Prognostic importance of radiologic extranodal extension in nasopharyngeal carcinoma treated in a Canadian cohort

To confirm the prognostic value of radiologic extranodal extension (rENE) and its role in clinical-N classification in nasopharyngeal carcinoma (NPC) treated in a western institution.NPC treated between 2010 and 2017 were included. Pre-treatment MRI were reviewed for unequivocal rENE and its grade: grade-1: tumour invading through any nodal capsule but confined to perinodal fat; grade-2: ≥2 adjacent nodes forming a coalescent nodal mass; grade-3: tumour extending beyond perinodal fat to invade/encase adjacent structures. Overall survival (OS) and disease-free survival (DFS) were compared between rENE-positive (rENE+) and rENE-negative (rENE-) patients. Multivariable analysis (MVA) confirmed the prognostic importance of rENE and its grade. Staging schemas including rENE in N-classification were proposed and their performance evaluated.A total of 274 patients were eligible (43 cN0; 231 cN-positive). rENE was identified in 83/231 (36%) cN-positive, including grade 1/2/3 rENE in 14/58/11 cases. Compared to rENE-, rENE+ patients had a lower OS (68% vs 89%, p < 0.001) and DFS (58% vs 80%, p < 0.001). MVA confirmed the prognostic importance of grade-2 [HR: OS: 2.85 (p = 0.005); DFS: 2.89 (p < 0.001)] and grade-3 rENE [HR: OS 5.28 (p = 0.004); DFS 3.86 (p = 0.005)], with a trend for grade-1 vs rENE- [HR: OS 2.63 (p = 0.13); DFS 1.49 (p = 0.520)]. We evaluated classifying any rENE as cN3 (Proposal-I) or any grade-2/grade-3 rENE as cN3 (Proposal-II). The stage schema with Proposal-I cN-classification ranked the highest in the performance evaluation.rENE is an important prognostic factor in this western NPC cohort. We propose classifying any unequivocal rENE as cN3.