Long-term oncological outcomes after salvage surgery for anal squamous cell carcinoma - a national cohort study

Anal squamous cell carcinoma (ASCC) is an HPV-related tumor primarily treated with concurrent chemoradiotherapy (CRT). Salvage surgery is reserved for patients with residual or recurrent disease following CRT, representing a highly selected, high-risk subgroup. Population-based data on outcomes and prognostic factors after salvage surgery are limited. This study aimed to assess overall survival (OS) and identify prognostic factors in a centralized, national cohort to inform clinical decision-making.

Data were retrospectively collected from the Swedish anal cancer registry and medical charts of all ASCC patients undergoing salvage surgery in Sweden between 2017 and 2021. Survival was analyzed using Kaplan-Meier estimates, log-rank tests, and Cox proportional hazards regression.

Seventy-seven patients underwent salvage surgery with curative intent for residual (n = 34) and recurrent (n = 43) disease. Median age was 64 (IQR 56-73) years, 54 (79%) were HPV-positive and 7 (9%) underwent total pelvic exenteration. R0-resection was achieved in 66 patients (86%), with a 5-year OS of 67.4%, compared with 9.1% for R1-resections (HR 6.16, 95% CI 2.80-13.58). Median follow-up was 46 (IQR 22-65) months. Other factors associated with OS included major 30-day surgical complications (HR = 2.17, 95% CI 1.04-4.54), lymphovascular invasion (HR 2.89, 95% CI 1.25-6.67) and histologically confirmed lymph node metastasis (HR 2.33, 95% CI 1.11-4.86). HPV-status was not associated with survival.

This population-based study shows that long-term survival after salvage surgery is achievable when R0-resection is obtained. Importantly, major postoperative complications were identified as a novel prognostic factor in ASCC. Optimizing R0-resection rates and minimizing complications are key to improving long-term outcomes.