Esophageal Cancer Staging System Research Articles

Development of a novel staging classification for Siewert II adenocarcinoma of the esophagogastric junction after neoadjuvant chemotherapy.

Stage classification for Siewert II adenocarcinoma of the esophagogastric junction (AEG) treated with neoadjuvant chemotherapy (NAC) has not been established. To investigate the optimal stage classification for Siewert II AEG with NAC. A nomogram was established based on Cox regression model that analyzed variables associated with overall survival (OS) and disease-specific survival (DSS). The nomogram performance in terms of discrimination and calibration ability was evaluated using the likelihood-ratio test, Akaike information criterion, Harrell concordance index, time-receiver operating characteristic curve, and decision curve analysis. Data from 725 patients with Siewert type II AEG who underwent neoadjuvant therapy and gastrectomy were obtained from the Surveillance, Epidemiology, and End Results database. Univariate and multivariate analyses revealed that sex, marital status, race, ypT stage, and ypN stage were independent prognostic factors of OS, whereas sex, race, ypT stage, and ypN stage were independent prognostic factors for DSS. These factors were incorporated into the OS and DSS nomograms. Our novel nomogram model performed better in terms of OS and DSS prediction compared to the 8th American Joint Committee of Cancer pathological staging system for esophageal and gastric cancer. Finally, a user-friendly web application was developed for clinical use. The nomogram established specifically for patients with Siewert type II AEG receiving NAC demonstrated good prognostic performance. Validation using external data is warranted before its widespread clinical application.

Effect of extracapsular lymph node involvement on the prognosis of patients with esophageal squamous cell carcinoma.

According to the eighth edition of the tumor node metastasis (TNM) staging system for esophageal cancer, it is recommended that extracapsular lymph node involvement (EC-LNI) is included as a registered independent variable for the disease. However, its role in the prognosis has not been clearly explained. To study the value of EC-LNI in the prognosis of esophageal cancer and attempt to explore its molecular mechanism via an enrichment analysis. A retrospective analysis was performed on 544 patients with esophageal squamous cell carcinoma (ESCC) who underwent radical surgery in the department of thoracic surgery of our hospital, focusing on the relationship between EC-LNI and clinicopathological characteristics and its effect on prognosis. Additionally, the mechanism of EC-LNI in esophageal cancer was explored. Among the 271 patients with lymph node metastasis, 125 were EC-LNI (+). The degrees of tumor differentiation, location, TNM stage, vascular tumor thrombus, and nerve invasion were related to the occurrence of EC-LNI. The stage of TNM was considered an independent risk factor for the development of EC-LNI. A significant difference was found in terms of overall survival (OS) and disease-free survival (DFS) between the EC-LNI (+) and EC-LNI (-) groups. A univariate analysis showed that the degrees of tumor differentiation, T stage, N stage, TNM stage, EC-LNI, EC-LNI number, and EC-LNI distance were significantly correlated with prognosis. A multivariate survival analysis showed that tumor differentiation, TNM stage, and EC-LNI were independent prognostic factors for OS, while TNM stage and EC-LNI were independent prognostic factors for DFS. The enrichment analysis identified the molecular targets and signaling pathways that can regulate cell proliferation, differentiation, and apoptosis. Extracapsular LNI has a high prognostic value in patients with esophageal cancer and is closely related to the stage of tumors. Our preliminary molecular mechanism research indicated that the molecular targets of EC-LNI are expected to become a new direction for the treatment of esophageal cancer.

Optimal Size Criterion for Malignant Lymph Nodes and a Novel Lymph Node Clinical Staging System for Unresectable Esophageal Squamous Cell Carcinoma: Evaluation by Multislice Spiral Computed Tomography.

Objectives: The current Chinese draft nodal clinical staging system for unresectable esophageal cancer is controversial. Our study aimed to propose a new diagnostic criterion for lymph node metastasis (LNM) detected by multislice spiral computed tomography (MSCT) in nonsurgically treated esophageal squamous cell carcinoma (ESCC) patients and then develop a novel lymph node (LN) clinical staging system for better individual prognostic prediction.Methods: The short-axis diameters of regional LNs were measured in 393 nonsurgical patients. Regional nodes were considered positive for malignancy if the nodal size exceeded the optimal size, which was determined by Kaplan-Meier survival analysis. The novel LN clinical staging system was then constructed using the LASSO model based on the relative prognostic importance of different LN stations. Validation cohort was included to confirm the prognostic performance.Results: Regional nodes were considered positive for malignancy if they were larger than 10 mm in the low cervical and upper thoracic segments, 7 mm in the middle thoracic segment, and 8 mm in the lower thoracic and celiac segments. Using the LASSO model, stations 2R, 3A, 7 and 16 were qualified in the model. Further analysis showed that our LN clinical staging system had better homogeneity, discriminatory ability and clinical value than the draft nodal staging system.Conclusions: Our results show that the new diagnostic criterion may improve the diagnostic value of MSCT in metastatic LNs. The novel LN clinical staging system can stratify nonsurgically treated ESCC patients into different risk groups, providing valuable information for decision making and outcome prediction.

Comparison of the prognostic difference between ypTNM and equivalent pTNM stages in esophageal squamous cell carcinoma based on the 8th edition of AJCC classification.

Objective: With the separate ypTNM stage groupings established in the 8th edition of AJCC staging system for esophageal squamous cell cancer (ESCC), we aimed to evaluate the prognostic difference between ypTNM stage and equivalent pTNM stage.Methods: ESCC patients with surgery alone (cohort 1) and patients with neoadjuvant therapy plus surgery (cohort 2) were enrolled in the study.Results: In p0, pIb, pIIa, pIIb, pIIIa, pIIIb and pIVa stages of cohort 1, the 5-year DFS and OS rates were 100/100%, 80.5/86.2%, 58.9/57.8%, 51.1/52.7%, 36.3/35.8%, 21.5/22.6% and 11.9/18.0%. In ypI, ypII, ypIII and ypIVa stages of cohort 2, the 5-year DFS and OS rates were 60.9/67.0%, 44.3/52.1%, 48.4/43.2% and 0. Patients in ypI stage had a tendency of poorer survival compared with those in pI stage (P=0.024 for DFS, P=0.067 for OS). There was no significant difference in terms of DFS (P=0.335) or OS (P=0.903) between ypII and pII. Patients in ypIII stage had a tendency of better survival compared with those in pIII stage (P=0.015 for DFS, P=0.059 for OS). Patients in ypIVa stage exhibited a significantly poorer OS compared with those in pIVa stage (P=0.038).Conclusions: With down-staged tumor after neoadjuvant therapy, survival of ypI was closed but not reached to the prognosis of equivalent pI, prognosis of ypII was similar to equivalent pII, and survival of ypIII tended to be better compared with equivalent pIII. However, without down-staged ypIVa tumor, the prognosis was worse compared with equivalent pIVa, indicating those patients were primary resistant to prescribed neoadjuvant therapy.

Application of the proposed eighth edition of the American Joint Committee on Cancer/Union of International Cancer Control esophageal cancer staging system in esophageal cancer patients

AbstractObjectiveThe eighth edition of the American Joint Committee on Cancer/Union of International Cancer Control esophageal cancer staging system was proposed in early 2018. The eighth edition staging system includes clinical staging, pathological staging, and neoadjuvant pathological staging, which fills in the blank of non‐operative staging of esophageal cancer. However, there are few reports on the eighth edition of clinical staging, and the purpose of the present study was to verify the prognostic value of the new American Joint Committee on Cancer clinical staging system for esophageal cancer patients who undergo radical radiation therapy.MethodsA total of 544 patients with esophageal cancer from Tianjin Medical University Cancer Institute and Hospital between March 2010 and September 2016 were staged according to the eighth American Joint Committee on Cancer clinical staging system. The Kaplan–Meier method was used to calculate the survival rate of the patients. The Cox regression model was used for multivariate prognostic analysis.ResultsAll the patients were divided into different groups by the eighth American Joint Committee on Cancer clinical tumor–node–metastasis staging system: 40 patients with T2; 157 patients with T3; 347 patients with T4; 132 patients with N0; 193 patients with N1; 172 patients with N2; 47 patients with N3; 81 patients with stage II; 102 patients with state III; and 361 patients with stage IVA. The 3‐year survival rates of stage T2, stage T3, and stage T4 were 60.1%, 45.6%, and 30.8%, respectively (P < 0.001). The 3‐year survival rates of stage N0, stage N1, stage N2, and stage N3 were 48.2%, 40.7%, 29.4%, and 17.3%, respectively (P < 0.001). The 3‐year survival rates of stage II, stage III, and stage IVA were 59.3%, 40.1%, and 31.2%, respectively (P < 0.001). In univariate analysis, age, concurrent chemoradiotherapy, T stage, N stage, Karnofsky marking system, the sixth edition staging system and the eighth edition staging system were important prognostic factors in univariate analyses. In multivariate analysis, concurrent chemotherapy and N stage were important prognostic factors.ConclusionsBased on the data from Tianjin Medical University Cancer Institute and Hospital, the eighth edition clinical staging system had a better predictive ability for esophageal cancer patients who underwent radical radiation therapy.

Su1121 – M1A Disease Should Be Reconsidered in Esophageal Cancer Staging System from the Prespective of Treatment Response and Survival After Definitive Concurrent Chemoradiotherapy

Su1121 – M1A Disease Should Be Reconsidered in Esophageal Cancer Staging System from the Prespective of Treatment Response and Survival After Definitive Concurrent Chemoradiotherapy

Proposed revision of the 8th edition AJCC clinical staging system for esophageal squamous cell cancer treated with definitive chemo-IMRT based on CT imaging

PurposeTo validate and propose revision of the 8th edition American Joint Committee on Cancer (AJCC) clinical staging system for esophageal squamous cell cancer (ESCC) patients treated with definitive intensity-modulated radiation therapy combined with concurrent chemotherapy (Chemo-IMRT) based on computed tomography (CT) imaging.MethodsThe clinical data of patients with ESCC treated with Chemo-IMRT were collected and retrospectively reviewed. All CT images were independently reevaluated and restaged according to the 8th edition AJCC staging system. The overall survival (OS) rates were analyzed statistically. ROC curves of the various parameters of the primary tumor and metastatic lymph nodes were generated in order to identify the cutoff values correlated to patient survival using the area under curve.ResultsThe gross tumor volume of the primary tumor (GTV-prT) and the clinical N stage (cN) were independent factors that influenced OS. The 5-year OS rate of patients with GTV-prT ≤28 cm3, GTV-prT > 28 and ≤ 56 cm3, and GTV-prT > 56 cm3 were 54.6, 31.1 and 18.6%, respectively. The 5-year OS rate of patients with cN0, cN1 SLNM (−), cN2 SLNM (−), cN3 SLNM (−) and SLNM (+) were 62.8 (P < 0.001), 34.0 (P = 0.16), 20.0 (P = 0.785), 0 (P < 0.001) and 26.9%, respectively. After restaging the SLNM as regional MLNs, the 5-year OS rates of the patients with cN0, 1, 2 and 3 were 62.8, 36.3, 23.7 and 7.8%, respectively. Various GTV-prT were combined with the cN to establish a new clinical TNM staging system: I, GTV-prT1 and cN0; II, GTV-prT2 or 3 and cN0, GTV-prT1 and cN1; III, GTV-prT1 and cN2, GTV-prT2 and cN1,2; Iva, GTV-prT3 and cN1,2; IVb, GTV-prTany and cN3; IVc, TanyNanyM1. Subsequently, the OS differed significantly between the adjacent GTV-prT cN categories, except those of stage I vs. II.ConclusionThe SLNM should be dealt with as a regional rather than a distant disease in patients with ESCC when treated with CRT. The proposed nonsurgical staging system based on the GTV-prT and N appears to be a simple and accurate prognosis predictor for patients with ESCC who have undergone definitive Chemo-IMRT.

M1a disease should be reconsidered in esophageal cancer staging system from the perspective of treatment response and survival after definitive concurrent chemoradiotherapy.

13 Background: M1a node involvement based on the 6th edition AJCC staging system was classified as regional node involvement in the 7th edition of esophageal squamous cell carcinoma (ESCC). However, the clinical significance of M1a node involvement based on the 6th edition staging system has not been well established. Thus, we analyzed the prognostic value of M1a node in patients of ESCC after definitive chemoradiotherapy (CCRT). Methods: A total of 188 ESCC patients had M0 disease based on the 7th edition AJCC classification, of which 31 (16.5%) of them were reclassified to the M1a patient group under the 6th edition AJCC classification. After definitive CCRT, we compared the basic characteristics of two groups, analyzed the rate of complete remission (CR), recurrence, finally assessed overall survival (OS), and disease-free survival (DFS) of each group. Results: Among 31 patients reclassified to M1a disease, 21 patients (67.7%) had subclavian nodes and 10 patients (32.3%) had celiac nodes. The median follow-up period was 18.3 months. The M1a group showed a significantly lower survival rate not only in median OS (M1a 16.4 months, M0 42.7 months, P = 0.015), but also in 5-year OS (M1a 10.8%, M0 41.2%). Three of 31 patients (9.7%) in the M1a group achieved CR, while 41 of 157 patients (26.1%) in the M0 group achieved CR ( P = 0.048). However, there was no recurrence in the M1a group after achieved CR during follow-up period. Conclusions: Among ESCC patients after completing definitive CCRT, M1a patients according to the 6th AJCC staging system showed lower CR rate and OS rate compared with M0 disease patients. M1a nodes should be differentiated from regional node involvement.

ASO Author Reflections: It is Essential to Explore More Accurate Nodal Staging System for Esophageal Cancer.

ASO Author Reflections: It is Essential to Explore More Accurate Nodal Staging System for Esophageal Cancer.

Proposed revision of N categories to the 8th edition of the AJCC-TNM staging system for non-surgical esophageal squamous cell cancer.

The 8th edition of the American Joint Committee on Cancer Tumor‐Node‐Metastasis (AJCC‐TNM) staging system for esophageal cancer (EC) retained the definition of N categories based on the number of metastatic lymph nodes (LN). However, it is difficult to accurately determine the number of metastatic LN without surgery. This study aimed to propose a revision to the N categories of the 8th edition AJCC‐TNM staging system that makes staging easier to perform and better represents the prognosis of non‐surgical esophageal squamous cell cancer (ESCC). We retrospectively reviewed the data of 336 patients with ESCC. The revised N categories were based on the anatomic regions of LN metastasis (cervix, thorax and abdomen). Survival was analyzed using the Kaplan‐Meier method and compared using the log‐rank test. Multivariate analyses were performed using the Cox proportional hazard model. Survival differences were adequately discriminated when the revised N categories were used. Subgroup analyses by T stage showed significant difference in overall survival between the revised N categories. Multivariate analyses demonstrated that T stage, revised N category, age, sex and treatment modality were independent risk factors, with the revised N category being the most significant variable. The revised N categories determined in this study can be used to fill gaps in the staging system for patients with non‐surgical ESCC, which can help clinicians to make better treatment decisions and more effectively predict patient prognoses. Future large‐scale studies are required to validate these results.

Is the new distribution of early esophageal adenocarcinoma stages improving the prognostic prediction of the 8th edition of the TNM staging system for esophageal cancer?

The 8th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging system released in 2017 reclassified the pTNM stage of early esophageal adenocarcinoma from stage IA in the 7th edition to stage IA and IB and from stage IB in the 7th edition to stage IC. In this study, we analyzed the reliability of the new staging system through clinical data analysis. We selected patient data from the Surveillance, Epidemiology, and End Results (SEER) database. From 2004 to 2014, data for a total of 714 patients were included in the study and were divided into groups representing stage IA (n=84), IB (n=386) and IC (n=244) according to the 8th edition. In the 8th edition, there was no significant difference between groups IA and IB in overall survival (OS) (P=0.331) or esophageal cancer-specific survival (ECSS) (P=0.341). However, the long-term survival rates of groups IA and IB were significantly higher than those of group IC. Cox regression analysis indicated that the use of new staging system does not affect prognosis. We also attempted to stratify the tumors by T stage and histological grade but found no significant difference. We used the SEER database to compare the staging of early esophageal adenocarcinomas between the 8th and 7th editions of the AJCC/UICC TNM staging system. Based on our data, the 8th edition is not superior to the 7th edition.

Validation of the eighth clinical American Joint Committee on Cancer stage grouping for esophageal cancer.

To validate the American Joint Committee on Cancer (AJCC) clinical staging system for esophageal cancer using Surveillance, Epidemiology and End Results database. Cancer-specific survival analyses for clinically-staged patients with esophageal cancer according to both seventh and eighth editions were conducted through Kaplan-Meier analysis. For cancer-specific survival according to both seventh and eighth clinical systems, p-values for pairwise comparisons were nonsignificant in many comparisons. C-index for adenocarcinoma was: 0.671 according to the seventh AJCC and 0.671 according to the clinical eighth AJCC. C-index for squamous cell carcinoma according to the seventh AJCC was: 0.634 and 0.643 according to clinical eighth AJCC. Minimal improvement was achieved by the eighth clinical AJCC staging system for esophageal cancer.

Comparison of the prognostic value of the seventh and eighth edition of The AJCC Esophageal Cancer Staging System for the patients with stage Ⅱ and Ⅲesophageal squamous cell carcinoma

Objective: To compare and evaluate the prognostic value of the 7(th) and 8(th) edition of The AJCC Esophageal Cancer Staging System for patients with stage Ⅱ and Ⅲ esophageal squamous cell carcinoma. Methods: The clinical data of 328 esophageal cancer patients who received operation at Department of Esophageal Cancer, Tianjin Tumour Hospital from January 2006 to December 2010 were restrospectively analyzed. There were 63 female and 265 male patients. The mean age was 65 (range: 33 to 87) years. Univariate and multivariate analysis were performed to identify the prognosis factors. Results: The five years overall survival rates among patients with stage Ⅱ and Ⅲ were both significantly different (χ(2)=87.035, 84.730, all P=0.000) according to the 7(th) and 8(th) editions of the TNM staging systems. The five years overall survival rate among patients with stage ⅡB and ⅢA were significantly different (39.6% vs 23.4%, P=0.001) according to the 7(th) edition of the esophageal cancer staging systems.According to the 8(th) edition of the esophageal cancer staging system, the 5 years survival rate of patients with stage ⅡA and ⅡB, ⅢB and Ⅳ was statistically significant (58.5% vs. 35.5%, P=0.040; 18.9% vs. 0, P=0.000). In multivariate analysis, tumor size, T staging, N staging and tumor differentiation (HR=1.592, 95%CI: 1.185 to 2.139, P=0.002; HR=1.519, 95% CI: 1.236 to 1.867, P=0.000; HR=1.647, 95% CI: 1.448 to 1.874, P=0.000; HR=1.404, 95% CI: 1.059 to 1.861, P=0.018) were the main independent prognosis factors affecting the prognosis of esophageal squamous cell carcinoma patients. Conclusions: Both the 7(th) and the 8(th) editions of TNM staging systems are able to reflect the clinical prognosis of patients receiving radical resection of esophageal cancer, and the factors of tumor size, differentiaton, invasion depth and lymph node metastases are the independent predictors of prognosis. The 8(th) edition provides a more detailed and more reasonable for the staging of stage Ⅱ and Ⅲ for esophageal cancer patients than the 7(th) edition, and it is more accurate for the prognosis of patients with esophageal cancer after surgery.

Discussion of N staging category of the eighth edition of The AJCC Esophageal Cancer Staging System

AJCC Esophageal Cancer Staging System, 8(th) edition will be implemented on January 1, 2018. The N staging in 8(th) edition of staging system remains following 7(th) edition based on the number of metastatic nodes, except the limited revision of the regional lymph node map. N staging revision was reviewed from the simple definition of negative (N0) and positive (N1) lymph node(s) to the positive node number based proposal (7(th) edition). The 7(th) edition staging system, especially the N staging, were proved with more advantages on distinguishing disease progression and predicting prognosis of the esophageal cancer. On other hand, the disadvantages of 7(th) edition N staging are discussed. The refined N staging based on the number of metastatic node station is introduced. The extent and station of metastatic node could better reflect the disease progression and prognosis according to our research. The controversy on N staging of esophagogastric junction cancer is discussed as well. Other reported N staging associated index including lymph node ratio, lymphatic vessel invasion and biomarkers are reviewed and evaluated.

Interpretation of update on The AJCC Esophageal Cancer Staging System, Eighth Edition

The recently published AJCC Esophageal Cancer Staging System, 8(th) Edition will be implemented on Januray 1, 2018, which was developed by Worldwide Esophageal Cancer Collaboration based on 22 654 esophageal cancer patients from 33 worldwide centers. The definition of T, N, M, G stage and regional lymph nodes were optimized in the 8(th) edition. And the new "2 cm" principle has simplified the definition for the cancer of esophagogastric junction. In addition to pathologic staging, the 8(th) edition also provided clinical staging and pathologic staging after neoadjuvant therapy, making the new esophageal cancer staging system more practicable and reasonable.

Assessment of Lymph Node Ratio to Replace the pN Categories System of Classification of the TNM System in Esophageal Squamous Cell Carcinoma

IntroductionThe seventh edition of the TNM staging system for esophageal cancer outlined by the American Joint Committee on Cancer (AJCC) defines the N classification on the basis of the number of metastatic lymph nodes. However, this classification is dependent on the actual number of examined lymph nodes. Here in this study, we have focused on revising this N classification system with the metastatic lymph nodes ratio (LNR) and also assessing whether this modification to the current AJCC staging system can better define the prognostic characteristics of esophageal squamous cell carcinoma (ESCC). MethodsWe retrospectively reviewed 916 patients with ESCC who underwent curative resection. Prognostic performance of two staging systems was compared using the Akaike information criterion value and receiver operating characteristics curve. In addition, decision curve analysis evaluated the clinical practical usefulness of the prediction models by quantifying their net benefits. ResultsThe univariate and multivariate Cox regression analyses indicated that LNR was an independent risk factor for overall survival. The modified staging system based on LNR had better discriminatory ability, monotonicity, homogeneity, and stratification than the TNM staging system in determining the prognosis of patients with ESCC. However, the decision curves analysis suggested that the modified staging based on LNR has poor clinical practical value over the AJCC TNM staging system. ConclusionsLNR can supplement the pN categorization system for more effective evaluation of prognosis. But the modified staging system based on LNR has a poor clinical practical value for patients with ESCC compared with the current TNM system and is not superior to AJCC pN staging for ESCC.

Endoscopic Tumor Length Should Be Reincluded in the Esophageal Cancer Staging System: Analyses of 662 Consecutive Patients.

Esophageal cancer represents the 6th cause of cancer mortality in the World. New treatments led to outcome improvements, but patient selection and prognostic stratification is a critical aspect to gain maximum benefit from therapies. Today, patients are stratified into 9 prognostic groups, according to a staging system developed by the American Joint Committee on Cancer. Recently, trying to better select patients with curing possibilities several authors are reconsidering tumor length as a valuable prognostic parameter. Specifically, endoscopic tumor length can be easily measured with an esophageal endoscopy and, if its utility in esophageal cancer staging is demonstrated, it may represent a simple method to identify high risk patients and an easy-to-obtain variable in prognostic stratification. In this study we retrospectively analyzed 662 patients treated for esophageal cancer, stratified according to cancer histology and current staging system, to assess the possible role of endoscopic tumor length. We found a significant correlation between endoscopic tumor length, current staging parameters and 5-year survival, proving that endoscopic tumor length may be used as a simple risk stratification tool. Our results suggest a possible indication for preoperative therapy in early stage squamocellular carcinoma patients without lymph nodes involvement, who are currently treated with surgery alone.

International Multicenter Study on the Impact of Extracapsular Lymph Node Involvement in Primary Surgery Adenocarcinoma of the Esophagus on Overall Survival and Staging Systems.

The current pathological lymph node (pN) staging is based on the number of positive lymph nodes but does not take into consideration characteristics of the involved lymph nodes itself. The current study aims to examine the prognostic value of extracapsular lymph node involvement (EC-LNI) and intracapsular lymph node involvement (IC-LNI) for esophageal adenocarcinoma treated by primary surgery. From the databases of five European high volume centers, 1639 adenocarcinoma patients with primary R0-resection were withheld after excluding 90-day mortality. Oncologic variables, including number of resected lymph nodes, number of resected positive lymph nodes, and EC-LNI/IC-LNI were examined. The Union Internationale contre le Cancer (UICC) 7th edition prognostic staging was used as baseline staging system. Statistical analysis was performed by Cox proportional hazards modeling and verified using the Random Survival Forest technique. EC-LNI showed significantly worse overall 5-year survival compared with IC-LNI overall (13.4% vs 37.2%, P < 0.0001), including in each pN-category [16.4% vs 45.6% in pN1 (P < 0.0001), 16.1% vs 23.8% (P = 0.047) in pN2 (P = 0.065), and 8.7% vs 26.3% in pN3 categories, respectively]. pN1 IC-LNI patients show a 5-year overall survival comparable (P = 0.92) with stage IIB (ie, pT3N0). Reclassifying the UICC prognostic stages according to these findings into an adapted staging model showed a significant (P < 0.0001) increase in homogeneity, discriminatory ability, and monotonicity compared with the original UICC TNM 7th edition prognostic staging. These data suggest that lymph node capsular status is an important prognostic factor and should be considered for the future edition of the TNM staging system for esophageal cancer.

Proposed Modification of Nodal Staging as an Alternative to the Seventh Edition of the American Joint Committee on Cancer Tumor-Node-Metastasis Staging System Improves the Prognostic Prediction in the Resected Esophageal Squamous-Cell Carcinoma

The 7th American Joint Committee on Cancer (AJCC) tumor-node-metastasis staging system for esophageal cancer defined N classification based on the number of metastatic lymph nodes (LNs). However, this classification might neglect the extent of LNs metastasis. This study aimed to revise N classification based on the extent of LNs metastasis and propose a modification to the current AJCC staging system for better representing the prognostic characteristics of Chinese esophageal squamous-cell carcinoma (ESCC). We retrospectively reviewed 1993 ESCC patients who underwent curative resection. The proposed N categories based on the number of LNs metastasis stations were compared with the current staging system by univariate and multivariate Cox regression analyses. Homogeneity, discriminatory ability, and monotonicity of gradients of two staging systems were compared using likelihood ratio χ statistics and Akaike information criterion calculations. The survival differences were not significant for N2 versus N3 category (p = 0.231) and stages IIIB versus IIIC (p = 0.713) based on the 7th AJCC staging system. When the modified staging system was adopted, the survival difference for N2 versus N3 and IIIB versus IIIC could be well discriminated. Statistical analysis showed that the modified staging system had higher likelihood ratio χ scores and smaller Akaike information criterion values than the 7th AJCC staging system, which represented the optimum prognostic stratification. The modified staging system with the revised N categories based on the number of LNs metastasis stations better predicts the survival of Chinese ESCC population than the 7th AJCC staging system. Further studies are required to confirm this result.

How well does pathologic stage predict survival for esophageal adenocarcinoma after neoadjuvant therapy?

Cancer staging systems are designed to predict survival and stratify patients. The 7(th) edition of the American Joint Commission on Cancer (AJCC7) staging system for esophageal cancer was modeled using survival data on patients who underwent esophagectomy without induction or adjuvant therapy. In the United States, the standard of care for patients with locally advanced tumors often includes neoadjuvant therapy. The prognostic value of the pathologic stage for these patients is unknown. Data from the Surveillance Epidemiology and End Results (SEER) were used to identify 1,243 patients with adenocarcinoma of the esophagus who underwent surgery after neoadjuvant therapy from 1988-2009. Included in the analysis were pathologically-staged, non-metastatic patients who had radiation as part of their neoadjuvant therapy. The AJCC7 staging system and an alternate system were modeled using Kaplan-Meier survival methods. The two systems were compared using log-rank chi-squared statistics, with large chi-squared values indicating accuracy in survival prediction. The AJCC staging system was able to predict survival for patients who had neoadjuvant therapy (P<0.001, chi-squared =81.8); however, there was little distinction between stage subgroups. Patients with neoadjuvant radiotherapy had improved survival for pathologic stage II and III disease. An alternative, simpler staging system was better able to stratify patients with neoadjuvant therapy (P<0.001, chi-squared =100.5). The current AJCC staging system is able to predict survival in esophageal adenocarcinoma patients undergoing neoadjuvant therapy, however, there is less distinction among stage subgroups. An alternative, simpler stage grouping may better stratify patients receiving neoadjuvant therapy.