Trends in surgery and overall survival in non-metastatic anal cancer: A population-based analysis.

3 Background: The incidence of anal cancer has recently exceeded > 10,000 patients/year in the United States. For non-metastatic squamous cell carcinoma of the anal canal (SCCA), concurrent chemoradiotherapy (CRT) followed by abdominoperineal resection (APR) as salvage surgery for non-responders is a key treatment approach. Over the past two decades, findings from phase III trials (RTOG 98-11 and ACT II) have increased our knowledge about appropriate treatment approaches. ACT II indicated that delayed assessment of tumor response and consideration of APR up until 26 weeks is appropriate, as many patients demonstrate delayed response to treatment. Our analysis examines whether current evidence has influenced real-world clinical practice by analyzing trends in rates of primary APR and overall survival (OS) outcomes. Methods: We conducted a retrospective cohort study using data from the Surveillance, Epidemiology, and End Results (SEER) registry, including patients diagnosed with non-metastatic SCCA between 2004 and 2020. Patients with T0 or T1N0 stage disease were excluded. Descriptive statistics were generated, and chi-square tests were used to compare characteristics between patients who underwent surgery and those who did not. Temporal trends in surgery and radiation therapy were analyzed using the Cochrane-Armitage trend test. Multivariable logistic regression was employed to identify factors associated with surgery uptake, while OS trends were analyzed using Kaplan-Meier and Cox proportional hazard models. Results: A total of 16,718 patients were included, with 33.1% requiring salvage APR following CRT. The proportion of patients requiring surgery significantly declined from 46.6% in 2004 to 31.1% in 2020 (p < 0.001). Factors associated with surgery included younger age, male gender, and non-Hispanic Black race (p < 0.001). Kaplan-Meier analysis revealed significant improvements in OS over the study period (log-rank p = 0.0002), with more recent years (2016-2020) associated with significantly better OS compared to earlier periods (2004-2007, HR = 0.77, p < 0.001). Conclusions: The significant decrease in rates of salvage APR for non-metastatic SCCA likely reflects the global impact of recent phase III trials. Meanwhile, OS rates have been steadily improving. These findings suggest improved overall knowledge regarding treatment strategies and highlight the real-world impact of clinical investigation in non-metastatic squamous cell carcinoma of the anal canal.