Optimum Lymphadenectomy for Esophageal Cancer Methods Worldwide Esophageal Cancer Collaboration Multivariable Risk-adjusted Survival

Objective:Using Worldwide Esophageal Cancer Collaboration data, we sought to (1) characterize the relationship between survival and extent of lymphadenectomy, and (2) from this, define optimum lymphadenectomy. Summary Background Data:What constitutes optimum lymphadenectomy to maximize survival is controversial because of variable goals, analytic methodology, and generalizability of the underpinning data. Methods:A total of 4627 patients who had esophagectomy alone for esophageal cancer were identified from the Worldwide Esophageal Cancer Collaboration database. Patient-specific risk-adjusted survival was estimated using random survival forests. Risk-adjusted 5-year survival was averaged for each number of lymph nodes resected and its relation to cancer characteristics explored. Optimum number of nodes that should be resected to maximize 5-year survival was determined by random forest multivariable regression. Results:For pN0M0 moderately and poorly differentiated cancers, and all node-positive (pN+) cancers, 5-year survival improved with increasing extent of lymphadenectomy. In pN0M0 cancers, no optimum lymphadenectomy was defined for pTis; optimum lymphadenectomy was 10 to 12 nodes for pT1, 15 to 22 for pT2, and 31 to 42 for pT3/T4, depending on histopathologic cell type. In pN+M0 cancers and 1 to 6 nodes positive, optimum lymphadenectomy was 10 for pT1, 15 for pT2, and 29 to 50 for pT3/T4. Conclusions:Greater extent of lymphadenectomy was associated with increased survival for all patients with esophageal cancer except at the extremes (TisN0M0 and ≥7 regional lymph nodes positive for cancer) and well-differentiated pN0M0 cancer. Maximum 5-year survival is modulated by T classification: resecting 10 nodes for pT1, 20 for pT2, and ≥30 for pT3/T4 is recommended.

[1]  V. Rusch,et al.  Worldwide esophageal cancer collaboration. , 2009, Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus.

[2]  N. Altorki,et al.  The Number of Lymph Nodes Removed Predicts Survival in Esophageal Cancer: An International Study on the Impact of Extent of Surgical Resection , 2008, Annals of surgery.

[3]  C. Kennedy,et al.  Does systematic 2-field lymphadenectomy for esophageal malignancy offer a survival advantage? Results from 178 consecutive patients. , 2008, Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus.

[4]  B. Meyers,et al.  Lymph node analysis in esophageal resection: American College of Surgeons Oncology Group Z0060 trial. , 2008, The Annals of thoracic surgery.

[5]  M. Mazumdar,et al.  Total Number of Resected Lymph Nodes Predicts Survival in Esophageal Cancer , 2008, Annals of surgery.

[6]  Matthew Z. Wilson,et al.  Prognostic significance of lymph node metastases and ratio in esophageal cancer. , 2008, The Journal of surgical research.

[7]  G. Sauter,et al.  Is It Time for a New TNM Classification in Esophageal Carcinoma? , 2008, Annals of surgery.

[8]  C. Divino,et al.  Effect of the number of lymph nodes sampled on postoperative survival of lymph node‐negative esophageal cancer , 2008, Cancer.

[9]  C. Mariette,et al.  The Number of Metastatic Lymph Nodes and the Ratio Between Metastatic and Examined Lymph Nodes Are Independent Prognostic Factors in Esophageal Cancer Regardless of Neoadjuvant Chemoradiation or Lymphadenectomy Extent , 2008, Annals of surgery.

[10]  David D. Smith,et al.  Clinical Impact of Lymphadenectomy Extent in Resectable Esophageal Cancer , 2007, Journal of Gastrointestinal Surgery.

[11]  J. Ajani,et al.  Proposed modification of nodal status in AJCC esophageal cancer staging system. , 2007, The Annals of thoracic surgery.

[12]  C. Kang,et al.  Lymphadenectomy extent is closely related to long-term survival in esophageal cancer. , 2007, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[13]  V. Rusch,et al.  The prognostic importance of the number of involved lymph nodes in esophageal cancer: implications for revisions of the American Joint Committee on Cancer staging system. , 2006, The Journal of thoracic and cardiovascular surgery.

[14]  J. Goldblum,et al.  Refining esophageal cancer staging. , 2003, The Journal of thoracic and cardiovascular surgery.

[15]  Cristián Zegers Ariztía,et al.  Manual , 2002 .

[16]  J. Goldblum,et al.  Esophageal carcinoma: depth of tumor invasion is predictive of regional lymph node status. , 1998, The Annals of thoracic surgery.

[17]  Saunders Hs,et al.  Esophageal cancer. Radiologic staging. , 1997 .

[18]  L. Breiman Heuristics of instability and stabilization in model selection , 1996 .

[19]  T. Rösch,et al.  Endosonographic staging of esophageal cancer: a review of literature results. , 1995, Gastrointestinal endoscopy clinics of North America.

[20]  M. Tsurumaru,et al.  Principles of Surgical Treatment for Carcinoma of the Esophagus: Analysis of Lymph Node Involvement , 1981, Annals of surgery.

[21]  Peter D Siersema,et al.  Esophageal cancer. , 2008, Gastroenterology clinics of North America.

[22]  Andy Liaw,et al.  Classification and Regression by randomForest , 2007 .

[23]  Udaya B. Kogalur,et al.  Random Survival Forests for R , 2007 .

[24]  L. Breiman Random Forests , 2001, Machine Learning.

[25]  C. Compton,et al.  AJCC Cancer Staging Manual , 2002, Springer New York.

[26]  D. Ott,et al.  Esophageal cancer. Radiologic staging. , 1997, Radiologic clinics of North America.