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 2017-2021. 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.