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Journal of Clinical Oncology, Vol 25, No 7 (March 1), 2007: pp. 907-908 © 2007 American Society of Clinical Oncology. DOI: 10.1200/JCO.2006.10.3770
It Is Time for a Proper Staging System for Adenocarcinoma of the Gastroesophageal JunctionDepartment of Human Pathology and Oncology, Unit of Surgical Oncology, University of Siena, Italy
Department of General Surgery, University of Verona, Italy
Department of Human Pathology and Oncology, Unit of Surgical Oncology, University of Siena, Italy
Department of Human Pathology and Oncology, Unit of Surgical Oncology, University of Siena, Italy To the Editor: We read with great interest the article by Lagarde and colleagues entitled "Prognostic Factors in Adenocarcinoma of the Esophagus or Gastroesophageal Junction."1 As stated by the authors themselves, gastroesophageal junction (GEJ) adenocarcinoma is considered as a distinct clinical entity by the majority of authors, and the adequacy of the current TNM staging system has been questioned repeatedly; nonetheless, so far it has not been considered as a specific neoplasm in the International Union Against Cancer and American Joint Committee on Cancer guidelines.2 According to the present TNM staging system, adenocarcinomas of the GEJ are classified as esophageal if more than 50% of the tumor mass involves the esophagus and as gastric if more than 50% involves the stomach.2 While staging of tumors with the center clearly located in the distal esophagus or in the subcardial region is undemanding, classification problems arise for true junctional tumors because of their borderline location. Furthermore, many differences exist between subcardial gastric adenocarcinoma and stomach cancer as well as between adenocarcinoma of the distal esophagus and tumors of the thoracic esophagus. Siewert et al3 proposed an anatomotopographic classification for adenocarcinomas involving the GEJ which considers three types of tumors that, as already reported by Lagarde et al, did not show prognostic significance per se. The authors analyzed a great number of prognostic factors and concluded that although TNM parameters have the advantage of the simplicity, they do not seem to completely reflect the biologic diversity of GEJ adenocarcinoma and that additional factors can improve staging. In accordance with Lagarde et al and with many other authors, we firmly believe that GEJ adenocarcinoma needs a peculiar classification that differs both from esophageal and gastric staging systems. But, it is our own idea that, at the moment, depth of tumor invasion (pT), nodal involvement (pN), and presence of distant metastasis (M) together with residual tumor (R) are the main prognostic factors in gastrointestinal tumors and that TNM staging system certainly remains the most valid tool to stage esophageal as well as gastric carcinoma; particularly, no clinical, histopathologic, or biologic markers have been yet identified to have a comparable prognostic value. While the article by Lagarde et al openly highlighted the unquestionable importance of R-category, it is our idea that the necessity of considering GEJ adenocarcinoma separately from esophageal and gastric carcinoma in International Union Against Cancer and American Joint Committee on Cancer guidelines should have been stressed more strongly. In addition, we believe that some peculiar issues on staging of this neoplasia should be considered: (1) depth of tumor invasion; several articles reported a similar prognosis between pT2 and pT3 subsets.4,5 This result seems to be due to the lack of the serosa in the GEJ region. Accordingly, some authors proposed to classify tumors with transmural growth and invasion of perigastric fat as pT2b and group this subset with pT3 tumors. (2) Nodal involvement; considering univariate survival analysis, both pT and pN classes usually result to be strong predictor of survival, otherwise, limiting the analysis to paper offering multivariate analysis, nodal involvement results to overweight the importance of pT class.5-8 In our series, Cox regression analysis showed lymph node involvement to be significantly the most important prognostic factor.5,9 (3) Number of nodal metastasis; as well described in the article by Lagarde et al, the number of metastatic nodes is a strong and an independent predictor of survival. Among the analyzed studies, an unfavorable prognosis has been reported for patients with more than three to six affected nodes.7-10 Gastric cancer pN staging system already considers the number of involved nodes, while a number-based revision of esophageal pN staging system has been proposed by several authors.11-13(4) Site of nodal metastasis; celiac nodes are regarded as metastatic by TNM staging system for esophageal cancer. The review by Lagarde et al refers to the site of nodal metastasis as a minor prognostic factor. No study considered in the article analyzing the importance of location of positive nodes reports a lack of prognostic effect for nonregional lymph nodes. Particularly, the reported findings showed that patients with nodal metastasis outside the regional nodes had a poorer prognosis with respect to patients with regional node metastasis, even though better with respect to cases with systemic involvement.13,14 To our knowledge, no study except ours, has been published specifically correlating a number- and a site-based classification in GEJ adenocarcinoma.9 In our series, even among patients with a similar number of involved lymph nodes, the site of metastasis was found to be a strong and independent predictor of survival. Furthermore, we recently published our experience demonstrating that virtually no chance of survival is observed for patients with involvement of lymph nodes other than perivisceral.15 We demonstrated that patients with more than six metastatic nodes or involvement of second-tier nodes or beyond have little chance of survival and that the influence on survival showed by the Japanese Gastric Cancer Association as well as by the TNM staging systems was adequately represented after combining the two classifications. Consequently, the classes of the above mentioned classifications were joined together to build up a new pN classification which considers four categories: pN0, patients with fewer than seven metastatic nodes located within the first tier, patients with more than six involved nodes or involvement of second tier or beyond, and M1a.15 Finally, we would sincerely congratulate with Lagarde and colleagues for their great contribution to a better knowledge of this extremely aggressive disease in addition to advocate the refining of a proper staging system for GEJ adenocarcinoma. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The authors indicated no potential conflicts of interest. REFERENCES
1. Lagarde SM, ten Kate FJ, Reitsma JB, et al: Prognostic factors in adenocarcinoma of the esophagus or gastroesophageal junction. J Clin Oncol 24:4347-4355, 2006 2. Sobin LH, Wittekind C International Union Against Cancer (UICC): TNM Classification of Malignant Tumours (ed 5). New York, NY, John Wiley & Sons, 1997 3. Siewert JR, Feith M, Werner M, et al: Adenocarcinoma of the esophagogastric junction: Results of surgical therapy based on anatomical/topographic classification in 1,002 consecutive patients. Ann Surg 232:353-361, 2000[CrossRef][Medline] 4. Siewert JR, Bottcher K, Stein HJ, et al: Problem of proximal third gastric carcinoma. World J Surg 19:523-531, 1995[CrossRef][Medline] 5. de Manzoni G, Pedrazzani C, Pasini F, et al: Results of surgical treatment of adenocarcinoma of the gastric cardia. Ann Thorac Surg 73:1035-1040, 2002 6. Blomjous JG, Hop WC, Langenhorst BL, et al: Adenocarcinoma of the gastric cardia: Recurrence and survival after resection. Cancer 70:569-574, 1992[CrossRef][Medline] 7. Wayman J, Bennett MK, Raimes SA, et al: The pattern of recurrence of adenocarcinoma of the oesophago-gastric junction. Br J Cancer 86:1223-1229, 2002[CrossRef][Medline] 8. Mariette C, Castel B, Toursel H, et al: Surgical management of and long-term survival after adenocarcinoma of the cardia. Br J Surg 89:1156-1163, 2002[CrossRef][Medline] 9. de Manzoni G, Pedrazzani C, Verlato G, et al: Comparison of old and new TNM classification systems for nodal staging of adenocarcinoma of the gastro-oesophageal junction. Br J Surg 91:296-303, 2004[CrossRef][Medline] 10. Nigro JJ, DeMeester SR, Hagen JA, et al: Node status in transmural esophageal adenocarcinoma and outcome after en bloc esophagectomy. J Thorac Cardiovasc Surg 117:960-966, 1999 11. Rice TW, Blackstone EH, Rybicki LA, et al: Refining esophageal staging. J Thorac Cardiovasc Surg 125:1103-1110, 2003 12. Eloubedi M, Desmond R, Arguedas MR, et al: Prognostic factors for the survival of patients with esophageal carcinoma in the US. Cancer 95:1434-1443, 2002[CrossRef][Medline] 13. Korst RJ, Rusch VM, Venkatraman E, et al: Proposed revision of the staging classification for esophageal cancer. J Thorac Cardiovasc Surg 115:660-669, 1997 14. Steup WH, De Leyn P, Deneffe G, et al: Long-term survival in relation to the pattern of lymph node metastasis and a critical analysis of the accuracy or inaccuracy of pTNM classification. J Thorac Cardiovasc Surg 111:85-94, 1997 15. Pedrazzani C, de Manzoni G, Marrelli D, et al: Nodal staging in adenocarcinoma of the gastro-esophageal junction: Proposal of a specific staging system. Ann Surg Oncol 10.1245/s10434-006-9094-9 [epub ahead of print on December 5, 2006]
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Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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