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Liatsou E, Bellos I, Katsaros I, Michailidou S, Karela NR, Mantziari S, Rouvelas I, Schizas D. Sex differences in survival following surgery for esophageal cancer: A systematic review and meta-analysis. Dis Esophagus 2024; 37:doae063. [PMID: 39137391 DOI: 10.1093/dote/doae063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 06/25/2024] [Accepted: 08/03/2024] [Indexed: 08/15/2024]
Abstract
The impact of sex on the prognosis of patients with esophageal cancer remains unclear. Evidence supports that sex- based disparities in esophageal cancer survival could be attributed to sex- specific risk exposures, such as age at diagnosis, race, socioeconomic status, smoking, drinking, and histological type. The aim of our study is to investigate the role of sex disparities in survival of patients who underwent surgery for esophageal cancer. A systematic review and meta-analysis of the existing literature in PubMed, EMBASE, and CENTRAL from December 1966 to February 2023, was held. Studies that reported sex-related differences in survival outcomes of patients who underwent esophagectomy for esophageal cancer were identified. A total of 314 studies were included in the quantitative analysis. Statistically significant results derived from 1-year and 2-year overall survival pooled analysis with Relative Risk (RR) 0.93 (95% Confidence Interval (CI): 0.90-0.97, I2 = 52.00) and 0.90 (95% CI: 0.85-0.95, I2 = 0.00), respectively (RR < 1 = favorable for men). In the postoperative complications analysis, statistically significant results concerned anastomotic leak and heart complications, RR: 1.08 (95% CI: 1.01-1.16) and 0.62 (95% CI: 0.52-0.75), respectively. Subgroup analysis was performed among studies with <200 and > 200 patients, histology types, study continent and publication year. Overall, sex tends to be an independent prognostic factor for esophageal carcinoma. However, unanimous results seem rather obscure when multivariable analysis and subgroup analysis occurred. More prospective studies and gender-specific protocols should be conducted to better understand the modifying role of sex in esophageal cancer prognosis.
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Affiliation(s)
- Efstathia Liatsou
- Department of Clinical Therapeutics, Alexandra General Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
| | - Ioannis Bellos
- Department of Hygiene, Epidemiology and Medical Statistics, National and Kapodistrian University of Athens, Medical School, Athens, Greece
| | - Ioannis Katsaros
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Styliani Michailidou
- First Department of Paediatric Surgery, Panagiotis & Aglaia Kyriakou Children's Hospital, Athens, Greece
| | - Nina-Rafailia Karela
- Second Department of Internal Medicine, Elpis General Hospital of Athens, Athens, Greece
| | - Styliani Mantziari
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland
| | - Ioannis Rouvelas
- Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden; Department of Upper Abdominal Surgery, Karolinska University Hospital, Stockholm, Sweden
| | - Dimitrios Schizas
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
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Potdar A, Chen KC, Kuo SW, Lin MW, Liao HC, Huang PM, Lee YH, Wang HP, Han ML, Cheng CH, Hsu CH, Huang TC, Hsu FM, Lu SL, Lee JM. Prognostication and optimal criteria of circumferential margin involvement for esophageal cancer after chemoradiation and esophagectomy. Front Oncol 2023; 13:1111998. [PMID: 37503328 PMCID: PMC10369182 DOI: 10.3389/fonc.2023.1111998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 06/09/2023] [Indexed: 07/29/2023] Open
Abstract
Purpose Circumferential radial margin (CRM) involvement by tumor after resection for esophageal cancer has been suggested as a significant prognostic factor. However, the prognostic value of CRM involvement after surgery with neoadjuvant concurrent chemoradiotherapy (CCRT) is unclear. This study aimed to evaluate the prognostic value of and survival outcomes in CRM involvement as defined by the Royal College of Pathologists (RCP) and the College of American Pathologists (CAP) for patients with esophageal cancer undergoing neoadjuvant CCRT and esophagectomy. Methods A total of 299 patients with esophageal cancer who underwent neoadjuvant CCRT followed by esophagectomy between 2006 and 2016 were enrolled in our study. The CRM status of the specimens obtained was determined pathologically according to both the CAP and RCP criteria. Survival analyses were performed and compared according to the two criteria. Results Positive CRM was found in 102 (34.1%) and 40 (13.3%) patients according to RCP and CAP criteria, respectively. The overall and progression-free survival rates were significantly lower in the CRM-positive group than in the CRM-negative group according to both the RCP and CAP criteria. However, under multivariate analysis, in addition to pathological T and N staging of the tumor, only CAP-defined CRM positivity was a significant prognostic factor with adjusted hazard ratios of 2.64 (1.56-4.46) and 2.25 (1.34-3.78) for overall and progression-free survival, respectively (P < 0.001). Conclusion In patients with esophageal cancer undergoing neoadjuvant CRT followed by esophagectomy, CAP-defined CRM positivity is an independent predictor of survival. Adjuvant therapy should be offered to patients with positive CRM.
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Affiliation(s)
- Ankit Potdar
- Department of Gastroenterology, Global Hospital, Mumbai, India
- Division of Thoracic Surgery, Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ke-Cheng Chen
- Division of Thoracic Surgery, Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Shuenn-Wen Kuo
- Division of Thoracic Surgery, Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Mong-Wei Lin
- Division of Thoracic Surgery, Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Hsien-Chi Liao
- Division of Thoracic Surgery, Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Pei-Ming Huang
- Division of Thoracic Surgery, Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yi-Hsuan Lee
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
| | - Hsiu-Po Wang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Ming-Lun Han
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chia-Hsien Cheng
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
| | - Chih-Hung Hsu
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
| | - Ta-Chen Huang
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
| | - Feng-Ming Hsu
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
| | - Shao-Lun Lu
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
| | - Jang-Ming Lee
- Division of Thoracic Surgery, Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
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Proposed Modification of the pN2 Classification of the 8th Edition AJCC Staging System for Esophageal Squamous Cell Carcinoma: A Preliminary Study Based on the Chinese Population. JOURNAL OF ONCOLOGY 2021; 2021:8871884. [PMID: 33777143 PMCID: PMC7972858 DOI: 10.1155/2021/8871884] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 01/24/2021] [Accepted: 02/08/2021] [Indexed: 11/17/2022]
Abstract
Objective To evaluate the efficacy of the nodal staging of the 8th edition AJCC staging system for esophageal squamous cell carcinoma (ESCC) and propose a modification of the current pN2 classification. Methods 1188 patients who underwent esophagectomy for ESCC at Sun Yat-sen University Cancer Center in Guangzhou (Guangdong, China) between January 2005 and June 2010 were reviewed. We used the X-tile software to determine the optimal cutoff points. Kaplan–Meier method and log-rank test were used to compare the differences of survival. Multivariate Cox regression analysis was performed for the factors that were statistically significant in univariate analysis. Result In multivariate Cox regression analysis, alcohol consumption, pT status, and pN status were independent prognostic factors for overall survival (OS) according to the current pN classifications. And the observed 5-year OS rates for groups pN0, pN1, pN2, pN3 were 66.7%, 45.0%, 31.5%, and 21.5%, respectively (P<0.001). Based on the above results, the current pN2 classification was further subdivided as pN2a [3 metastatic lymph nodes (LNs)] and pN2b (4−6 metastatic LNs) groups. The 5-year OS rates for groups pN0, pN1, pN2a, pN2b, and pN3 were 66.7%, 45.0%, 37.7%, 26.3% and 21.5%, respectively (P<0.001). The rate of 5-year disease-free survival (DFS) was 60.0% for patients with pN0, compared with 36.8%, 29.3%, 20.8%, and 14.3% for those with pN1, pN2a, pN2b, and pN3, respectively (P<0.001).The current pN2 classification should be subdivided as pN2a (3 metastatic LNs) and pN2b (4–6 metastatic LNs) groups. The modified pN2 classification could better discriminate the survival differences between patients with 3–6 metastatic LNs for ESCC in the Chinese population.
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Askari A, Munster AB, Jambulingam P, Riaz A. Critical number of lymph node involvement in esophageal and gastric cancer and its impact on long-term survival-A single-center 8-year study. J Surg Oncol 2020; 122:1364-1372. [PMID: 32803769 DOI: 10.1002/jso.26145] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 07/22/2020] [Indexed: 12/25/2022]
Abstract
BACKGROUND Nodal disease in esophageal and gastric cancer is associated with poor survival. OBJECTIVES To determine the critical level of lymph node involvement where survival becomes significantly compromised. METHODS Survival analyses using multivariable Cox regression and receiver operator characteristics (ROC) were undertaken to determine what number of positive lymph nodes were most sensitive and specific in predicting survival. RESULTS A total of 317 patients underwent esophagectomy (n = 190, 59.9%) and gastrectomy (n = 127, 40.1%) for adenocarcinoma. At multivariable analyses, four nodes positivity (irrespective of T-category) was associated with nearly a fivefold increased risk of mortality when compared to node-negative patients (hazard ratio [HR], 4.9; interquartile range 2.0-11.5; P < .001). A positive ratio of up to 50.0% was not associated with worse survival than having four nodes positive (HR, 4.6; 95% confidence interval, 2.6-8.1; P < .001). ROC analysis demonstrated four lymph nodes positive to have a sensitivity of 80.5%, a specificity of 60.1%, and an accuracy of 77.8 (P < .001). CONCLUSION The absolute number of nodes positive for cancer is more important than the proportion of positive nodes in predicting survival in esophageal/gastric cancer. Four positive lymph nodes are associated with a fivefold increase in mortality. Beyond this, increasing numbers of positive lymph nodes make no appreciable difference to survival.
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Affiliation(s)
- Alan Askari
- Department of Surgery, West Hertfordshire Hospitals NHS Trust, Watford, UK
| | - Alex B Munster
- Department of Surgery, West Hertfordshire Hospitals NHS Trust, Watford, UK
| | | | - Amjid Riaz
- Department of Surgery, West Hertfordshire Hospitals NHS Trust, Watford, UK
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Zhao Z, Zhang Y, Wang P, Wang X, Li M. The impact of the nodal status on the overall survival of non-surgical patients with esophageal squamous cell carcinoma. Radiat Oncol 2019; 14:161. [PMID: 31481064 PMCID: PMC6724275 DOI: 10.1186/s13014-019-1365-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Accepted: 08/21/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The prognosis of N categories for patients with non-surgical esophageal carcinoma based on the number of metastatic lymph nodes is controversial. The present study analyzes prognostic implications of the number, extent, and size of metastatic lymph nodes for patients with esophageal squamous cell carcinoma (ESCC) treated with definitive (chemo-)radiotherapy to provide more information on treatment strategy. METHODS We reviewed 357 ESCC patients treated with definitive radiotherapy between January 2013 and March 2016 retrospectively. We assessed potential associations between the involved extent (N0, 1 region, 2 regions, and 3 regions), number (N0, 1-2, 3-6, and ≥ 7), and size (N0, ≤2 cm, and > 2 cm) of metastatic lymph nodes and overall survival. Multivariate analyses of the clinicopathological factors were performed using the Cox proportional hazard model. RESULTS 5-year survival rates were 43.6% for patients in the N0 group and 29.3% in the N+ group (p = 0.001). Kaplan-Meier analyses for all cases revealed that there were significant differences in survival based on the extent (the OS rates at 3 years were 53.3% for patients in the N0 group, 45.7% in the 1 region-involved group, 28.0% in the 2 regions-involved group, and 13.3% in the 3 regions-involved group, P < 0.001), number (the OS rates at 3 years were 49.0% for patients in the 1-2 LNs group, 27.8% in the 3-6 LNs group, 0 in the ≥7LNs group, P < 0.001), and size (the OS rates at 3 years were 41.6% for patients in the LNs ≤2 cm group and 20.7% in the LNs > 2 cm group, P = 0.001) of metastatic LNs. One hundred seventy-two patients (48.2%) had experienced GTV failure, 157 (43.1%) had distant failure, 49 (13.7%) had out-of-GTV nodal failure, and 70 patients (19.6%) had no evidence of disease at the last follow-up. Nodal status correlated statistically with GTV failure. Patients with LN metastases in the abdominal region had worse survival rates than those with metastases in the other regions. The extent and number of metastatic LNs, T category, Primary tumor location, and chemotherapy were independent prognostic factors of OS in multivariate analyses. CONCLUSIONS For patients with ESCC who received definitive (chemo-)radiotherapy, the number, extent, and size of metastatic LNs were prognostic factors, particularly of the T2/3 disease. Patients with LN metastases in the abdominal region had worse survival.
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Affiliation(s)
- Zongxing Zhao
- School of Medicine, Shandong University, Jinan, Shandong, China.,Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, China.,Department of Radiation Oncology, Liaocheng People's Hospital, Liaocheng, Shandong, China
| | - Yanan Zhang
- Department of Health Care, Liaocheng People's Hospital, Liaocheng, Shandong, China
| | - Peiliang Wang
- School of Medicine, Shandong University, Jinan, Shandong, China.,Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, China
| | - Xin Wang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, China.,Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Minghuan Li
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, China.
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Guo JC, Wu Y, Chen Y, Pan F, Wu ZY, Zhang JS, Wu JY, Xu XE, Zhao JM, Li EM, Zhao Y, Xu LY. Protein-coding genes combined with long noncoding RNA as a novel transcriptome molecular staging model to predict the survival of patients with esophageal squamous cell carcinoma. Cancer Commun (Lond) 2018; 38:4. [PMID: 29784063 PMCID: PMC5993132 DOI: 10.1186/s40880-018-0277-0] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Accepted: 12/18/2017] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal carcinoma in China. This study was to develop a staging model to predict outcomes of patients with ESCC. METHODS Using Cox regression analysis, principal component analysis (PCA), partitioning clustering, Kaplan-Meier analysis, receiver operating characteristic (ROC) curve analysis, and classification and regression tree (CART) analysis, we mined the Gene Expression Omnibus database to determine the expression profiles of genes in 179 patients with ESCC from GSE63624 and GSE63622 dataset. RESULTS Univariate cox regression analysis of the GSE63624 dataset revealed that 2404 protein-coding genes (PCGs) and 635 long non-coding RNAs (lncRNAs) were associated with the survival of patients with ESCC. PCA categorized these PCGs and lncRNAs into three principal components (PCs), which were used to cluster the patients into three groups. ROC analysis demonstrated that the predictive ability of PCG-lncRNA PCs when applied to new patients was better than that of the tumor-node-metastasis staging (area under ROC curve [AUC]: 0.69 vs. 0.65, P < 0.05). Accordingly, we constructed a molecular disaggregated model comprising one lncRNA and two PCGs, which we designated as the LSB staging model using CART analysis in the GSE63624 dataset. This LSB staging model classified the GSE63622 dataset of patients into three different groups, and its effectiveness was validated by analysis of another cohort of 105 patients. CONCLUSIONS The LSB staging model has clinical significance for the prognosis prediction of patients with ESCC and may serve as a three-gene staging microarray.
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Affiliation(s)
- Jin-Cheng Guo
- Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, Shantou, Guangdong 515041 P. R. China
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong 515041 P. R. China
| | - Yang Wu
- Key Laboratory of Intelligent Information Processing, Advanced Computer Research Center, State Key Laboratory of Computer Architecture, Institute of Computing Technology, Chinese Academy of Sciences, Beijing, 100190 P. R. China
| | - Yang Chen
- Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, Shantou, Guangdong 515041 P. R. China
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong 515041 P. R. China
| | - Feng Pan
- Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, Shantou, Guangdong 515041 P. R. China
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong 515041 P. R. China
| | - Zhi-Yong Wu
- Departments of Oncology Surgery, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-Sen University, Shantou, Guangdong 515041 P. R. China
| | - Jia-Sheng Zhang
- Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, Shantou, Guangdong 515041 P. R. China
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong 515041 P. R. China
| | - Jian-Yi Wu
- Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, Shantou, Guangdong 515041 P. R. China
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong 515041 P. R. China
| | - Xiu-E Xu
- Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, Shantou, Guangdong 515041 P. R. China
- Institute of Oncologic Pathology, Shantou University Medical College, Shantou, Guangdong 515041 P. R. China
| | - Jian-Mei Zhao
- Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, Shantou, Guangdong 515041 P. R. China
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong 515041 P. R. China
| | - En-Min Li
- Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, Shantou, Guangdong 515041 P. R. China
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong 515041 P. R. China
| | - Yi Zhao
- Key Laboratory of Intelligent Information Processing, Advanced Computer Research Center, State Key Laboratory of Computer Architecture, Institute of Computing Technology, Chinese Academy of Sciences, Beijing, 100190 P. R. China
| | - Li-Yan Xu
- Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, Shantou, Guangdong 515041 P. R. China
- Institute of Oncologic Pathology, Shantou University Medical College, Shantou, Guangdong 515041 P. R. China
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Prognostic Significant or Not? The Positive Circumferential Resection Margin in Esophageal Cancer. Ann Surg 2017; 266:988-994. [DOI: 10.1097/sla.0000000000001995] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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Metastatic to negative lymph node ratio demonstrates significant prognostic value in patients with esophageal squamous cell carcinoma after esophagectomy. Oncotarget 2017; 8:86908-86916. [PMID: 29156845 PMCID: PMC5689735 DOI: 10.18632/oncotarget.19673] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2017] [Accepted: 05/16/2017] [Indexed: 12/26/2022] Open
Abstract
Aims The prognostic value of metastatic lymph node ratio (LNR) has been reported in some studies; however, there is no report on the prognostic significance of metastatic to negative lymph node ratio (MNLNR) in cancer patients. The aim of this study was to compare the prognostic value of pN, LNR and MNLNR on the survival of patients with esophageal squamous cell carcinoma (ESCC) after esophagectomy. Methods The data of 290 patients with ESCC after curative esophagectomy was retrospectively analyzed. The optimal cut-point for LNR and MNLNR were set as 0, 01-0.2, and >0.2. Univariate and multivariate analyses were performed to identify prognostic factors for overall survival (OS). Results Patients classified as LNR 0, 0.01-0.20, and 0.21-1.0, the observed 5-year OS rates were 46.6%, 26.0%, and 11.6%, respectively (P = 0.000). Patients classified as MNLNR 0, 0.01-0.20, and >0.2, the observed 5-year OS rates were 46.6%, 31.2%, and 7.4%, respectively, respectively (P = 0.000). The pN stage, LNR or MNLNR category was confirmed as a significant independent prognostic factor, respectively (P = 0.032, P = 0.011 and P = 0.003, respectively); However, only the MNLNR category (P = 0.003) remained as a significant prognostic factor when the pN stage, LNR and MNLNR category simultaneously included in the multivariate analysis models. Conclusions The MNLNR was recognized as an independent prognostic factor in ESCC patients after curative esophagectomy. In addition, MNLNR showed better prognostic value than pN stage and LNR category.
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Numeric pathologic lymph node classification shows prognostic superiority to topographic pN classification in esophageal squamous cell carcinoma. Surgery 2017; 162:846-856. [PMID: 28739092 DOI: 10.1016/j.surg.2017.06.013] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Revised: 06/19/2017] [Accepted: 06/19/2017] [Indexed: 01/20/2023]
Abstract
BACKGROUND The current eighth tumor node metastasis lymph node category pathologic lymph node staging system for esophageal squamous cell carcinoma is based solely on the number of metastatic nodes and does not consider anatomic distribution. We aimed to assess the prognostic capability of the eighth tumor node metastasis pathologic lymph node staging system (numeric-based) compared with the 11th Japan Esophageal Society (topography-based) pathologic lymph node staging system in patients with esophageal squamous cell carcinoma. METHODS We retrospectively reviewed the clinical records of 289 patients with esophageal squamous cell carcinoma who underwent esophagectomy with extended lymph node dissection during the period from January 2006 through June 2016. We compared discrimination abilities for overall survival, recurrence-free survival, and cancer-specific survival between these 2 staging systems using C-statistics. RESULTS The median number of dissected and metastatic nodes was 61 (25% to 75% quartile range, 45 to 79) and 1 (25% to 75% quartile range, 0 to 3), respectively. The eighth tumor node metastasis pathologic lymph node staging system had a greater ability to accurately determine overall survival (C-statistics: tumor node metastasis classification, 0.69, 95% confidence interval, 0.62-0.76; Japan Esophageal Society classification; 0.65, 95% confidence interval, 0.58-0.71; P = .014) and cancer-specific survival (C-statistics: tumor node metastasis classification, 0.78, 95% confidence interval, 0.70-0.87; Japan Esophageal Society classification; 0.72, 95% confidence interval, 0.64-0.80; P = .018). Rates of total recurrence rose as the eighth tumor node metastasis pathologic lymph node stage increased, while stratification of patients according to the topography-based node classification system was not feasible. CONCLUSION Numeric nodal staging is an essential tool for stratifying the oncologic outcomes of patients with esophageal squamous cell carcinoma even in the cohort in which adequate numbers of lymph nodes were harvested.
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10
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Song G, Jing W, Xue S, Guo H, Yu J. The prognostic value of nodal skip metastasis in resectable thoracic esophageal squamous cell carcinoma. Onco Targets Ther 2017; 10:2729-2736. [PMID: 28579811 PMCID: PMC5449114 DOI: 10.2147/ott.s132062] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Purpose This study aimed to investigate the incidence of nodal skip metastasis (NSM) to identify the risk factors that influence NSM and to assess the prognostic value of NSM in patients with thoracic esophageal squamous cell carcinoma (ESCC). Patients and methods Between January 2009 and December 2013, 285 patients with ESCC with positive lymph nodes who underwent complete resection were enrolled. Results For the entire group, NSM occurred in 32.3% (92/285) of patients. The median survival time and 5-year survival rate in the NSM group were 28 months and 12.0%, respectively, compared with 36.3 months and 25.0%, respectively, in the non-NSM group (P=0.008). Both N stage (P=0.001) and T stage (P=0.014) were associated with the incidence of NSM. NSM (P=0.008), T stage (P=0.000), and N stage (P=0.000) were independent prognostic factors for survival. In the NSM group, T stage (P=0.014) and N stage (P=0.000) were independent prognostic factors for survival. Conclusion It was concluded that NSM is common in ESCC and is associated with poor survival.
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Affiliation(s)
- Ge Song
- Department of Radiation Oncology, School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences.,Department of Radiation Oncology, Shandong Cancer Hospital Affiliated with Shandong University, Jinan
| | - Wang Jing
- Department of Radiation Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou
| | - Song Xue
- Department of Radiation Oncology, School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences.,Department of Radiation Oncology, Shandong Cancer Hospital Affiliated with Shandong University, Jinan
| | - Hongbo Guo
- Department of Thoracic Surgery, Shandong Cancer Hospital Affiliated with Shandong University, Jinan, China
| | - Jinming Yu
- Department of Radiation Oncology, School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences.,Department of Radiation Oncology, Shandong Cancer Hospital Affiliated with Shandong University, Jinan
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11
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Chen SB, Weng HR, Wang G, Zou XF, Liu DT, Chen YP, Zhang H. Lymph node ratio-based staging system for esophageal squamous cell carcinoma. World J Gastroenterol 2015; 21:7514-7521. [PMID: 26139998 PMCID: PMC4481447 DOI: 10.3748/wjg.v21.i24.7514] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2014] [Revised: 01/06/2015] [Accepted: 03/19/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To analyze a modified staging system utilizing lymph node ratio (LNR) in patients with esophageal squamous cell carcinoma (ESCC).
METHODS: Clinical data of 2011 patients with ESCC who underwent surgical resection alone between January 1995 and June 2010 at the Cancer Hospital of Shantou University Medical College were reviewed. The LNR, or node ratio (Nr) was defined as the ratio of metastatic LNs ompared to the total number of resected LNs. Overall survival between groups was compared with the log-rank test. The cutoff point of LNR was established by grouping patients with 10% increment in Nr, and then combining the neighborhood survival curves using the log-rank test. A new TNrM staging system, was constructed by replacing the American Joint Committee on Cancer (AJCC) N categories with the Nr categories in the new TNM staging system. The time-dependent receiver operating characteristic curves were used to evaluate the predictive performance of the seventh edition AJCC staging system and the TNrM staging system.
RESULTS: The median number of resected LNs was 12 (range: 4-44), and 25% and 75% interquartile rangeswere8 and 16. Patients were classified into four Nr categories with distinctive survival differences (Nr0: LNR = 0; Nr1: 0% < LNR ≤ 10%; Nr2: 10% < LNR ≤ 20%; and Nr3: LNR > 20%). From N categories to Nr categories, 557 patients changed their LN stage. The median survival time (MST) for the four Nr categories (Nr0-Nr3) was 155.0 mo, 39.0 mo, 28.0 mo, and 19.0 mo, respectively, and the 5-year overall survival was 61.1%, 41.1%, 33.0%, and 22.9%, respectively (P < 0.001). Overall survival was significantly different for the AJCC N categories when patients were subgrouped into 15 or more vs fewer than 15 examined nodes, except for the N3 category (P = 0.292). However, overall survival was similar when the patients in all four Nr categories were subgrouped into 15 or more vs fewer than 15 nodes. Using the time-dependent receiver operating characteristic, we found that the Nr category and TNrM stage had higher accuracy in predicting survival than the AJCC N category and TNM stage.
CONCLUSION: A staging system based on LNR may have better prognostic stratification of patients with ESCC than the current TNM system, especially for those undergoing limited lymphadenectomy.
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Tan H, Zhang H, Xie J, Chen B, Wen C, Guo X, Zhao Q, Wu Z, Shen J, Wu J, Xu X, Li E, Xu L, Wang X. A novel staging model to classify oesophageal squamous cell carcinoma patients in China. Br J Cancer 2014; 110:2109-15. [PMID: 24569468 PMCID: PMC3992487 DOI: 10.1038/bjc.2014.101] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2013] [Revised: 01/03/2014] [Accepted: 01/29/2014] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Oesophageal squamous cell carcinoma (ESCC) is the predominant subtype of oesophageal carcinoma in China, with the overall 5-year survival rate of <10%. The current tumour-node-metastasis (TNM) staging system has become so complex that it is not easy to use in the life expectancy assessment. We aim to combine clinical variables and biomarkers to develop and validate a relative simple and reliable model, named the FENSAM, for ESCC prognosis. METHODS To build the FENSAM, we analysed 22 potential prognostic factors from 461 patients, including 9 biomarkers (Ezrin, Fascin, desmocollin 2 (DSC2), pFascin, activating transcription factor 3 (ATF3), connective-tissue growth factor (CTGF), neutrophil gelatinase-associated lipocalin (NGAL), NGAL receptor (NGALR), and cysteine-rich angiogenic protein 61 (CYR61)) and other 13 clinical variables. We selected significant factors associated with survival of ESCC patients, and used them to build our FENSAM model. We then obtained the hazard risk score of the model to classify ESCC patients. In addition, we validated the model in an independent cohort of 290 patients from the same hospital. The predictive performance of the model was assessed by the Area under the Receiver Operating Characteristic Curve (AUC) and Kaplan-Meier survival analysis. RESULTS We found six markers significantly associated with survival of ESCC patients (Ezrin, Fascin, ATF3, surgery extent, N-stage, and M-stage). They were combined to create a novel four-stage FENSAM model for patients' classification. FENSAM possessed a high classification precision similar to the TNM staging system, but with a much simpler model. The efficiency of FENSAM was evaluated by different quantiles of AUC and the results of survival analysis. The validation result demonstrated the potential of the FENSAM model to improve classification accuracy for ESCC patients. CONCLUSIONS FENSAM provides an alternative classifier for ESCC patients with a high classification precision using a simple model.
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Affiliation(s)
- H Tan
- Department of Biomedical Engineering, Zhongshan School of Medicine, Sun Yat-Sen University, 135 Xin Gang W. Road, Guangzhou, China
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, China
- Southern China Research Center of Statistical Science, Sun Yat-Sen University, Guangzhou 510275, China
| | - H Zhang
- Southern China Research Center of Statistical Science, Sun Yat-Sen University, Guangzhou 510275, China
- Yale University School of Public Health, New Haven, CT, USA
- Department of Statistical Science, School of Mathematics and Computational Science, Sun Yat-Sen University, Guangzhou, China
| | - J Xie
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, China
| | - B Chen
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, China
| | - C Wen
- Southern China Research Center of Statistical Science, Sun Yat-Sen University, Guangzhou 510275, China
- Department of Statistical Science, School of Mathematics and Computational Science, Sun Yat-Sen University, Guangzhou, China
| | - X Guo
- Southern China Research Center of Statistical Science, Sun Yat-Sen University, Guangzhou 510275, China
- Department of Statistical Science, School of Mathematics and Computational Science, Sun Yat-Sen University, Guangzhou, China
| | - Q Zhao
- Department of Pathology, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-Sen University, Shantou, China
| | - Z Wu
- Department of Pathology, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-Sen University, Shantou, China
| | - J Shen
- Department of Pathology, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-Sen University, Shantou, China
| | - J Wu
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, China
| | - X Xu
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, China
| | - E Li
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, China
| | - L Xu
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, China
| | - X Wang
- Department of Biomedical Engineering, Zhongshan School of Medicine, Sun Yat-Sen University, 135 Xin Gang W. Road, Guangzhou, China
- Southern China Research Center of Statistical Science, Sun Yat-Sen University, Guangzhou 510275, China
- Department of Statistical Science, School of Mathematics and Computational Science, Sun Yat-Sen University, Guangzhou, China
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The society of thoracic surgeons guidelines on the diagnosis and staging of patients with esophageal cancer. Ann Thorac Surg 2013; 96:346-56. [PMID: 23752201 DOI: 10.1016/j.athoracsur.2013.02.069] [Citation(s) in RCA: 67] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2012] [Revised: 02/15/2013] [Accepted: 02/25/2013] [Indexed: 12/17/2022]
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Chen SB, Weng HR, Wang G, Yang JS, Yang WP, Liu DT, Chen YP, Zhang H. Prognostic factors and outcome for patients with esophageal squamous cell carcinoma underwent surgical resection alone: evaluation of the seventh edition of the American Joint Committee on Cancer staging system for esophageal squamous cell carcinoma. J Thorac Oncol 2013; 8:495-501. [PMID: 23446203 DOI: 10.1097/jto.0b013e3182829e2c] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
INTRODUCTION More data are essential to test the efficacy of the seventh edition of the American Joint Committee on Cancer (AJCC) staging system for esophageal squamous cell carcinoma (ESCC). This retrospective study was designed to identify the prognostic factors for survival of patients with ESCC who underwent surgical resection alone and to evaluate the new AJCC staging system for ESCC. METHODS Data of a single-center cohort of 2011 patients with ESCC who underwent surgical resection alone according to the new staging system were reviewed. Univariate and multivariate analyses were performed to identify prognostic factors. RESULTS The 1-, 3-, and 5-year overall survival rates were 83.5, 57.4, and 47.4%, respectively, with a median survival time of 51.0 months. Age, histologic grade, R-category, pT category, pN category, pM category, pTNM stage, and the extent of lymph node metastasis were independent prognostic factors (p < 0.05). In separate subgroup analyses, the survival differences were not significant for pN2 versus pN3 category (p = 0.159) and stages IA versus IB (p = 0.922). Subdivisions by depth of infiltration rather than tumor grade for pT1N0M0 cancers and modified nodal categories (0, 1, 2-3, and ≥4 positive lymph nodes) better represented a survival advantage. CONCLUSIONS The seventh edition of the AJCC staging system for ESCC is acceptable in predicting survival. However, tumor location does not influence survival in our study. Subdivisions of pT1N0M0 cancers and the N-classification may need to be modified.
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Affiliation(s)
- Shao-Bin Chen
- Department of Thoracic Surgery, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China
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Hou X, Wei JC, Xu Y, Luo RZ, Fu JH, Zhang LJ, Lin P, Yang HX. The positive lymph node ratio predicts long-term survival in patients with operable thoracic esophageal squamous cell carcinoma in China. Ann Surg Oncol 2012; 20:1653-9. [PMID: 23247981 DOI: 10.1245/s10434-012-2794-4] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2012] [Indexed: 12/12/2022]
Abstract
BACKGROUND Controversy exists concerning the optimal cutoff points for the positive lymph node ratio (PLNR) to predict overall survival. We aim to propose reasonable PLNR categories for the discrimination of the survival difference between groups. METHODS We used data from two centers to establish a training (n = 1006) and a validation (n = 783) cohort. All of the patients underwent curative surgical treatment. Martingale residuals from a Cox proportional hazards regression model were used to determine the optimal cutoff points for PLNR to predict overall survival. The survival rate was calculated using the Kaplan-Meier method, and a log-rank test was used to assess the survival differences between groups. The results obtained from the training cohort were tested with the validation cohort at each step. RESULTS We classified the patients into four revised nodal categories: R-pN0 (PLNR = 0), R-pN1 (0< PLNR ≤0.1), R-pN2 (0.1< PLNR ≤0.3), and R-pN3 (PLNR >0.3). Subgroup analysis for the pT2 and pT3 cases showed that the survival differences could be well discriminated between groups based on PLNR in both the training cohort and validation cohort. When we modified the current staging system using revised nodal categories (based on PLNR) instead of the AJCC nodal categories, the survival rate could also be easily distinguished between patients in different stages in both cohorts of patients. CONCLUSIONS The survival rate of ESCC can be discriminated between four groups: PLNR = 0, 0< PLNR ≤0.1, 0.1< PLNR ≤0.3, and PLNR >0.3. Further studies are required to confirm these results.
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Affiliation(s)
- Xue Hou
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China
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TAKENO SHINSUKE, YAMASHITA SHINICHI, YAMAMOTO SATOSHI, TAKAHASHI YOSHIAKI, MOROGA TOSHIHIKO, KAWAHARA KATSUNOBU, SHIROSHITA TOYOO, YAMANA IPPEI, MAKI KENJI, YAMASHITA YUICHI. Number of metastasis-positive lymph node stations is a simple and reliable prognostic factor following surgery in patients with esophageal cancer. Exp Ther Med 2012; 4:1087-1091. [PMID: 23226779 PMCID: PMC3494111 DOI: 10.3892/etm.2012.705] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2012] [Accepted: 07/27/2012] [Indexed: 12/31/2022] Open
Abstract
The aim of this study was to evaluate the utility of lymph node metastasis classification based on the number of positive stations in patients undergoing surgical management of esophageal cancer. Of 257 patients who underwent curative esophagectomy, 126 patients with lymph node involvement underwent assessment of nodal metastasis mode according to the 7th edition of the TNM classification (UICC), and the Japanese Guidelines for the Clinical and Pathological Studies on Carcinoma of the Esophagus. Lymph node metastasis mode was divided into single station (S) and multi-station (M) groups. The S group was subclassified into single-node-single-station (SS) or multi-node-single-station (MS), and the M group was subclassified into multi-station in pN1 (2 metastasis positive nodes; MM-pN1) or multi-station in pN2 or 3 (MM-pN2,3) by TNM classification, multi-station-single-area (MMS) or multi-station-multi-areas (MMM). The correlation between prognosis and lymph node metastasis mode was assessed. A total of 47 patients were classified as S (MS, n=11; SS, n=36), and 79 patients were classified as M (MM-pN1, n=12; MM-pN2,3, n=67; MMM, n=55; MMS, n=24). Prognosis was poorer among the M- than in the S-classified patients (p=0.0035), whereas prognosis was not significantly different between the subgroups. In conclusion, lymph node metastasis classification based on the number of metastasis-positive stations is a useful predictor of prognosis in patients undergoing surgical management of esophageal cancer. This system relies on a simple classification method that combines the Japanese classification based on lymphatic spread and the TNM classification based on the number of positive lymph nodes.
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Affiliation(s)
- SHINSUKE TAKENO
- Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka City, Fukuoka
- Department of Surgery II, Oita University Faculty of Medicine, Oita,
Japan
| | | | - SATOSHI YAMAMOTO
- Department of Surgery II, Oita University Faculty of Medicine, Oita,
Japan
| | - YOSHIAKI TAKAHASHI
- Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka City, Fukuoka
| | - TOSHIHIKO MOROGA
- Department of Surgery II, Oita University Faculty of Medicine, Oita,
Japan
| | - KATSUNOBU KAWAHARA
- Department of Surgery II, Oita University Faculty of Medicine, Oita,
Japan
| | - TOYOO SHIROSHITA
- Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka City, Fukuoka
| | - IPPEI YAMANA
- Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka City, Fukuoka
| | - KENJI MAKI
- Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka City, Fukuoka
| | - YUICHI YAMASHITA
- Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka City, Fukuoka
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Zhang HQ, Wang RB, Yan HJ, Zhao W, Zhu KL, Jiang SM, Hu XG, Yu JM. Prognostic significance of CYFRA21-1, CEA and hemoglobin in patients with esophageal squamous cancer undergoing concurrent chemoradiotherapy. Asian Pac J Cancer Prev 2012; 13:199-203. [PMID: 22502668 DOI: 10.7314/apjcp.2012.13.1.199] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
PURPOSE To evaluate the prognostic value of serum CYFRA21-1, CEA and hemoglobin levels regarding long-term survival of patients with esophageal squamous cell carcinoma (ESCC) treated with concurrent chemoradiotherapy (CRT). METHODS Age, gender, Karnofsky Performance Status (KPS), tumor location, tumor length, T stage, N stage and serum hemoglobin, and CYFRA21-1 and CEA levels before concurrent CRT were retrospectively investigated and related to outcome in 113 patients receiving 5-fluorouracil and cisplatin combined with radiotherapy for ESCC. The Kaplan-Meier method was used to analyze prognosis, the log-rank to compare groups, the Cox proportional hazards model for multivariate analysis, and ROC curve analysis for assessment of predictive performance of biologic markers. RESULTS The median survival time was 20.1 months and the 1-, 2-, 3-, 5- year overall survival rates were 66.4%, 43.4%, 31.9% and 15.0%, respectively. Univariate analysis showed that factors associated with prognosis were KPS, tumor length, T-stage, N-stage, hemoglobin, CYFRA21-1 and CEA level. Multivariate analysis showed T-stage, N-stage, hemoglobin, CYFRA21-1 and CEA level were independent predictors of prognosis. By ROC curve, CYFRA21-1 and hemoglobin showed better predictive performance for OS than CEA (AUC= 0.791, 0.704, 0.545; P=0.000, 0.000, 0.409). CONCLUSIONS Of all clinicopathological and molecular factors, T stage, N stage, hemoglobin, CYFRA21-1 and CEA level were independent predictors of prognosis for patients with ESCC treated with concurrent CRT. Among biomarkers, CYFRA21-1 and hemoglobin may have a better predictive potential than CEA for long-term outcomes.
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Affiliation(s)
- Hai-Qin Zhang
- Department of Radiation Oncology, Shandong Cancer Hospital, Jinan, China
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Reeh M, Nentwich MF, von Loga K, Schade J, Uzunoglu FG, Koenig AM, Bockhorn M, Rosch T, Izbicki JR, Bogoevski D. An attempt at validation of the Seventh edition of the classification by the International Union Against Cancer for esophageal carcinoma. Ann Thorac Surg 2012; 93:890-6. [PMID: 22289905 DOI: 10.1016/j.athoracsur.2011.11.035] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2011] [Revised: 11/13/2011] [Accepted: 11/14/2011] [Indexed: 11/28/2022]
Abstract
BACKGROUND The aim of our study was to investigate the ability of the Seventh edition of the classification by the International Union Against Cancer (UICC) to identify patients at higher risk and to predict the overall survival in patients with esophageal carcinoma. METHODS Demographic and clinical data of 605 patients, who underwent esophagectomy for esophageal carcinoma between 1992 and 2009, were analyzed. Tumor stage and grade were classified according to the sixth and seventh editions of the UICC classification. RESULTS Tumor depth (T), lymph node affection (N), and metastasis (M) status according to the seventh edition of the UICC classification showed significant differences in survival of each single status. Kaplan-Meier analysis of overall survival by the seventh edition of the UICC classification showed poor discrimination between stages Ib and IIa (p=0.098), stages IIIa and IIIb (p=0.672), and stages IIIc and IV (p=0.799). Further, the estimated median survival time between stages IIa and IIb was discordant. CONCLUSIONS The seventh edition of the UICC TNM classification cannot satisfactorily distinguish among different risk groups of patients with resected esophageal carcinoma. The new subgroups do not unify the different TNM stages with similar survival. We strongly propose that the next revision of the UICC classification should reduce the stages to groups with similar survival, without defining complex subgroups.
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Affiliation(s)
- Matthias Reeh
- Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
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de Manzoni G, Steccanella F, Zanoni A. Classification and Staging Systems. Updates Surg 2012. [DOI: 10.1007/978-88-470-2330-7_2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
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Kayani B, Zacharakis E, Ahmed K, Hanna GB. Lymph node metastases and prognosis in oesophageal carcinoma--a systematic review. Eur J Surg Oncol 2011; 37:747-53. [PMID: 21839394 DOI: 10.1016/j.ejso.2011.06.018] [Citation(s) in RCA: 67] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2010] [Revised: 02/09/2011] [Accepted: 06/28/2011] [Indexed: 12/27/2022] Open
Abstract
Oesophageal cancer is the 7th most common cause of cancer-related death in the developed world and the incidence of oesophageal adenocarcinoma is now the fastest growing of any gastrointestinal cancer. Lymph node involvement is the single most important prognostic factor in oesophageal cancer. Imaging to determine the extent of lymph node involvement and plan treatment often requires a combination of modalities to avoid under-staging. The 7th edition of the staging system released by the International Union Against Cancer (IUCC) has stratified lymph node involvement according to the number of lymph nodes involved and redefined its groupings for location of metastatic lymph node involvement. This review discusses the prognostic and treatment implications of these modifications and explores micrometastatic lymph node involvement, capsular infiltration and lymph node ratio as possible additions to the staging system.
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Affiliation(s)
- B Kayani
- Department of Surgery and Cancer, Imperial College London, St Mary's Hospital, Praed Street, London W2 1NY, UK
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The N-classification for esophageal cancer staging: should it be based on number, distance, or extent of the lymph node metastasis? World J Surg 2011; 35:1303-10. [PMID: 21452071 DOI: 10.1007/s00268-011-1015-9] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND The recently published AJCC-TNM staging system for esophageal carcinoma made an obvious modification on N-classification based on the number of metastatic regional lymph nodes (LN). However, this classification might ignore the site at which these LNs occur, a factor that might be even more important in reflecting patients' prognosis. METHODS A retrospective study of 236 patients with carcinoma of thoracic esophagus who underwent esophagectomy between 1984 and 1989 with each at least six LNs removed was conducted, with a 10-year follow-up rate of 92.4%. The proposed scheme for N-classification according to the number (0, 1-2, 3-6, ≥7; N0-3), distance (0, 1, 2, 3 stations; S0-3), or extent (0, 1, and 2 fields; F0-2) of LN involvement was evaluated by univariate and multivariate survival analysis. RESULTS The LN metastasis was identified in 112 patients, revealing a poorer 5-year survival in this patient group when compared to patients without node involvement. Cox regression analysis revealed that the number and distance of LN metastases and the number of metastasis fields were factors significantly influencing survival. When these factors were further analyzed by univariate log-rank test, no significant difference in survival existed between N2 and N3 patients, or among S1, S2, and S3 patients. When patients were grouped according to the extent of LN metastasis, significant differences in survival were observed overall and between each subgroup. CONCLUSIONS Refining the current N-classification for esophageal cancer according to the extent of LN metastasis, rather than by number alone, might be a better means of staging that could subgroup patients more effectively and result in different rates of survival.
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Kunisaki C. Reply to a letter to the editor for “Impact of site of lymph node metastasis in patients with thoracic esophageal cancer”. J Surg Oncol 2011. [DOI: 10.1002/jso.21705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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Modification of Nodal Categories in the Seventh American Joint Committee on Cancer Staging System for Esophageal Squamous Cell Carcinoma in Chinese Patients. Ann Thorac Surg 2011; 92:216-24. [DOI: 10.1016/j.athoracsur.2011.03.032] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2011] [Revised: 03/07/2011] [Accepted: 03/09/2011] [Indexed: 01/02/2023]
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Gaur P, Hofstetter WL, Bekele BN, Correa AM, Mehran RJ, Rice DC, Roth JA, Vaporciyan AA, Rice TW, Swisher SG. Comparison Between Established and the Worldwide Esophageal Cancer Collaboration Staging Systems. Ann Thorac Surg 2010; 89:1797-1803, 1804.e1-3; discussion 1803-4. [DOI: 10.1016/j.athoracsur.2010.02.048] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2009] [Revised: 02/11/2010] [Accepted: 02/12/2010] [Indexed: 11/28/2022]
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Yang HX, Xu Y, Fu JH, Wang JY, Lin P, Rong TH. An evaluation of the number of lymph nodes examined and survival for node-negative esophageal carcinoma: data from China. Ann Surg Oncol 2010; 17:1901-11. [PMID: 20146101 DOI: 10.1245/s10434-010-0948-9] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2009] [Indexed: 01/15/2023]
Abstract
BACKGROUND The current American Joint Committee on Cancer (AJCC) staging system for esophageal cancer does not define the minimum number of lymph nodes (LNs) necessary for accurate nodal staging. This study aimed to seek the minimum number of LNs examined for adequate nodal staging of patients with node-negative esophageal cancer. METHODS We conducted a retrospective review of 592 patients undergoing R0 resection with node-negative esophageal carcinoma between December 1996 and December 2004. The relationship between the total number of examined LNs and death from esophageal cancer was investigated by means of a scatterplot of this variable versus Martingale residuals from a Cox proportional hazard regression model without the variable of interest. A smoothed line fit of the scatterplot was applied to detect the reasonable cutoff point. RESULTS The patients were classified into four categories according to the number of examined LNs: < or =5, 6 to 9, 10 to 17, and > or =18. A reduced hazard ratio of death was observed with an increasing number of LNs examined. The 5-year cancer-specific survival rate was 42.8% among patients with < or =5 LNs examined, compared with 52.6, 56.8, and 75% for those with 6-9 LNs, 10-17 LNs, and > or =18 LNs, respectively. Multivariate Cox regression analysis suggested that female sex, lower grade of cell differentiation, lower T category and increasing number of examined LNs were independent factors favoring cancer-specific survival. CONCLUSIONS At least 18 LNs should be resected for accurate staging of operable esophageal carcinoma. However, a validation from other institute is warranted.
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Affiliation(s)
- Hao-Xian Yang
- Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
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Kunisaki C, Makino H, Kimura J, Oshima T, Fujii S, Takagawa R, Kosaka T, Ono HA, Akiyama H. Impact of lymph-node metastasis site in patients with thoracic esophageal cancer. J Surg Oncol 2010; 101:36-42. [PMID: 19921710 DOI: 10.1002/jso.21425] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND AND OBJECTIVES We retrospectively compared surgical outcomes between patients with intra-thoracic and extra-thoracic (cervical and abdominal) lymph-node metastasis. METHODS The study population comprised 96 patients with lymph-node metastasis who had undergone curative esophagectomy for thoracic esophageal cancer. The patients were grouped according to whether the site of lymph-node metastasis was intra-thoracic, extra-thoracic, or both intra-thoracic and extra-thoracic. The patient characteristics, survival time, and prognostic factors were compared. RESULTS The most significant difference in disease-specific survival was detected at a threshold value of four metastatic lymph nodes. Lymph-node metastasis was observed at intra-thoracic sites in 41 patients, at extra-thoracic sites in 20 patients, and at both intra-thoracic and extra-thoracic sites in 35 patients. Intra-thoracic lymph-node metastasis was frequently observed in patients with middle and upper thoracic esophageal cancer. There was no difference in the number of metastatic lymph nodes between patients with intra-thoracic and extra-thoracic lymph-node metastasis. Multivariate analysis revealed that the number of metastatic lymph nodes was an independent prognostic factor, whereas the site of metastatic lymph nodes was not. CONCLUSIONS These findings suggest that the surgical outcomes in patients with thoracic esophageal cancer depend on the number, but not the site, of metastatic lymph nodes after curative esophagectomy.
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Affiliation(s)
- Chikara Kunisaki
- Department of Surgery, Gastroenterological Center, Yokohama City University, 4-57 Urafune-cho, Minami-ku, Yokohama 232-0024, Japan.
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Zhang HL, Chen LQ, Liu RL, Shi YT, He M, Meng XL, Bai SX, Ping YM. The number of lymph node metastases influences survival and International Union Against Cancer tumor-node-metastasis classification for esophageal squamous cell carcinoma. Dis Esophagus 2010; 23:53-8. [PMID: 19392846 DOI: 10.1111/j.1442-2050.2009.00971.x] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
To study the influence of the number of metastatic lymph nodes (LNs) on survival and International Union Against Cancer tumor-node-metastasis (TNM) classification for esophageal carcinoma. The clinicopathological data on 1146 patients with esophageal squamous cell carcinoma who had undergone an esophagectomy were retrospectively studied. Survival was analyzed by the Kaplan-Meier method. By subclassifying the nodes (N) category according to the number of metastatic LNs as: N0 for no LN metastases; N1(1) for only one positive node; and N1(2) for >or=2 positive nodes. TNM staging was refined as stage IIa (T2-3N0M0), stage IIb (T1N1M0 and T2N1(1)M0), stage IIIa (T2N1(2)M0 and T3N1(1)M0), and stage IIIb (T3N1(2)M0 and T4NanyM0), and the survival was analyzed. LN metastases was found in 380 of 1146 (33.2%) treated esophageal cancer patients. In 4270 LNs harvested, metastases was detected in 807 (18.9%). The 5-year survival rates of the patients with 0, 1, and >or=2 positive nodes were 59.8, 33.4, and 9.4%, respectively. There was statistically significant difference among these three groups. The 5-year survival of the patients in stages T2N1M0 and T3N1M0 was significantly higher in the N1(1) group than in the N1(2) group (41.5 vs 24.1%, and 31.2 vs 6.8%, P<0.001). The 5-year survival rates of the patients in refined stage IIa, IIb, IIIa, and IIIb were 57.1, 42.2, 28.6, and 8.5%, with significant difference existing in each stage groups. The number of positive LNs significantly influenced survival of the patients with esophageal cancer. Three grade classification (0, 1, >or=2 positive nodes) could quite well demonstrate the effect of the number of LN metastases and the survival. The refined TNM classification based on the number of LN metastases could better reflect the prognosis of esophageal cancer. Our results offer a strong rationale for refining the International Union Against Cancer TNM classification for esophageal carcinoma.
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Affiliation(s)
- H-L Zhang
- Department of Thoracic Surgery, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
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Hu Y, Hu C, Zhang H, Ping Y, Chen LQ. How does the number of resected lymph nodes influence TNM staging and prognosis for esophageal carcinoma? Ann Surg Oncol 2009; 17:784-90. [PMID: 19953333 DOI: 10.1245/s10434-009-0818-5] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2009] [Indexed: 02/05/2023]
Abstract
BACKGROUND It is proposed by International Union Against Cancer (UICC) and American Joint Committee on Cancer (AJCC) that at least 6 lymph nodes (LN) should be removed during resection of esophageal cancer for an accurate N classification. However, large series evidence is needed. The aim of this study is to assess the impact of total number of removed LNs during esophagectomy on UICC-TNM staging and long-term survival. MATERIALS AND METHODS The clinicopathological data and follow-up results of 1098 patients with advanced esophageal carcinoma who underwent an esophagectomy were analyzed. RESULTS The survival experience of group A (removed LNs <6) was worse than that of group B (removed LNs > or = 6). With the stratification analysis according to N and TNM stage, for patients with pN0 cancers, the survival in group A was worse than that in group B (P = .003), while in patients with 1 and > or = 2 positive LNs, the survival experience was similar (P = .919 and .182, respectively). A significant difference in survival in patients at stage IIa was observed between group A and group B (P = .005). However, the survival in patients at stage IIb and stage III was not different between the two groups (P = .302 and 0.108, respectively). CONCLUSIONS For advanced esophageal carcinoma, if the number of resected LNs per operation is less than 6, an occult positive regional LN might be missed, resulting in an inaccurate N classification. The minimum of 6 LNs removed for esophageal cancer recommended by UICC and AJCC is rational and should be complied with.
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Affiliation(s)
- Yang Hu
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
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Twine CP, Lewis WG, Morgan MA, Chan D, Clark GWB, Havard T, Crosby TD, Roberts SA, Williams GT. The assessment of prognosis of surgically resected oesophageal cancer is dependent on the number of lymph nodes examined pathologically. Histopathology 2009; 55:46-52. [PMID: 19614766 DOI: 10.1111/j.1365-2559.2009.03332.x] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
AIMS The prognosis in surgically resected oesophageal carcinoma (OC) is dependent on the number of regional lymph nodes (LN) involved, but no guidance exists on how many LNs should be examined histopathologically to give a reliable pN status. The aim of this study was to determine whether the number of LNs examined after OC resection has a significant effect on the assessment of prognosis. METHODS AND RESULTS Routinely generated pathology reports from 237 consecutive patients undergoing oesophagectomy for OC were examined and analysed in relation to survival. The main outcome measure was survival from date of diagnosis. Lymph node count (LNC) correlated strongly with survival; a plateau was reached after a count of 10. Median and 2-year survival was 30 months and 42%, respectively, if <10 nodes were examined (n = 88), compared with 51 months and 61% if >10 nodes were examined (P = 0.005). This effect was greatest in pN0 cases. The prognostic value of the absolute number of LN metastases (<4) and LN ratio (<0.4) was strongly dependent on a LNC of >10. CONCLUSIONS These results demonstrate the importance of careful pathological examination and lymph node retrieval after OC resection. At least 10 nodes should be examined to designate an OC as pN0.
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Affiliation(s)
- Christopher P Twine
- South East Wales Cancer Network, Department of General and Upper GI Surgery, University Hospital of Wales, Cardiff Cardiff, UK
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Kalaitzakis E, Meenan J. Controversies in the use of endoscopic ultrasound in esophageal cancer staging. Scand J Gastroenterol 2009; 44:133-44. [PMID: 18654933 DOI: 10.1080/00365520802273066] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- Evangelos Kalaitzakis
- Department of Gastroenterology, St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.
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Thompson SK, Ruszkiewicz AR, Jamieson GG, Esterman A, Watson DI, Wijnhoven BPL, Lamb PJ, Devitt PG. Improving the accuracy of TNM staging in esophageal cancer: a pathological review of resected specimens. Ann Surg Oncol 2008; 15:3447-3458. [PMID: 18830669 DOI: 10.1245/s10434-008-0155-0] [Citation(s) in RCA: 62] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2008] [Revised: 08/14/2008] [Accepted: 08/14/2008] [Indexed: 02/11/2025]
Abstract
BACKGROUND Controversy exists over the Sixth Edition of the International Union Against Cancer (UICC) TNM staging system for esophageal cancer. Inclusion of additional information such as the number of metastatic lymph nodes and extracapsular lymph node invasion may improve the current staging system and lead to optimization of patient treatment. METHODS All patients in Adelaide who underwent resection for esophageal cancer between 1997 and 2007 were identified from a prospective database. Two independent observers then reexamined all pathology slides from the original resection. Univariate and multivariate analysis was performed to identify significant prognostic factors. The goodness of fit and accuracy of additional prognostic factors were assessed, and the staging system was modified according to this information. RESULTS There were 240 patients (mean age, 62 years) who met the inclusion criteria. The 5-year overall survival rate was 36% (median, 24 months). Only histological grade and a refined pN stage were found to be independent prognostic factors that could then be used to improve current TNM staging. Subdivision of pN stage into three groups (0, 1-2, and >2 positive nodes) showed significant differences in 5-year survival between all three groups: 53% vs 27% vs 6%, respectively (P < .01). The optimal staging model was the same for patients who received neoadjuvant therapy and surgery (n = 116), and those who underwent surgery alone (n = 124). CONCLUSION A staging model that incorporates a refined pN stage and histological grade appears to be more accurate than the current UICC-TNM staging system. This staging model is still applicable in patients who receive neoadjuvant therapy.
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Affiliation(s)
- Sarah K Thompson
- Discipline of Surgery, University of Adelaide, Adelaide, South Australia, Australia.
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Abstract
PURPOSE To investigate the importance of lymph node yield (LNY) and the ratio of afflicted lymph nodes in esophageal carcinoma patients. PATIENTS AND METHODS Between 1992 and 2004, 368 patients with esophageal carcinoma underwent surgery. Esophagectomy with curative intent was performed in 255 patients. Subtotal esophagectomy was performed either by thoracoabdominal (104 patients, 40.8%) or by transhiatal approach (151 patients, 59.2%). RESULTS According to the LNY, patients were grouped into 3 groups. Twenty-six patients had < or =5, 96 had 6 to 18, and 113 had > or =19 dissected lymph nodes. In patients with nodal involvement (pN1), no significant overall survival differences were identified when stratifying subgroups according to the LNY. However, LNY had striking prognostic relevance in pN0 patients. The median overall survival was 23 (< or =5 LN), 36 (6-18 LN), and 88 months (> or =19). Even for patients with tripled LNY than the proposed minimum by the International Union Against Cancer (UICC) (18 LN), the rate of patients with detected lymph node metastases was only 46%, compared with 61% for patients with a LNY of > or =19 (P = 0.002). In pN1 patients classified according to the ratio of afflicted lymph nodes, median overall survival was 27 months in patients with a ratio <11%, compared with 15 and 13 months in patients with a ratio of 11% to 33% and >33%, respectively (P < 0.001). Multivariate Cox regression modeling identified ratio as the strongest independent prognostic factor for overall survival in pN1 and the LNY in pN0 patients. CONCLUSIONS The minimal regional LNY of 6 lymph nodes as recommended by the UICC for esophageal carcinoma is far too low to appropriately stage the disease. The LNY and the ratio should be reflected in the next version of the UICC classification.
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Prognostic significance of the number of lymph node metastases in esophageal cancer. J Am Coll Surg 2007; 206:239-46. [PMID: 18222375 DOI: 10.1016/j.jamcollsurg.2007.09.003] [Citation(s) in RCA: 88] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2007] [Revised: 08/20/2007] [Accepted: 09/05/2007] [Indexed: 12/26/2022]
Abstract
BACKGROUND Regional lymph node (LN) involvement is one of the most important predictors of survival for patients with esophageal cancer. The current staging classification differentiates only between the presence and absence of LN metastasis. In this study, we examined whether involvement of a higher number of LNs is associated with worse survival among esophageal cancer patients. STUDY DESIGN We identified all patients who underwent operations for node-positive esophageal cancer between 1988 and 2003 from the Surveillance, Epidemiology and End Results cancer registry. Because the number of positive LNs is confounded by the total number of LNs removed, patients were classified into three groups by the ratio of positive-to-total number of LNs removed (LN ratio [LNR]): <or= 0.2, 0.21 to 0.5, and>0.5. Esophageal cancer-specific survival was compared among these groups using Kaplan-Meier curves. Stratified and Cox regression analyses were used to evaluate the relationship between the LNR and survival after adjusting for potential confounders. RESULTS The study cohort included 838 esophageal cancer patients. Disease-specific survival rates decreased with higher LNR. Five-year disease-specific survival was 30% among patients with an LNR<or=0.2, compared with 16% and 13% for those with LNs of 0.21 to 0.5 and>0.5, respectively (p < 0.001). In stratified and multivariable analyses controlling for age, race, gender, histology, tumor-status, and postoperative radiotherapy, a higher LNR was independently associated with worse disease-specific survival. CONCLUSIONS These data suggest that a higher LNR among patients with node-positive esophageal cancer is associated with worse survival. If validated, this prognostic criterion may be included in staging classifications.
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Hofstetter W, Correa AM, Bekele N, Ajani JA, Phan A, Komaki RR, Liao Z, Maru D, Wu TT, Mehran RJ, Rice DC, Roth JA, Vaporciyan AA, Walsh GL, Francis A, Blackmon S, Swisher SG. Proposed modification of nodal status in AJCC esophageal cancer staging system. Ann Thorac Surg 2007; 84:365-73; discussion 374-5. [PMID: 17643602 DOI: 10.1016/j.athoracsur.2007.01.067] [Citation(s) in RCA: 81] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2006] [Revised: 01/24/2007] [Accepted: 01/29/2007] [Indexed: 11/18/2022]
Abstract
BACKGROUND The current American Joint Committee on Cancer (AJCC) esophageal cancer staging for nodal status is difficult to interpret and is based solely on lymph node location relative to the primary tumor's esophageal location. Recent reports suggest that the number of lymph nodes involved is also an important factor. We reviewed our esophageal experience to propose an improved nodal staging system. METHODS In all, 1,027 patients with resected esophageal cancer from 1970 to 2005 were reviewed. Lymph nodes stations were assigned according to AJCC criteria. Overall survival was assessed by Kaplan-Meier analysis. The impact of location, number of involved lymph nodes, and use of preoperative chemotherapy or radiation therapy, or both, was assessed. RESULTS Nonregional nodal involvement (n = 17) was associated with decreased survival compared with regional (n = 441) or celiac nodal (n = 73) involvement (3-year: 0% versus 24% and 23%; p < 0.001). The number of involved lymph nodes was strongly associated with survival (3-year: 0 nodes = 63%, 1 to 3 nodes = 31%, more than 3 nodes = 13%; p < 0.001), and multivariable Cox proportional-hazards analysis suggested that the location and number of involved lymph nodes were independent predictors of survival (p < 0.001). We propose a modified nodal staging system that designates celiac nodes as regional and includes number of involved nodes: pN0, no nodes (3 years = 63%, n = 496); pN1-regional, 1 to 3 nodes (3 years = 32%, n = 292); pN2-regional, more than 3 nodes (3 years = 14%, n = 222); pN3-nonregional node (3 years = 0%, n = 17 [p < 0.0001]). This modified nodal staging system better predicts survival than the current AJCC nodal staging system in which survival for pN1 (3 years = 24%) and pM1a (3 years = 23%) do not differ (p = 0.67). The use of induction before surgical resection did not alter the predictive effect of the new nodal staging system. CONCLUSIONS Modification of the AJCC nodal classification system to incorporate the number of involved lymph nodes with regional and nonregional node location simplifies and better predicts long-term survival than does the current AJCC nodal system.
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Affiliation(s)
- Wayne Hofstetter
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
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Abstract
Cancer of the esophagus continues to be a threat to public health. The common practice is esophagectomy for surgically resectable tumors and radiochemotherapy for locally advanced, unresectable tumors. However, local regional tumor control and overall survival of esophageal cancer patients after the standard therapies remain poor, approximately 30% of patients treated with surgery only will develop local recurrence, and 50% to 60% patients treated with radiochemotherapy only fail local regionally due to persistent disease or local recurrence. Esophagectomy after radiochemotherapy or preoperative radiochemotherapy has increased the complete surgical resection rate and local regional control without a significant survival benefit. Induction chemotherapy followed by preoperative radiochemotherapy has produced encouraging results. In addition to patient-, tumor-, and treatment-related factors, involvement of celiac axis nodes, number of positive lymph nodes after preoperative radiochemotherapy, incomplete pathologic response, high metabolic activity on positron emission tomography scan after radiochemotherapy, and incomplete surgical resection are factors associated with a poor outcome. Radiochemotherapy followed by surgery is associated with significant adverse effects, including treatment-related pneumonitis, postoperative pulmonary complications, esophagitis and pericarditis. The incidence and severity of the adverse effects are associated with chemotherapy and radiotherapy dosimetric factors. Innovative treatment strategies including physically and biologically molecular targeted therapy is needed to improve the treatment outcome of patients with esophageal cancer.
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Affiliation(s)
- Zhongxing Liao
- Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer, Houston, Texas 77030, USA.
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Kaiser S. Commentary on “surgical outcome after the clearance of abdominal metastatic lymph nodes in 138 patients with thoracic esophageal carcinoma”. Am J Surg 2007. [DOI: 10.1016/j.amjsurg.2006.08.079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Oñate-Ocaña LF, Milán-Revollo G, Aiello-Crocifoglio V, Carrillo JF, Gallardo-Rincón D, Brom-Valladares R, Herrera-Goepfert R, Dueñas-González A. Treatment of the Adenocarcinoma of the Esophagogastric Junction at a Single Institution in Mexico. Ann Surg Oncol 2007; 14:1439-48. [PMID: 17235713 DOI: 10.1245/s10434-006-9216-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2006] [Revised: 08/03/2006] [Accepted: 08/03/2006] [Indexed: 12/27/2022]
Abstract
BACKGROUND Adenocarcinoma of the esophagogastric junction (EGJ) is rapidly increasing in the west. Our aim is to define the prognostic factors and treatment of EGJ carcinoma in Mexico, particularly the location after the Siewert's classification. METHODS A retrospective cohort of patients suffering from EGJ adenocarcinoma treated from 1987 to 2000. The Kaplan-Meier and the Cox's models were used to define prognostic factors. RESULTS Two hundred and thirty-four patients were included, 90 females and 144 males. Surgical resection was possible in 68 cases only (29%). Significant prognostic factors were tumor node metastasis (TNM) stage [stages I-II: risk ratio (RR) is 1; stage III RR is 1.3, 95% confidence interval (CI) 0.75-2.4; stage IV RR, 2.04, 95% CI 1.1-3.7], gender (male RR = 1.47, 95% CI 1.05-2.05), metastatic lymph node ratio (no resection: RR = 1; ratio 0.2-1 RR=0.67, 95% CI 0.39-1.14; ratio 0-0.19 RR = 0.42, 95% CI 0.23-0.76) and seralbumin (3 mg/dL or less RR = 2.05 95% CI 1.3-3.2; 3.1-3.4 mg/dL RR = 1.9 95% CI 1.2-3.03; 3.5-3.8 mg/dL RR = 1.3 95% CI 0.8-1.9; 3.9 mg/dL or more: RR = 1) (model P = 0.0001). CONCLUSIONS EGJ adenocarcinoma is a highly lethal neoplasia and the location after the Siewert' classification is not a prognostic factor. In Mexico, TNM clinical stage, serum albumin, gender, surgical resection and metastatic lymph node ratio are significant prognostic factors. Curative treatment is infrequent but radical resection is associated to longer survival. Consequently, the management must consider quality of life and surgical morbidity.
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Affiliation(s)
- Luis F Oñate-Ocaña
- Clínica de Neoplasias Gástricas, Gastroenterology Department, Surgery Division, Instituto Nacional de Cancerología, México D.F., México.
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Bollschweiler E, Baldus SE, Schröder W, Schneider PM, Hölscher AH. Staging of esophageal carcinoma: length of tumor and number of involved regional lymph nodes. Are these independent prognostic factors? J Surg Oncol 2006; 94:355-63. [PMID: 16967455 DOI: 10.1002/jso.20569] [Citation(s) in RCA: 125] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND OBJECTIVES New potential prognostic indicators aside from the TNM classification have been proposed. The aim of this study was to analyze the prognostic relevance of tumor length as well as number of involved regional lymph nodes (LNM) in patients with esophageal carcinoma. METHODS Two hundred thirteen patients with esophageal carcinoma (116 squamous cell- and 97 adenocarcinoma) were included in this study. Treatment of choice was subtotal en bloc esophagectomy including "2-field" lymphadenectomy. The median number of examined lymph nodes (LNs) was 28. Eighty patients (38%) received preoperative radio-chemotherapy according to a standardized protocol. Histopathology consisted of tumor stage, residual tumor, grading, and number of examined and involved LN. Univariate and multivariate prognostic values were calculated. RESULTS Length of tumor correlated with pT/ypT-category (P<0.01). Univariate but not multivariate analysis showed better survival for tumors<or=3 cm (P<0.05). Patients with 1-5 LNM had significantly better prognoses than those with more than 5 LNM (Hazard ratio 2.7, 95% CI=1.7-4.2) (P<0.01). Patients without LNM and more than 15 examined LN showed significantly better prognosis than those with fewer examined LN (Hazard ratio=0.3, 95% CI=0.1-0.6) (P<0.01). CONCLUSIONS A revision of the TNM classification for esophageal carcinoma should subdivide the pN1-category according to the number of LNM.
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Pramesh CS, Mistry RC, Jambhekar NA, Laskar SG. Does the TNM staging system for esophageal cancer need revision? J Am Coll Surg 2006; 202:855-6; author reply 856. [PMID: 16648030 DOI: 10.1016/j.jamcollsurg.2006.02.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2006] [Accepted: 02/06/2006] [Indexed: 11/19/2022]
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Bombardieri E. The added value of metabolic imaging with FDG-PET in oesophageal cancer: prognostic role and prediction of response to treatment. Eur J Nucl Med Mol Imaging 2006; 33:753-8. [PMID: 16733687 DOI: 10.1007/s00259-006-0147-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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