Prognostic Value of Extranodal Extension on Imaging Studies in Oropharyngeal, Laryngeal, and Hypopharyngeal Cancers Treated By Primary Chemoradiation

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The 8th edition of AJCC staging system has incorporate extranodal extension (ENE) status into one of staging criteria. The importance of ENE in pathologic staging has been confirmed. However, the evidence of prognostic value of ENE in imaging studies is not sufficient. Therefore, we raised this study to evaluate the prognostic value of extranodal extension on imaging studies (iENE) in oropharyngeal, laryngeal, and hypopharyngeal cancers treated by primary chemoradiation. This study reviewed cancer registry data of our hospital from 2005 to 2014 with following inclusion criteria: oropharyngeal, laryngeal, and hypopharyngeal cancers which were diagnosed by pathologic examination, stage III or IV (7th edition of AJCC staging system), treated by concurrent chemoradiation therapy, and available CT or MRI for reviewing iENE status. Patients who had evident metastatic disease, previous cancer history, and inadequate treatment were excluded from analysis. Images for staging work-up were reviewed by 2 radiologists. The criteria of iENE were: clear infiltration of adjacent fat or muscles, irregular nodal surface, or irregular capsular enhancement. Clinical stage (7th edition of AJCC staging system), iENE status, and clinical outcome were recorded and analyzed. Because the registry data were recorded before 2018, there was information of human papillomavirus (HPV) status for oropharyngeal cancer. The primary end point was recurrence-free survival (RFS). In total, 846 patients were selected for analysis. Presence of iENE correlated with more nodal recurrence in hypopharyngeal and laryngeal cancer and distant metastasis in oropharyngeal cancer (chi-square test, 2-sided, < 0.05). When there were no iENE, the 3-year RFS rates were 73.8%, 70.3%, and 64.3% for oropharyngeal cancer, hypopharyngeal cancer, and laryngeal cancer, respectively. The 3-year RFS rates were 62%, 57.7%, and 49.7% for oropharyngeal cancer, hypopharyngeal cancer, and laryngeal cancer, respectively, if iENE was identified in image studies. Univariate analysis revealed that clinical T stage, clinical N stage, stage grouping, and iENE status correlated with RFS (p < 0.05) in oropharyngeal and hypopharyngeal cancer. In laryngeal cancer, only iENE status correlated with RFS but the significance was marginal (p = 0.08). In multivariate analysis, clinical T4, clinical N3, and iENE indicated poor RFS independently in hypopharyngeal cancer. Only clinical N3 was independent prognostic factor in oropharyngeal cancer. iENE status is an important prognostic factor and correlated with more tumor recurrence and inferior RFS in hypopharyngeal cancer and laryngeal cancer treated by chemoradiation therapy. The prognostic value of iENE is more ambiguous in oropharyngeal cancer but lack of HPV status in oropharyngeal cancer may lead to this result. Further evaluation for oropharyngeal cancer with HPV status is indicated.