Prognostic value of clinical and radiologic extranodal extension and their role in the 8th edition TNM cN classification for HPV-negative oropharyngeal carcinoma.

Abstract Background/objectives We evaluate the performance between the TNM-8 versus TNM-7 cN-classification and explore the relative prognostic contribution of radiologic extranodal extension (rENE) for HPV-negative oropharyngeal cancer (HPV–OPC). Materials/methods All HPV– OPC treated with IMRT between 2005 and 2016 were included. cENE was defined as unambiguous “fixation” of a neck mass or “skin involvement” on clinical examination. rENE was recorded by re-reviewing pre-treatment CT/MR. Disease-free survival (DFS) stratified by cENE or rENE were compared. Multivariable analyses (MVA) calculated the adjusted hazard ratio (aHR) for the separate cENE and rENE attributes and their combination. A refined cN-category incorporating both cENE and rENE parameters was proposed. The performance of the revision was compared to TNM-8 and TNM-7. Results Of 361 HPV– OPC, 97 were cN0 and 264 were cN+ with 48 cENE+ and 72 rENE+ respectively. Median follow-up was 5.4 years. The 3-year DFS was lower in cENE+ vs cENE-negative (cENE–) (23% vs 45%; aHR = 1.68, p = 0.008) and rENE+ vs rENE-negative (rENE–) patients (29% vs 45%; aHR = 1.44, p = 0.037). The cENE+/rENE+ subset had the worse DFS vs cENE–/rENE+ or cENE–/rENE– (24%/37%/46%, p = 0.005). We propose a refined cN-category wherein any cENE–/rENE+ case is reclassified one N-stratum higher while any cENE+ case remains cN3b. The stage schema with the refined N-categorization outperformed TNM-8, and both outperformed TNM-7. Conclusions cENE and rENE are both prognostic but the cENE+/rENE+ subset has the worst outcome. The TNM-8 cN-categories improves outcome prediction compared to the TNM-7. Incorporation of rENE into TNM-8 cN-categories may further augment performance.