Added value of shear-wave elastography in the prediction of extracapsular extension and seminal vesicle invasion before radical prostatectomy / 亚洲男科学杂志(英文版)

The purpose of this study was to analyze the value of transrectal shear-wave elastography (SWE) in combination with multivariable tools for predicting adverse pathological features before radical prostatectomy (RP). Preoperative clinicopathological variables, multiparametric magnetic resonance imaging (mp-MRI) manifestations, and the maximum elastic value of the prostate (Emax) on SWE were retrospectively collected. The accuracy of SWE for predicting adverse pathological features was evaluated based on postoperative pathology, and parameters with statistical significance were selected. The diagnostic performance of various models, including preoperative clinicopathological variables (model 1), preoperative clinicopathological variables + mp-MRI (model 2), and preoperative clinicopathological variables + mp-MRI + SWE (model 3), was evaluated with area under the receiver operator characteristic curve (AUC) analysis. Emax was significantly higher in prostate cancer with extracapsular extension (ECE) or seminal vesicle invasion (SVI) with both P < 0.001. The optimal cutoff Emax values for ECE and SVI were 60.45 kPa and 81.55 kPa, respectively. Inclusion of mp-MRI and SWE improved discrimination by clinical models for ECE (model 2 vs model 1, P = 0.031; model 3 vs model 1, P = 0.002; model 3 vs model 2, P = 0.018) and SVI (model 2 vs model 1, P = 0.147; model 3 vs model 1, P = 0.037; model 3 vs model 2, P = 0.134). SWE is valuable for identifying patients at high risk of adverse pathology.

Valor de la ruptura capsular y extensión extranodal en el ganglio centinela como predictores del estado axilar en pacientes con cáncer de mama T1-T2 / Significance of extracapsular extension in sentinel lymph nodes as a predictor of axillary lymph node status in T1-T2 breast cancer patients

Introducción: Identificar aquellas pacientes con cáncer de mama en estadíos iniciales que no se benefician de la linfadenectomía (LA), a pesar de contar con ganglios centinela positivos, constituye un desafío. El ensayo ACOSOG-Z0011 modificó el paradigma de la cirugía axilar, pero aún no está claro qué efecto tiene la ruptura capsular (RC) y su extensión (EEC) en el compromiso axilar. Material y método: Se incluyeron 214 pacientes intervenidas quirúrgicamente entre 2009-2019 en el Centro mamario del Instituto Alexander Fleming, con cáncer de mama en T1-2, en las que la biopsia de ganglio centinela (BGC) resultó positiva, y se realizó LA. Se realizaron comparaciones entre aquellas pacientes con y sin RC. Las pacientes con RC fueron divididas en dos grupos, según la EEC fuera mayor o igual a 2 mm, o menor a 2 mm. Para los distintos grupos de pacientes, se analizaron variables clínicas y anatomo-patológicas, incluyendo edad, estado menopáusico, subtipo biológico, grado nuclear, tamaño tumoral, invasión linfovascular (ILV) y multicentricidad. Resultados: La RC se asoció a una mayor probabilidad de presentar ganglios no centinela positivos, y en particular a la presencia de 4 o más ganglios positivos. Este grupo de pacientes presentó con más frecuencia ILV. En cuanto a la EEC, no hallamos diferencias significativas de acuerdo a la extensión de la ruptura (EEC<2 mm y EEC≥2 mm), aunque en el análisis uni y multivariado evidenció un mayor riesgo de presentar ≥4 ganglios positivos en el grupo de pacientes con EEC≥2 mm. Discusión: En línea con la bibliografía actual, encontramos que la RC es un hallazgo frecuente y que se asocia a una mayor probabilidad de presentar metástasis ganglionar, en especial 4 o más ganglios positivos. Al separar a las pacientes de acuerdo a la EEC, no hallamos diferencias en cuanto a la proporción de pacientes con ganglios positivos en la LA. Estos resultados difieren de los obtenidos por otros centros, en donde se ha demostrado una mayor probabilidad de contar con ganglios no centinela positivos en el grupo de pacientes con EEC>2mm. Conclusiones: En la bibliografía actual existe consenso en relación al rol de la RC como factor de riesgo, y nuestros resultados apoyan esta hipótesis. Sin embargo, resulta menos claro el papel que juega la magnitud de la EEC. Esto podría deberse, por un lado, a la falta que bibliografía disponible, y por otro, a la falta de consenso para determinar la medición de la EEC En línea con publicaciones recientes que no hallan diferencias significativas en la recurrencia de la enfermedad a largo plazo según la magnitud de la EEC, será fundamental continuar con un futuro análisis que contemple estos aspectos en nuestra población. Al día de hoy, no contamos con evidencia que nos permita afirmar que las pacientes con EEC<2 mm puedan beneficiarse de la omisión de LA

Introduction: The identification of those early breast cancer patients with no clear benefit from axillary lymph node dissection (ALND) in spite of the presence of positive sentinel lymph nodes (SLNs), remains controversial. Although the ACOSOG-Z001 trial has significantly altered management of the axilla, the role played by the extracapsular extension (ECE) is still a subject of debate. Materials and method: In the present study, we analysed 214 early breast cancer patients with positive SLN biopsy, who underwent ALND at Instituto Alexander Fleming between 2009 and 2019. Patients were divided into two categories based on the presence or absence of ECE; those patients with ECE were further divided based on the extent of ECE (ECE<2 mm and ECE≥2 mm). Analysis of clinical-pathological parameters was performed, including age, menopausal status, tumor subtype, nuclear grade, tumor size, lymphovascular invasion (LVI) and multicentricity. Results: ECE was associated with an increased probability of additional positive nodes in the ALND, and these patients were also more likely to have 24 positive nodes. LVI was increased in patients with ECE. Additionally, we found no significant differences regarding the number of positive nodes when comparing patients according to the extent of ECE (ECE<2 mm and ECE≥2 mm). Univariate and multivariate analyses of factors associated with involvement of ≥4 nodes at completion ALND resulted in an increased odds ratio for patients with ECE ≥2 mm. Discussion: In line with recent literature, we found ECE is frequently observed in breast cancer patients and is associated with an increased probability of lymph node metastases, and these patients are also more likely to have 24 positive nodes. We found no significant differences in terms of the proportion of patients with positive lymph nodes in ALND when comparing patients with and without ECE. Our results differ from other studies that showed a higher risk of non-sentinel lymph nodes metastases in patients with ECE>2mm. Conclussions: There is cumulative evidence on the role of ECE as a risk factor in breast cancer patients, and our findings further support this hypothesis. However, the extent of ECE is still a topic of heated debate, and its role in disease progression is less clear, given there are relatively few studies addressing this matter and there are discrepancies in the way the extent of ECE is measured. Considering recent publications where no significant differences were found in terms of longterm disease recurrence when stratifying patients according to the extent of ECE, our future endeavours should focus on the assessment of the course of the disease. To date, we have no evidence supporting the idea that patients with ECE<2mm could actually benefit from omis- sion of ALND.

Factores predictivos de alta carga residual ganglionar axilar post biopsia de ganglio centinela positiva / Predictive factors of high residual burden in axillary lymph node after positive sentinel node biopsy

El estado axilar es un factor pronóstico para los estadios tempranos de cáncer de mama. Existen factores que podrían predecir riesgo de mayor enfermedad axilar. El objetivo es determinar cuáles son los factores predictivos independientes de alta carga residual ganglionar axilar (4 o más GNC comprometidos) luego de la BGC positiva. Estudio analítico, observacional, cohorte retrospectiva de pacientes con tumores T1-2, axila clínicamente negativa, a las que se les realizó cirugía conservadora (CC) y BGC con resultado positivo (marco o micrometástasis) y se les realizó posterior linfadenectomía axilar (LA). Del total de 325 pacientes, 96 tuvieron resultado positivo para metástasis en el ganglio centinela (29,5%) y también se les realizó LA. Se dividió a la población seleccionada en dos grupos según el compromiso de los GNC: baja carga axilar 0-3 GNC positivos, y alta carga axilar 4 o más GNC positivos. Se observaron como factores que demostraron mayor riesgo para alta carga axilar ganglionar residual al grado histológico, ki-67 y la invasión extracapsular en el GC; pero solamente la invasión extracapsular en el GC demostró ser significativa en el análisis multivariado. Probablemente con un mayor número de pacientes otras variables pudieran haber resultado factores de riesgo independiente

Axillary status is a prognostic factor for early stages of breast cáncer. There are predictive factors that might indicate the risk of greater axilary disease. The aim is to determine which are the independent predictive factor sor a high residual axillary nodal burden (four or more non-sentinel lymph nodes involved) after a positive sentinel node biopsy. Retrospective cohort analytic observational study of patients with T1-2 tumors, negative axilla, who underwent breast conserving surgery and sentinel node biopsy with a positive result (macro ­ or micro-metastasis) and later underwent lymph node dissection. Out of the total 325 patients, 96 got a positive result for metástasis in the sentinel lymph node (29.5%) and also underwent lymph node dissection. The selected population was divided into two groups according to the involvement of NSLNs: low axillary burden: 0-3 NSLNs, and high axillary burden: 4 or more positive NSLNs. Among the factors found to have a higher risk of high residual axillary nodal burden were the histologic grade, Ki-67 and the extracapsular invasión of the SLN, but only the extracapsular invasión of the SLN was found to be significant in the multivariate analysis. It is likely that with a higher number of patients, other variables might have been independent risk factors

The value of multiparametric MRI for predicting prostate cancer extracapsular extension / 实用放射学杂志

Objective To evaluate the predictive value of multiparametric MRI (mpMRI)for extracapsular extension (ECE)in patients with prostate cancer.Methods The imaging of prostate mpMRI was performed in 52 consecutive patients with prostate cancer,who underwent subsequent radical prostatectomy.MR images were interpreted retrospectively by one experienced radiologist, who was blinded to any clinical details.According to Prostate Imaging Reporting and Data System Version 2 (PI-RADS v2),suspecious lesions were graded and recorded.Lesions with PI-RADS≥4 were further categorized in terms of ECE and correlated with radical prostatectomy pathology by using side-by-side comparison.Receiver operating characteristic (ROC)curves were used to calculate accuracy,sensitivity,specificity,positive predictive value(PPV)and negative predictive value(NPV),in order to evaluate diagnostic performance of ECE scoring system.Results Totally 55 prostate cancer foci with PI-RADS≥4 were correctly identified by the radiologist.The area under the ROC of ECE score was 0.694 (P=0.013)and ECE score 3 was considered as the best cutoff point with accuracy,sensitivity,specificity,PPV and NPV of 69.3%, 70.4%,67.9%,67.9% and 70.4%,respectively.Conclusion mpMRI is a relatively reliable noninvasive technique for assessment of ECE in clinical practice.

⁶⁸Ga-PSMA PET/CT Imaging Predicting Intraprostatic Tumor Extent, Extracapsular Extension and Seminal Vesicle Invasion Prior to Radical Prostatectomy in Patients with Prostate Cancer / 대한핵의학회잡지

PURPOSE: ⁶⁸Ga-labeled prostate-specific membrane antigen (PSMA) ligand positron emission tomography/computed tomography (PET/CT) has shown promising results in patients with biochemical recurrence after primary therapy for prostate cancer. In this study, we evaluated the usefulness of PSMA I&T (imaging and therapy) PET/CT prior to radical prostatectomy.METHODS: The study population consisted of 21 patients with prostate cancer who underwent ⁶⁸Ga-PSMA I&T PET/CT before either open or laparoscopic radical prostatectomy. Intraprostatic tumor extent, extracapsular extension (ECE) and seminal vesicle invasion (SVI) were assessed on the PET/CT scans. Tracer uptake was quantified in terms of standardized uptake values (SUVs). Imaging findings were correlated with final whole-gland histopathology.RESULTS: Of the 21 patients, two had T stage 2b disease, nine stage 2c, six stage 3a and four stage 3b. The median Gleason score was 7. The SUV(mean) of the primary tumors was 9.5 ± 8.8. SUV(mean) was higher in tumors with ECE than in organconfined tumors (13.8 ± 11.0 vs. 5.6 ± 3.2, p = 0.029). Peak tracer uptake was significantly positively correlated with Gleason score (r(s) = 0.49, p = 0.025). Sensitivity, specificity, positive predictive value and negative predictive value were, respectively, 94.7%, 75.0%, 97.3% and 60.0% for tumor infiltration of an individual prostate lobe, 75.0%, 100.0%, 100.0% and 97.4% for SVI, and 90.0%, 90.9%, 90.0% and 90.9% for ECE, using an angulated contour of the prostate as the criterion. Tumor volume derived from ⁶⁸Ga-PSMA I&T PET/CT was significantly correlated with preoperative prostate-specific antigen value (r(p) = 0.75, p < 0.001) and tumor volume on histopathology (r(p) = 0.45, p = 0.039).CONCLUSIONS: ⁶⁸Ga-PSMA I&T PET/CT prior to radical prostatectomy can contribute to presurgical local staging of prostate cancer. In this pilot study, ⁶⁸Ga-PSMA I&T PET/CT showed promising results for prediction of lobe infiltration, ECE and SVI.

Prostate-Specific Antigen Density as a Powerful Predictor of Extracapsular Extension and Positive Surgical Margin in Radical Prostatectomy Patients with Prostate-Specific Antigen Levels of Less than 10 ng/ml

PURPOSE: To assess the ability of preoperative variables to predict extracapsular extension (ECE) and positive surgical margin (PSM) in radical prostatectomy patients with prostate-specific antigen (PSA) levels of less than 10 ng/ml. MATERIALS AND METHODS: From January 2008 to December 2009, 121 patients with prostate cancer with PSA levels lower than 10 ng/ml who underwent radical prostatectomy were enrolled in the study. The differences in clinical factors (age, PSA, PSA density [PSAD], digital rectal examination [DRE] positivity, positive magnetic resonance imaging [MRI], Gleason sum, positive core number, and positive biopsy core percentage) with ECE and the presence of positive margins were determined and their independent predictive significances were analyzed. RESULTS: The ECE-positive patients had higher PSA, PSAD, and MRI-positive percentages, and PSM patients had higher PSA, PSAD, MRI-positive percentages, Gleason sum, and positive biopsy core percentages for prostate cancer. In the multivariate analysis, PSAD and MRI positivity were the best independent predictors for ECE, and PSA and PSAD were the best independent predictors of PSM. By receiver operating characteristic curve analysis, PSAD had better discriminative area under the curve value than did PSA for ECE (0.765 vs 0.661) and PSM (0.780 vs 0.624). The best predictive PSAD value was 0.29 ng/ml/cc for ECE and 0.27 ng/ml/cc for PSM. CONCLUSIONS: PSAD has relevance to ECE (plus MRI findings) and PSM (plus PSA). PSAD might be a powerful predictor of ECE and PSM preoperatively in patients undergoing a radical prostatectomy with PSA levels of less than 10 ng/ml.

The Prognostic Significance of Tumor Budding, Tumor Nodules, and Lymph Node Extracapsular Extension in Stage III Colorectal Cancer Patients

PURPOSE: The prognosis of advanced colorectal cancer patients may be different even for the same TNM staging. The characteristic features of tumors, such as tumor budding, tumor nodules, and extracapsular extension (ECE) of lymph nodes, can influence the disease progression and the outcome for patients. Tumor budding occurs what at the invasion front of colorectal adenocarcinomas, tumor cells, singly or in small aggregates, become detached from the neoplastic glands, and it can be divided it into two groups, low grade (0~16 foci in a field) and high grade (17 or more foci in a field). A tumor nodule is histologically identified within the fatty tissue or the detached fatty tissue around the dissected lymph nodes, or is a place picked up as lymph nodes from resected specimens which contain no lymph node components. ECE is defined as a tumor extension beyond the node capsule. The aims of this study were to evaluate the clinical significance of tumor budding, tumor nodules, and ECE of lymph nodes as prognostic factors in Stage III colorectal cancer patients. METHODS: We analyzed the disease-free and overall 5-year survival rates and recurrence rates in 94 Stage-III colorectal cancer patients according to tumor the budding intensity, the tumor nodules, and the lymph node ECE status. RESULTS: Of the entire group, the 5-year disease-free and overall survival rates were 49%, and 50%, respectively. The 5-year disease-free and overall survival rates were higher in the low-grade tumor budding group than in the high-grade group (58% vs 33%, P=0.045, 61% vs 39%, P=0.003). The 5-year disease-free and overall survival rates in patients with tumor nodules were lower than those in patients without one (44% vs 69%, P=0.086, 47% vs 77%, P=0.018). The recurrence rate was also higher in the group with tumor nodules than without one (80% vs 52%, P=0.045). The 5-year disease-free and overall survival rates were higher in the ECE negative group than in the positive one (68% vs 37%, P=0.018, 75% vs 42%, P=0.001). The recurrence rate was also higher in the ECE positive group than in the negative group (78% vs 46%, P=0.008). The existence of ECE and tumor nodule were strongly related to systemic recurrence (P=0.006, P=0.033), but not to the local recurrence (P=0.777, P=0.611). Considering the analysis of the recurrence pattern by N stage classification, there is no statistical difference in the N2 patient group, but there was in the existence of ECE and tumor nodule were strongly related to the systemic recurrence in N1 group (P=0.019, P=0.028). These three factors were scored according to the existence, and the score range was divided into two prognostic groups, high risk group (> or =2) and low risk group (<2). The high risk group was significantly associated with systemic recurrence (P= 0.004) rather than recurrence (P=0.865), and these score value were only significant in the N1 patient group (P=0.007) rather than in the N2 group (P=0.927). The high risk group also showed poor overall survival rate compared with the low risk one in only the N1 group (P=0.002), but nof in the N2 group (P=0.193). On multivariate analysis, UICC stage and ECE were two significant factors for tumor recurrence and the 5-year disease-free survival rate. CONCLUSIONS: These data showed that even if similar lymph node metastasis existed in advanced colorectal cancer patients, there was a different 5-year disease-free survival rate and overall survival rate according to the tumor budding, tumor nodule, and ECE status. On multivariate analysis, UICC stage and ECE were two significant factors for the tumor recurrence and the 5-year disease-free survival rate. Our results suggest that tumor budding, tumor nodule, and ECE of lymph node are excellent parameters to provide a confident prediction of clinical outcome.