Development of evidence‐based post‐treatment surveillance guidelines in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is limited by comprehensive documentation of patterns of recurrence and metastatic spread.

A retrospective analysis of patients diagnosed with R/M HNSCC at a National Cancer Institute‐designated cancer center between 1998– 2019 was performed (n = 447). Univariate and multivariate analysis identified patterns of recurrence and predictors of survival.

Median overall survival (mOS) improved over time (6.7 months in 1998–2007 to 11.8 months in 2008–2019, p = .006). Predictors of worse mOS included human papillomavirus (HPV) negativity (hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.2–2.6), high neutrophil/lymphocyte ratio (HR, 2.1 [1.4–3.0], disease‐free interval (DFI) ≤6 months (HR, 1.4 [1.02–2.0]), and poor performance status (Eastern Cooperative Oncology Group, ≥2; HR, 1.91.1–3.4). In this cohort, 50.6% of recurrences occurred within 6 months of treatment completion, 72.5% occurred within 1 year, and 88.6% occurred within 2 years. Metachronous distant metastases were more likely to occur in patients with HPV‐positive disease (odds ratio [OR], 2.3 [1.4–4.0]), DFI >6 months (OR, 2.4 [1.5–4.0]), and body mass index ≥30 (OR, 2.3 [1.1–4.8]). Oligometastatic disease treated with local ablative therapy was associated with improved survival over polymetastatic disease (HR, 0.36; 95% CI, 0.24–0.55).

These data regarding patterns of distant metastasis in HNSCC support the clinical utility of early detection of recurrence. Patterns of recurrence in this population can be used to inform individualized surveillance programs as well as to risk‐stratify eligible patients for clinical trials.

• After treatment for head and neck cancer (HNC), patients are at risk of recurrence at prior sites of disease or at distant sites in the body.
• This study includes a large group of patients with recurrent or metastatic HNC and examines factors associated with survival outcomes and recurrence patterns.
• Patients with human papillomavirus (HPV)‐positive HNC have good survival outcomes, but if they recur, this may be in distant regions of the body and may occur later than HPV‐negative patients.
• These data argue for personalized follow‐up schedules for patients with HNC, perhaps incorporating imaging studies or novel blood tests.