# Liver Metastasectomy in Anal Squamous Cell Carcinoma: The Mayo Clinic Experience

## TL;DR

This study shows that liver-directed surgery can significantly improve survival for rare cases of anal cancer that has spread only to the liver.

## Contribution

The study provides novel evidence that liver-directed therapy in carefully selected patients with liver-only metastatic anal squamous cell carcinoma can achieve prolonged survival.

## Key findings

- Patients undergoing liver-directed therapy had a median overall survival of 51.3 months, exceeding historical outcomes.
- Most recurrences occurred within the liver despite curative-intent treatment.
- Poorly differentiated tumor histology was associated with worse survival outcomes.

## Abstract

Metastatic squamous cell carcinoma of the anus remains a rare disease with poor prognosis, and evidence guiding the management of liver-limited metastatic disease is sparse. While platinum-based chemotherapy with immunotherapy represents the current standard of care, long-term survival remains uncommon. The role of metastasis-directed therapy in this population is not well defined, with existing data largely restricted to small series. In this single-institution retrospective cohort study spanning three decades, we report outcomes for 25 patients with liver-only metastatic anal squamous cell carcinoma who underwent curative-intent liver-directed therapy. We demonstrate a median overall survival of 51.3 months, substantially exceeding historical outcomes reported with systemic therapy alone and prior multi-institutional surgical series. Our data suggested that liver-directed therapy may be associated with favorable outcomes in highly selected patients.

Background: Metastatic squamous cell carcinoma of the anus (SCCA) carries a poor prognosis, with systemic therapy remaining the standard of care. While metastasis-directed therapy improves outcomes in select gastrointestinal malignancies, the role of liver-directed intervention in metastatic SCCA remains undefined. We evaluated clinicopathologic features and oncologic outcomes of patients with liver-limited metastatic SCCA treated with curative-intent hepatic local therapy at a tertiary academic center. Methods: We conducted a retrospective cohort study of adults with histologically confirmed SCCA and liver-only metastatic disease who underwent curative-intent hepatic resection or ablation at Mayo Clinic between 1993 and 2023. Patients with extrahepatic disease or incomplete records were excluded. Demographic, tumor, treatment, and outcomes data were abstracted from electronic medical records. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan–Meier method. Prognostic factors were assessed using univariate Cox proportional hazards models. Results: Twenty-five patients met inclusion criteria. Median age was 56.7 years, and 92% were female. Most patients had metachronous metastases (76%), a single hepatic lesion (56%), and unilobar disease (76%). Pre-intervention systemic therapy was administered in 52% of patients, with radiographic complete or partial responses observed in all treated patients. Liver-directed therapy consisted of surgical resection in 80% and thermal ablation in 20%. Among surgical patients, 90% achieved microscopically negative margins. With a median follow-up of 22 months, disease recurrence occurred in 80% of patients, most commonly within the liver. Median DFS was 7.27 months. Median OS from the date of liver-directed therapy was 51.3 months. On univariate analysis, poorly differentiated tumor histology was associated with inferior OS (hazard ratio 4.67, p = 0.018). No other clinicopathologic variables were significantly associated with DFS or OS. Conclusions: In this single-institution experience, carefully selected patients with liver-limited metastatic SCCA undergoing curative-intent hepatic-directed therapy achieved prolonged overall survival, substantially exceeding historical outcomes with systemic therapy alone. Despite frequent recurrence, the observed median OS exceeding four years supports consideration of liver-directed therapy within a multidisciplinary framework for patients demonstrating favorable disease biology and response to systemic treatment. Prospective studies are needed to better define patient selection and optimal integration of local and systemic therapies in the modern treatment era.