Trends in primary surgery and overall survival in non-metastatic anal cancer: a population-based analysis

BACKGROUND: Anal cancer incidence is rising in the United States, now exceeding 10 000 cases annually. Chemoradiation (CRT) is the standard curative-intent treatment for non-metastatic squamous cell carcinoma of the anus (SCCA), with surgery generally reserved for non-responders with persistent or progressive disease. Recent trials have refined management, supporting the assessment of response at 26 weeks before considering surgery. However, contemporary population-level patterns of upfront primary surgery and associated survival trends remain incompletely described. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) registry (2004-2020), we identified adults with newly diagnosed non-metastatic anal squamous cell neoplasms (ICD-O-3 8050-8089). Outcomes were receipt of primary surgery as initial treatment and overall survival. We evaluated temporal trends (Cochran-Armitage), factors associated with primary surgery (multivariable logistic regression), and survival over time (Kaplan-Meier; multivariable Cox proportional hazards modeling). RESULTS: Among 16 718 patients with non-metastatic anal cancer, 33.1% (n = 5529) underwent primary surgery and 83.7% (n = 13 997) received radiation as part of initial management. Primary surgery declined from 46.0% in 2004 to 28.7% in 2020 (trend P < 0.001), while radiation utilization was relatively stable over time (trend P = 0.106). In adjusted analyses, younger age (<50 vs 60-69 years; OR 1.614), male sex (OR 1.508), and Non-Hispanic Black race (vs Non-Hispanic White; OR 1.178) were associated with higher odds of primary surgery. Tumor factors were strongly associated with surgical use (eg, T1 vs T2: OR 3.072; higher N stage associated with lower odds). Overall survival improved across diagnosis periods (log-rank P = 0.0002); in adjusted Cox models, diagnosis in 2016-2020 (vs 2004-2007) was associated with lower mortality risk (HR 0.77). CONCLUSIONS: From 2004 to 2020, primary surgery as initial management for non-metastatic anal cancer declined substantially, consistent with increasing adoption of CRT, while overall survival improved over time. Persistent use of upfront surgery in select subgroups warrants further study to clarify indications and ensure guideline-concordant care.