As we collectively gain a greater understanding of the biology of cancers, the number of factors conveying prognostic significance will continue to expand and may become incorporated into the traditional TNM staging system. Histologic subtype, gene mutations, expression profiles, micro-RNAs, and single nucleotide polymorphisms are among the factors previously associated with long-term survival. Zhang and colleagues [1Zhang W. Zhu H. Liu X. et al.Epidermal growth factor receptor is a prognosis predictor in patients with esophageal squamous cell carcinoma.Ann Thorac Surg. 2014; 98: 513-520Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar] should be congratulated for the current study investigating the prognostic role of epidermal growth factor receptor (EGFR) expression among patients with esophageal squamous cell carcinoma. As new prognostic factors are evaluated, they must be interpreted in the context of our existing literature. In the current series of 441 patients, 390 (88%) were found to have pathologic T3 to T4a lesions. Despite the large number of patients with advanced T stage tumors, 213 (48%) did not have any lymph node involvement, which appears surprisingly low. The authors also indicated that patient survival could be better predicted by EGFR expression status than by T stage among patients who were pathologically node negative. This finding is impressive and needs to be validated by other studies. Importantly, the current findings are congruent with previous reports indicating the prognostic significance of EFGR expression among patients with esophageal cancer [2Gibson M.K. Abraham S.C. Wu T.T. et al.Epidermal growth factor receptor, p53 mutation and the pathological response predict survival in patients with locally advanced esophageal cancer treated with preoperative chemotherapy.Clin Cancer Res. 2003; 9: 6461-6468PubMed Google Scholar]. Understanding the role of EGFR in esophageal cancer progression is particularly important because of the clinical availability of EFGR targeting agents, and some have been investigated in patients with esophageal cancer. The recently published American College of Surgeons Oncology Group (ACOSOG) Z4051 trial used neoadjuvant cisplatin, docetaxel, and radiotherapy plus the EGFR inhibitor, panitumumab, to prospectively treat patients with locally advanced esophageal adenocarcinoma. A favorable pathologic complete response rate of 33.3% was observed, and an additional 20.4% had a nearly pathologic complete response, defined as less than 10% viability of malignant cells [3Lockhart A.C. Reed C.E. Decker P.A. et al.Phase II study of neoadjuvant therapy with docetaxel, cisplatin, panitumumab plus radiation therapy followed by surgery in patients with locally advanced adenocarcinoma of the distal esophagus (ACOSOG Z4051).Ann Oncol. 2014; ([Epub ahead of print])http://dx.doi.org/10.1093/annonc/mdu091PubMed Google Scholar]. Unfortunately, the induction therapy was fairly toxic and this contributed to a median survival of only 26.3 months. This was substantially lower than the survival observed in the Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) trial, which used only traditional neoadjuvant chemotherapy and radiotherapy [4van Hagen P. Hulshof M.C. van Lanschot J.J. et al.Preoperative chemoradiotherapy for esophageal or junctional cancer.N Engl J Med. 2012; 366: 2074-2084Crossref PubMed Scopus (3580) Google Scholar]. Similar disappointing results were also found with EGFR inhibition in the Eastern Cooperative Oncology Group (ECOF) 2205 trial, which included the addition of cetuximab to oxaliplatin, 5-fluorouracil, and radiotherapy and in the Randomized Trial of EOC With or Without Panitumumab for Advanced and Locally Advanced Esophagogastric Cancer (REAL3) trial where panitumumab was added to standard epirubicin, oxaliplatin and capecitabine for metastatic esophageal cancer [5Kleinberg L.R. Catalano P.J. Gibson M.K. ECOG 2205: a phase II study to measure response rate and toxicity of the neo-adjuvant chemoradiotherapy (CRT)(IMRT permitted) with oxaliplatin (O) and infusional 5-fluorouracil (5FU) plus cetuximab (C225) in patients with operable adenocarcinoma of the esophagus: high risk of post-op adult respiratory distress syndrome (ARDS).Int J Radiot Oncol Biol Phys. 2010; 78: S72Abstract Full Text Full Text PDF PubMed Google Scholar, 6Waddell T.S. Chau I. Barbachano Y. et al.A randomized multicenter trial of epirubicin, oxaliplatin and cepacetabine (EOC) plus panitumumab in advanced esophagogastric cancer (REAL3).J Clin Onocl. 2012; 30 (abst LBA4000)PubMed Google Scholar]. As the role of EFGR is further clarified in esophageal cancers, proper patient selection for targeted therapy may provide improved outcomes in this disease as it has with our current selection criteria for patients with bronchogenic adenocarcinoma. Epidermal Growth Factor Receptor Is a Prognosis Predictor in Patients With Esophageal Squamous Cell CarcinomaThe Annals of Thoracic SurgeryVol. 98Issue 2PreviewOur previous study indicated the survival rate for esophageal squamous cell cancer (ESCC) patients in stage III and positive lymph node groups with postoperative radiation therapy was significantly increased compared with surgery alone. But a predictive biomarker was needed to identify the patients who would benefit from postoperative radiotherapy. This study aims to evaluate epidermal growth factor receptor (EGFR) as an indicator to predict the prognosis of ESCC and to identify the patients who would benefit from postoperative radiotherapy. Full-Text PDF