Imaging-detected extranodal extension (iENE) upstages HPV+ OPC but only modestly improves TNM9 risk separation

In this secondary analysis of the Phase III NRG/RTOG 1016 HPV-mediated (p16+) oropharyngeal cancer trial (NCT01302834), pretreatment CT simulation scans were reread by 2 expert head-and-neck radiologists to adjudicate iENE in clinically node-positive patients (n=586; 60% iENE+; median follow-up 4.2 years). iENE+ disease was independently prognostic for worse outcomes: 5-year OS 79.2% vs 87.0% (HR 1.63, 95% CI 1.04–2.56) and 5-year PFS 68.8% vs 80.4% (HR 1.78, 95% CI 1.24–2.57). However, the TNM9 cN schema that upstages iENE+ by one stratum performed similarly to TNM8 overall (C-index 0.72 vs 0.73; AIC 1112.70 vs 1109.34), suggesting limited net gain in discrimination in this prospective dataset—even though iENE itself tracks with worse survival (and the cohort’s baseline outcomes are in the ballpark of modern definitive cisplatin-RT benchmarks from RTOG 1016 overall, with ~85% 5-year OS in the cisplatin arm).