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375 Background: Surgery followed by adjuvant radiotherapy (RT) ± systemic therapy (ST) is often recommended for patients (pts) with resectable LA HNSCC with curative intent. This study assessed rwEFS, rwOS, and the correlation between rwEFS and rwOS in elderly pts (≥66 years old at diagnosis) with resected LA HNSCC to better understand unmet needs and inform future clinical trial designs. Methods: This retrospective cohort study utilized linked SEER-Medicare data (2007–2019). Pts with newly diagnosed stage III-IVB (AJCC 6/7th) LA HNSCC (larynx, hypopharynx, oral cavity, or oropharynx) who underwent surgery as primary treatment within 4 months of diagnosis were included. Index date was defined as the primary treatment initiation date. rwEFS was defined as time from index date to first recurrence or death, whichever occurred first. rwOS was defined as time from index date to death. Baseline (12 months prior to index date) factors associated with rwEFS and rwOS were assessed using a Cox proportional hazards model. Correlation between rwEFS and rwOS was assessed using the normal scores rank correlation. Results: A total of 526 pts met the selection criteria (median follow-up: 24.3 months). The median (interquartile range) age at initial diagnosis was 72.6 (68.6-78.8) years, 63.9% were male, 79.5% were white, and 6.1% had stage IVb disease. HPV status and smoking status were not available. Over half of pts received adjuvant RT ± ST following resection. Median rwEFS and 5-year rwEFS were 8.0 months (95% CI: 6.4, 9.2) and 16.3%, respectively. Median rwOS was 32.6 months (95% CI: 26.2, 42.3), with a 5-year rwOS of 37.8%. Older age, primary hypopharynx disease (vs. oropharynx), and higher Charlson Comorbidity Index scores were associated with significantly shorter rwOS. Additionally, surgery followed by RT ± ST (vs. surgery only) and less advanced tumor stage were associated with significantly longer rwEFS and rwOS. The correlation between rwEFS and rwOS was moderate and significantly positive (r = 0.68 [95% CI: 0.62, 0.74], p<0.001). Conclusions: Real-world survival outcomes were modest among elderly pts with surgically managed LA HNSCC, highlighting a population with significant unmet need where more effective therapies are needed. rwEFS was found to have a significant, positive correlation with rwOS, supporting EFS as a predictor for OS in this patient population. Primary treatment and association with rwEFS and rwOS.1,2,3 Treatment Pattern N (%) HR (95% CI) - rwEFS HR (95% CI) - rwOS Surgery Only 144 (27.4%) - - Surgery followed by RT 172 (32.7%) 0.60 (0.47, 0.78)* 0.77 (0.58, 1.03) Surgery followed by RT + ST 128 (24.3%) 0.49 (0.36, 0.66)* 0.50 (0.34, 0.72)* RT or RT+ST followed by surgery 66 (12.5%) 0.66 (0.47, 0.93)* 0.80 (0.55, 1.18) 1Treatment modalities with N<11 were not reported. 2*denotes p < 0.05. 3denotes reference group. [ABSTRACT FROM AUTHOR]