Prognostic significance of imaging-detected extranodal extension (iENE) in pathological ENE-negative head and neck squamous cell carcinoma.

6079 Background: Advances in perioperative systemic therapy for head and neck squamous cell carcinoma (HNSCC) (e.g., KEYNOTE-689) have increased the need to tailor postoperative management, balancing oncologic benefit against toxicity and resource constraints. Imaging-detected extranodal extension (iENE) has been incorporated as a potential prognostic factor in the UICC TNM 9th edition. However, the prognostic impact of iENE among patients without pathological extranodal extension (pENE) remains unclear. We evaluated the association between iENE status and clinical outcomes in pENE-negative HNSCC. Methods: We retrospectively reviewed patients with HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx, radiologically suspected lymph node metastasis, and underwent primary surgery with neck dissection without adjuvant therapy, between 2012 and 2021. Eligible patients had pathologically confirmed lymph node metastasis, negative surgical margins, and no evidence of pENE. Preoperative iENE status was assessed by board-certified radiologists. Survival endpoints included event-free survival (EFS) and overall survival (OS). Patients were stratified into low-risk (non-candidates for adjuvant therapy) and intermediate-risk (candidates for postoperative radiotherapy alone) groups according to NCCN guidelines. Results: Of 3,771 screened patients, 133 met the eligibility criteria (low-risk: 20, intermediate-risk: 113), of whom 41 (30.8%) were iENE-positive. At a median follow-up of 60.6 months, iENE-positive patients demonstrated poorer outcomes than iENE-negative patients, including shorter EFS (5-year: 33.1% vs 55.4%; hazard ratio [HR], 1.69; p=0.029). The association between iENE positivity and inferior EFS was observed consistently across both risk strata. Overall survival also favored iENE-negative patients (5-year: 80.4% vs. 68.7%). On multivariate analysis, iENE positivity, ECOG Performance Status ≥1, and lower baseline serum albumin were independently associated with poorer EFS. Patients meeting none of the three factors had excellent outcomes despite omission of adjuvant therapy (5-year EFS: 69.8%, 5-year OS: 88.0%). Conclusions: iENE may help identify an unfavorable-prognosis subset among pENE-negative HNSCC patients. The study cohort predates the routine use of perioperative immunotherapy, and the generalizability of these findings in contemporary treatment settings requires prospective validation. Five-year EFS by iENE status: Overall and by risk group. Group iENE status 5y-EFS HR (95% CI) P-value ALL (n = 133) Positive 33.1% 1.69 (1.05-2.71) 0.029 Negative 55.4% Ref. Intermediate risk (n = 113) Positive 34.2% 1.57 (0.94-2.63) 0.08 Negative 51.9% Ref. Low risk (n = 20) Positive 28.6% 3.57 (0.85-15.04) 0.06 Negative 76.9% Ref.