Background
Anal squamous cell carcinoma is a rare disease with late presentation and heterogenous outcomes. Current staging guidelines do not account for stratification based on metastatic site and number. Therefore, our aim was to evaluate the prognostic relevance of metastasis site in de-novo anal squamous cell carcinoma (ASCC).

Methods
Patients diagnosed with de-novo ASCC were identified from Surveillance, Epidemiology, and End Results (SEER) database. Patients were categorized by metastatic site: only liver, only lung, only non-regional lymph node (LN), only bone, only other, or ≥2 sites. Overall survival was evaluated using Kaplan–Meier methods and multivariable Cox proportional hazards models adjusted for demographics, tumour characteristics, treatment, and socioeconomic factors. Fine-Gray competing risk analyses were also conducted to evaluate cancer specific survival.

Results
Between 2010-2022,13,931 patients with ASCC were identified from the SEER database), of which 971 patients (7%) were M1. This metastatic cohort had a median age of 62 years and showed a female predominance (67%). The median overall survival was 19 months. The number of patients with bone, liver, lung, non-regional LN and ≥2 sites are 29 (2.98%); 155 (15.96%); 49 (5.04%); 246 (25.33%) and 421 (43.35%), respectively. Patients with non-regional LN-only metastases had the best overall survival (36 months), while having ≥2 metastatic sites confers worst prognosis (14 months). On multivariable Cox analysis, compared to non-regional LN-only metastases, mortality risks were significantly higher for liver (HR 1.52, 95% CI 1.13–2.03, p=0.01), lung (HR 1.62, 95% CI 1.07–2.46, p=0.02), bone (HR 2.24, 95% CI 1.35–3.72, p<0.01), and ≥2sites (HR 1.99, 95% CI 1.61–2.46, p<0.001).

Conclusions
The site and number of metastases is an independent prognostic factor in de-novo metastatic ASCC, underscoring the need for site-specific risk stratification to guide clinical decision-making.

Sources of Funding: None to disclose