.773 and 0.692 in the validation cohort. DATA CONCLUSION: T1 CE MR-based radiomics nomogram serves as a noninvasive biomarker in the prediction of LVSI in patients with cervical cancer preoperatively. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1420-1426.

Risk of parametrial invasion in women with early stage cervical cancer: a meta-analysis.

PURPOSE: To first evaluate the predictive value of lymph-vascular space invasion (LVSI) and pelvic lymph node metastases (LNM) to parametrial invasion (PI) in patients with early stage cervical cancer. METHODS: A systematic search of electronic databases was conducted to identify publications exploring the association between LVSI, LNM, and PI. The following databases were searched: PubMed/Medline and Web of Science. Twenty relevant studies were included. Pooling of results was done based on these studies and a diagnostic meta-analysis was performed. RESULTS: 20 articles and a total of 7373 cases were included in the meta-analysis. 17 studies analyzed the correlation between LVSI and PI and 18 studies evaluated the correlation between LNM and PI. The existence of LVSI accelerated PI with OR being 7.37 (95% CI 5.70-9.54) in fixed-effect model and 7.32 (95% CI 4.65-10.39) in random effects model. LVSI shows high sensitivity of 0.80 and the AUC was 0.82. The existence of LNM accelerated PI. LNM shows the highest specificity of 0.90 and the AUC was 0.77. CONCLUSIONS: Both LVSI and LNM are associated with PI. Conization and lymphadenectomy might be helpful to predict the parametrial status of patients with early stage cervical cancer. In addition, the results of this meta-analysis are helpful for designing further prospective clinical trials.

Relationship between minimally invasive hysterectomy, pelvic cytology, and lymph vascular space invasion: a single institution study of 458 patients.

OBJECTIVE: The aim of this study is to determine whether a minimally invasive approach to hysterectomy is associated with an increased rate of lymph vascular space invasion (LVSI) and/or malignant pelvic peritoneal cytology in endometrial cancer. METHODS: We performed a single institution analysis of 458 women with endometrial cancer who underwent either total abdominal hysterectomy (TAH) or minimally invasive hysterectomy (MIH) with use of a disposable uterine manipulator. All patients had endometrial cancer diagnosed by endometrial biopsy at a single academic institution between 2002 and 2012. Exclusion criteria were pre-operative D&C and/or hysteroscopy, uterine perforation or morcellation, and conversion to laparotomy. Multivariate logistic regression models to determine if type of hysterectomy predicts either LVSI or presence of abnormal cytology were controlled for grade, stage, depth of invasion, tumor size, cervical and adnexal involvement. RESULTS: LVSI was identified in 39/214 (18%) MIH and 44/242 (18%) TAH (p=0.99). Pelvic washings were malignant in 14/203 (7%) MIH and 16/241 (7%) TAH (p=1.0). Washings were atypical or inconclusive in 16/203 (8%) MIH and 6/241 (2.5%) TAH (p=0.014). In multivariate analyses, type of hysterectomy was not a significant predictor of either LVSI (p=0.29) or presence of malignant washings (p=0.66), but was a predictor of atypical or inconclusive washings (p=0.03). CONCLUSION: Minimally invasive hysterectomy with use of a uterine manipulator for endometrial cancer is not associated with LVSI or malignant cytology. Algorithms that better determine the etiology and implications of inconclusive or atypical pelvic cytology are needed to inform the possible additional risk associated with a minimally invasive approach to endometrial cancer.

The impact of lymph vascular space invasion on recurrence and survival in patients with early stage endometrial cancer.

The aim of this study was to determine impact of lymph vascular space involvement (LVSI) on recurrence and survival in early stage of endometrial cancer. From 1991 through 2010, all endometrial cancer patients at University Hospital of Bari, Italy were identified. The Log-rank test and Kaplan-Meyer methods were used for time-to-event analysis to evaluate the effects of on lymph vascular space involvement recurrence rate and survival time. Of the 560 endometrial cancer patients, 525 underwent primary surgery. Of those, 399 had early stage disease. Three hundred and forty women were not found to have LVSI, whereas 59 were found to have lymph vascular space involvement. Forty-nine (12%) patients developed a recurrence and 20 of them showed lymph vascular space involvement. The statistical analysis demonstrated that LVSI was strongly associated with a poor survival (P < 0.0001). Lymph vascular space involvement is associated with a high risk of recurrence and poor overall survival in early stage of endometrial cancer; therefore, the clinical decision to decide whether or not a patient with early stage endometrial cancer should receive adjuvant therapy should be included the evaluation of lymph vascular space involvement.

Prognostic evaluation of lymph-vascular space invasion in patients with endometrioid and non-endometrioid endometrial cancer: A multicenter study.

INTRODUCTION: The prognostic value of lymph-vascular space invasion (LVSI) on endometrial cancer (EC) remains controversial. This study aimed to explore the impact of LVSI on patients with endometrioid and non-endometrioid EC in China. MATERIALS AND METHODS: We analyzed EC patients who underwent surgery from 2010 to 2019 in seven Chinese hospitals retrospectively and stratified patients based on histopathologic types and LVSI status. Endpoints were disease-free survival (DFS) and overall survival (OS). Propensity score matching (PSM) algorithm was used to balance the confounding factors. The survival was examined using Kaplan-Meier analysis. Cox proportional hazards regression analyses were used to find prognostic independent risk factors. RESULTS: Among 3715 EC patients, LVSI positive rate was 9.31% (346/3715). After matching, LVSI present group had shorter DFS (P = 0.005), and similar OS (P = 0.656) than LVSI absent group for endometrioid EC patients. For non-endometrioid EC patients, there was no statistical difference in either DFS (P = 0.536) or OS (P = 0.512) after matching. The multivariate Cox analysis showed that LVSI was an independent risk factor of DFS [hazard ratio (HR) 2.62, 95% confidence intervals (CI) 1.35-5.10, P = 0.005] and not OS (HR 1.24, 95%CI 0.49-3.13, P = 0.656) for endometrioid EC patients. It was not a prognostic factor of either DFS (HR 1.28, 95%CI 0.58-2.81, P = 0.539) or OS (HR 1.33, 95%CI 0.55-3.13, P = 0.515) for non-endometrioid EC patients. CONCLUSION: LVSI is an adverse prognostic factor for endometrioid EC patients and has no impact on non-endometrioid EC patients. Necessity of postoperative adjuvant therapy based on LVSI needs to be carefully considered for non-endometrioid EC patients.

Lymph Node Involvement in Early-Stage Cervical Cancer: Is Lymphangiogenesis a Risk Factor? Results from the MICROCOL Study.

Background: In patients with cervical cancer, the presence of tumoral lymph-vascular space invasion (LVSI) is the main risk factor for pelvic lymph node metastasis (PLNM). The objective of this study was to evaluate the presence of several markers of lymphangiogenesis in early-stage cervical cancer and their correlation with PLNM and tumoral recurrence. Materials and Methods: Seventy-five patients with early-stage cervical carcinoma underwent sentinel lymph node (SLN) sampling in association with complete pelvic lymph node dissection. Primary tumors were stained with the following markers: Ki67, D2-40, CD31 and VEGF-C. A 3-year follow-up was performed to evaluate the disease-free survival. Results: Overall, 14 patients (18.6%) had PLNM. Positive LVSI was seen in 29 patients (38.6%). There was a significant correlation between LVSI evidenced by H/E staining and PLNM (p < 0.001). There was no correlation between high Ki67, CD31, D2-40, and VEGF-C staining with PLNM or tumor recurrence. Conclusions: Our data support that lymphatic spread does not require the proliferation of new lymphatic endothelial cells in early-stage cervical cancer. These results emphasize the importance of pre-existing peritumoral lymphatic vessels in the metastatic process in early cervical cancer. None of the markers of lymphangiogenesis and proliferation assessed in this study were predictive of PLNM or recurrence.

Prediction of Postoperative Pathologic Risk Factors in Cervical Cancer Patients Treated with Radical Hysterectomy by Machine Learning.

Pretherapeutic serological parameters play a predictive role in pathologic risk factors (PRF), which correlate with treatment and prognosis in cervical cancer (CC). However, the method of pre-operative prediction to PRF is limited and the clinical availability of machine learning methods remains unknown in CC. Overall, 1260 early-stage CC patients treated with radical hysterectomy (RH) were randomly split into training and test cohorts. Six machine learning classifiers, including Gradient Boosting Machine, Support Vector Machine with Gaussian kernel, Random Forest, Conditional Random Forest, Naive Bayes, and Elastic Net, were used to derive diagnostic information from nine clinical factors and 75 parameters readily available from pretreatment peripheral blood tests. The best results were obtained by RF in deep stromal infiltration prediction with an accuracy of 70.8% and AUC of 0.767. The highest accuracy and AUC for predicting lymphatic metastasis with Cforest were 64.3% and 0.620, respectively. The highest accuracy of prediction for lymphavascular space invasion with EN was 59.7% and the AUC was 0.628. Blood markers, including D-dimer and uric acid, were associated with PRF. Machine learning methods can provide critical diagnostic prediction on PRF in CC before surgical intervention. The use of predictive algorithms may facilitate individualized treatment options through diagnostic stratification.

MRI- and Histologic-Molecular-Based Radio-Genomics Nomogram for Preoperative Assessment of Risk Classes in Endometrial Cancer.

High- and low-risk endometrial carcinoma (EC) differ in whether or not a lymphadenectomy is performed. We aimed to develop MRI-based radio-genomic models able to preoperatively assess lymph-vascular space invasion (LVSI) and discriminate between low- and high-risk EC according to the ESMO-ESGO-ESTRO 2020 guidelines, which include molecular risk classification proposed by "ProMisE". This is a retrospective, multicentric study that included 64 women with EC who underwent 3T-MRI before a hysterectomy. Radiomics features were extracted from T2WI images and apparent diffusion coefficient maps (ADC) after manual segmentation of the gross tumor volume. We constructed a multiple logistic regression approach from the most relevant radiomic features to distinguish between low- and high-risk classes under the ESMO-ESGO-ESTRO 2020 guidelines. A similar approach was taken to assess LVSI. Model diagnostic performance was assessed via ROC curves, accuracy, sensitivity and specificity on training and test sets. The LVSI predictive model used a single feature from ADC as a predictor; the risk class model used two features as predictors from both ADC and T2WI. The low-risk predictive model showed an AUC of 0.74 with an accuracy, sensitivity, and specificity of 0.74, 0.76, 0.94; the LVSI model showed an AUC of 0.59 with an accuracy, sensitivity, and specificity of 0.60, 0.50, 0.61. MRI-based radio-genomic models are useful for preoperative EC risk stratification and may facilitate therapeutic management.

Semiquantitative evaluation of lymph-vascular space invasion in patients affected by endometrial cancer: Prognostic and clinical implications.

OBJECTIVES: The interpretation of lymph-vascular space invasion (LVSI) is usually qualitative, as presence or absence. The aim of this study is to investigate the prognostic role of LVSI in patients affected by endometrial cancer, when evaluated with a semiquantitative analysis. METHODS: This retrospective multicentre study enrolled patients who received a histologically confirmed diagnosis of endometrial cancer. The assessment of LVSI was semiquantitative in accordance with the three-tiered scoring system (absent, focal and diffuse). RESULTS: Among 1258 patients with surgical-stage endometrial cancer, LVSI has been found in 32.8% of cases (n = 412), whose 12.7% (n = 160) were focal, and 20% (n = 252) diffuse. The rate of lymph node metastasis increased from the 5% in patients with no LVSI to 15% in patients with focal LVSI and 33% in those with diffuse LVSI (p < 0.001). Distant recurrences were more frequent in patients with diffuse LVSI than in focal or no LVSI (24.9% versus 14.7% and 6.6%, respectively, p < 0.001). Diffuse LVSI was found to significantly increase the risk of distant metastasis (adjusted odds ratio (A OR) 2.57, p < 0.001). Adjuvant radiation were associated with improved overall survival (OS) and disease-free survival (DFS) in patients with diffuse LVSI. CONCLUSION: The presence of diffuse LVSI is an independent risk factor for both lymph node metastasis and distant recurrence in endometrial cancer patients, and it is associated with a significantly decreased OS and DFS. Adjuvant radiation improved survival regardless of grading, histotype and lymph nodal metastasis in women with diffuse LVSI.

Lymph-Vascular Space Invasion in Patients with Stages IA2-IIA2 Cervical Cancer Treated with Laparoscopic versus Open Radical Hysterectomy.

OBJECTIVE: To explore the relationship between laparoscopic radical hysterectomy (LRH) and cervical cancer lymph-vascular space invasion (LVSI) by comparing the prevalence of LVSI in cervical cancer patients who underwent LRH versus open radical hysterectomy (ORH). METHODS: The study participants were 1087 cervical cancer patients (FIGO 2009 stages IA2-IIA2) with pathologically confirmed with or without LVSI who underwent radical hysterectomy at Shengjing Hospital of China Medical University from 2013 through 2018. The patients were divided according to the type of surgical procedure into an LRH group (n=148) and an ORH group (n=939). RESULTS: In the LRH group, 31.76% of patients (47/148) had LVSI-positive tumors compared to 33.23% of patients (312/939) in the ORH group; the difference was not significant (p=0.724). No between-group differences in LVSI prevalence according to lymph node metastasis, interstitial infiltration depth, differentiation degree, and parametrial infiltration were found. However, the number of LVSI-positive patients whose cervical cancer lesions >4 cm (stage I B2 and II A2) was significantly higher in the LRH group than in the ORH group (Odds Ratio [OR] 0.333, 95% confidence interval [CI] 0.157-0.706, p=0.005). The 3-Year disease-free survival (DFS) in the LRH group is lower than that in the ORH group (94.75% vs 97.27%), but there was no significance (P=0.187). Furthermore, the percentage of LVSI-positive tumors in patients with lymph node metastases was significantly higher than those without lymph node metastases (OR 2.897, 95% CI 2.129-3.942, p=0.000). The 3-Year DFS were 98.22% in the LVSI negative patients and 93.78% in the LVSI positive patients, the difference was significant (P=0.002). CONCLUSION: A higher risk of lymph node metastasis and a lower 3-Year DFS was found in the LVSI-positive patients. In case of LVSI, it would be dangerous to treat patient in laparoscopy, especially in case of cervical cancer lesions >4cm.

Lymph-vascular space invasion (LVSI) as a strong and independent predictor for non-locoregional recurrences in endometrial cancer: a Danish Gynecological Cancer Group Study.

OBJECTIVE: To evaluate the effect of lymph-vascular space invasion (LVSI) on location of recurrences in Danish patients with endometrial cancer. METHODS: This national cohort study (2005-2012) included 4,380 radically operated patients (no visual tumor, all distant metastasis removed). LVSI status was recorded in 3,377 (77.1%). In stage I patients, 2.6% received adjuvant radiotherapy and 1.4% adjuvant chemotherapy. Adjusted Cox regression was used to compare actuarial recurrence rates. RESULTS: LVSI was present in 18.7% of 3,377 patients with known LVSI status. Of these, 7.6% stage I patients with LVSI experienced an isolated locoregional and 19.4% a non-locoregional recurrence. Compared to no LVSI, 5-year recurrence rate was higher (25.5% vs. 8.5%) in patients with LVSI and the frequency of distant recurrences was strikingly higher (stage I: 15.2% vs. 2.7%), the effect being similar across International Federation of Gynecology and Obstetrics stages and histological types. In intermediate-risk stage I patients with LVSI, 8.0% experienced an isolated locoregional recurrence compared to 20.1% with non-locoregional recurrence, giving these patients a seriously adverse risk of survival. A separate analysis in patients with recurrences demonstrated that those with LVSI had significantly more distant recurrences (55.4% vs. 29.9%) and fewer isolated vaginal recurrences (24.3% vs. 42.8%) than patients with no LVSI. CONCLUSION: LVSI is a strong independent risk factor for the development of non-locoregional recurrences even in intermediate-risk stage I endometrial cancer. The non-locoregional recurrence pattern suggests a future focus for optimization of postoperative treatment in these patients.

Substantial lymph-vascular space invasion (LVSI) is a significant risk factor for recurrence in endometrial cancer--A pooled analysis of PORTEC 1 and 2 trials.

BACKGROUND: Lymph-vascular space invasion (LVSI) is an important adverse prognostic factor in endometrial cancer (EC). However, its role in relation to type of recurrence and adjuvant treatment is not well defined, and there is significant interobserver variation. This study aimed to quantify LVSI and correlate this to risk and type of recurrence. METHODS: In the post operative radiation therapy in endometrial carcinoma (PORTEC)-trials stage I EC patients were randomised to receive external beam radiotherapy (EBRT) versus no additional treatment after surgery (PORTEC-1, n=714), or to EBRT versus vaginal brachytherapy (PORTEC-2, n=427). In tumour samples of 926 (81.2%) patients with endometrioid tumours LVSI was quantified using 2-, 3- and 4-tiered scoring systems. Cox proportional hazard models were used for time-to-event analysis. RESULTS: Any degree of LVSI was identified in 129 cases (13.9%). Substantial LVSI (n=44, 4.8%) using the 3-tiered approach had the strongest impact on the risk of distant metastasis (hazard ratio (HR) 4.5 confidence interval (CI) 2.4-8.5). In multivariate analysis (including: age, depth of myometrial invasion, grade, treatment) substantial LVSI remained the strongest independent prognostic factor for pelvic regional recurrence (HR 6.2 CI 2.4-16), distant metastasis (HR 3.6 CI 1.9-6.8) and overall survival (HR 2.0 CI 1.3-3.1). Only EBRT (HR 0.3 CI 0.1-0.8) reduced the risk of pelvic regional recurrence. CONCLUSIONS: Substantial LVSI, in contrast to focal or no LVSI, was the strongest independent prognostic factor for pelvic regional recurrence, distant metastasis and overall survival. Therapeutic decisions should be based on the presence of substantial, not 'any' LVSI. Adjuvant EBRT and/or chemotherapy should be considered for stage I EC with substantial LVSI.

Surgical approach and long-term clinical outcome in women with microinvasive cervical cancer.

AIM: To assess the efficacy and safety of conservative surgical approach for microinvasive cervical cancer with regards to cone margins status and lymph vascular space invasion (LVSI). PATIENTS AND METHODS: This was a multicentre retrospective cohort study of 153 women diagnosed with microinvasive cervical cancer over a 10 years period (1993-2003). RESULTS: In conservatively-treated women (n=80), neither cancer mortality nor disease relapse after 184.5 ± 20.5 months of follow-up was detected. Residual disease in women who underwent secondary surgery was significantly related to positive margins on the primary cone excision (p=0.005) while no correlation with LVSI emerged. CONCLUSION: Conization can represent the definitive treatment for stage IA1, if surgical margins are cancer-free, independently of LVSI. A conservative surgical approach could also be considered in women with IA2 cervical cancer when preservation of fertility is strongly requested. A close long-term surveillance should be scheduled for conservatively-treated women.

Lymph-vascular space invasion (LVSI) as a strong and independent predictor for non-locoregional recurrences in endometrial cancer: a Danish Gynecological Cancer Group Study / 부인종양

OBJECTIVE: To evaluate the effect of lymph-vascular space invasion (LVSI) on location of recurrences in Danish patients with endometrial cancer. METHODS: This national cohort study (2005–2012) included 4,380 radically operated patients (no visual tumor, all distant metastasis removed). LVSI status was recorded in 3,377 (77.1%). In stage I patients, 2.6% received adjuvant radiotherapy and 1.4% adjuvant chemotherapy. Adjusted Cox regression was used to compare actuarial recurrence rates. RESULTS: LVSI was present in 18.7% of 3,377 patients with known LVSI status. Of these, 7.6% stage I patients with LVSI experienced an isolated locoregional and 19.4% a non-locoregional recurrence. Compared to no LVSI, 5-year recurrence rate was higher (25.5% vs. 8.5%) in patients with LVSI and the frequency of distant recurrences was strikingly higher (stage I: 15.2% vs. 2.7%), the effect being similar across International Federation of Gynecology and Obstetrics stages and histological types. In intermediate-risk stage I patients with LVSI, 8.0% experienced an isolated locoregional recurrence compared to 20.1% with non-locoregional recurrence, giving these patients a seriously adverse risk of survival. A separate analysis in patients with recurrences demonstrated that those with LVSI had significantly more distant recurrences (55.4% vs. 29.9%) and fewer isolated vaginal recurrences (24.3% vs. 42.8%) than patients with no LVSI. CONCLUSION: LVSI is a strong independent risk factor for the development of non-locoregional recurrences even in intermediate-risk stage I endometrial cancer. The non-locoregional recurrence pattern suggests a future focus for optimization of postoperative treatment in these patients.

Relationship among Lymph Vascular Space Invasion with Clinicopathological Factors and Prognosis in Early Cervical Cancer / 实用妇产科杂志

Objective:To investigate the relationship among lymph vascular space invasion (LVSI) with clinicopathological factors and prognosis in early cervical cancer(CC).Methods:Retrospective analysis was conducted on 280 cases of early CC that were surgically treated at Dalian Maternal and Child Health Care hospital between January 2009 and June 2012.Univariate analysis was performed to study the relationship between LVSI and clinicopathological factors,the clinicopathological factors statistically associated with LVSI in univariate analysis were studied by multivariate analysis to identify the independent risk factors of LVSI.Results:①Univariate analysis showed that histological type,histological differentiation,lymph node metastasis and cervical stromal invasion depth were significantly correlated with LVSI (P ＜ O.05).Multivariate analysis showed that LVSI was an independent risk factor for differentiation,lymph node metastasis,and the depth of invasion.②The 5-year disease free survival(DFS) of LVSI positive patients was 74％,and the overall survival(OS) was 80％.The 5-year DFS and OS of LVSI negative patients were 93％ (P ＜ 0.05).Conclusions:LVSI can reflect the potential risk of lymph node metastasis to some extent.LVSI is the independent risk factor of lymph node metastasis and can significantly reduce the DFS and OS.Patients with LVSI positive may have deeper infiltration and poorer differentiation,but more studies are needed to confirm it.

The effect of lymph-vascular space invasion on clinicopathologic features in patients with endometrial cance / 대한산부인과학회지

OBJECTIVE: The aim of this study was to evaluate the effect of lymph-vascular space invasion (LVSI) on clinicopathologic features and outcomes in patients with endometrial cancer. METHODS: All women who were surgically treated for endometrial cancer at the Cheil General Hospital & Women's Healthcare Center between January 2000 and December 2003 were eligible. One hundred-forty one patients underwent retrospective review of medical record. Pathologic findings of LVSI were reviewed and divided in LVSI-positive group and LVSI-negative. Statistical analysis was performed by dBSTAT-4. RESULTS: Fifty-five patients (39%) were LVSI-positive and eighty-six patients (61%) were LVSI-negative. LVSI-positive patients were statistically older than LVSI-negative. LVSI-positive patients had more abnormal cytology, poorer differentiation, larger tumor size (diameter>2 cm), more myometrial invasion. more pelvic nodal metastasis, more paraaortic nodal metastasis, and more advanced stage. There was no difference between the two groups in the percentage of patients with gravidity, parity, histologic types (endometrioid vs nonendometrioid). CONCLUSION: LVSI-positive patients with endometrial cancer are generally older, consistent with more abnormal cytology, poorer differentiation, larger tumor size, more myometrial invasion, more lymph-node metastasis, and more advanced-stage disease. So, LVSI should be a consideration in appropriate treatment in endometrial cancer.