Impact of local therapy on survival among patients with metastatic anal squamous cell carcinoma

4 Background: About 10-20% of patients with anal squamous cell carcinoma (SCCa) present with metastatic disease, and are usually treated with systemic chemotherapy. The role of local therapy to control the primary tumor is controversial in this setting. We evaluated survival impact of local therapy in metastatic anal SCCa. Methods: Data were obtained from all US hospitals that contributed to the National Cancer Database (NCDB) between 2004 and 2015. We excluded patients who did not receive palliative systemic chemotherapy. Univariate (UVA) and multivariable analyses (MVA) were performed to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used to assess the association between tumor/patient characteristics and overall survival (OS). Results: 1,160 patients were identified over 12 years. Median age was 57 years. Majority were female (64.9%), non-Hispanic Whites (79.1%) and had Charlson-Deyo Score of 0 (83.6%). Most common metastatic sites were liver (25.9%), lung (11.6%) and bone (8.5%). More than 79% of the patients received radiation to the primary site, and 10.4% underwent surgical resection for local control. Use of local therapy correlated closely with a significant improvement in OS on MVA (HR 0.66; 0.55-0.79; p < 0.001), with a 12-month and 5-year OS rates of 72.8% and 25.7% respectively, compared with 61.1% and 14.6% for patients treated with chemotherapy only. Poor prognostic factors included male gender (HR 1.44; 1.24-1.67; p < 0.001), age > 70 years (HR 1.28; 1.02-1.62; p = 0.034), lack of health insurance (HR 1.32; 1.02-1.71; p = 0.034), and cloacogenic zone location (HR 4.02; 1.43-11.30; p = 0.008). There was no benefit from abdominoperineal resection (mOS = 19.7mos; HR 1.05; 0.48-2.29; p = 0.909), but both local resection of the primary (mOS = 24.8mos, HR 0.48; 0.29-0.80; p = 0.005) and palliative radiation (mOS = 22.6 mos; HR 0.66; 0.55-0.79; p < 0.001) were associated with improved OS. Conclusions: This is the largest reported study on management of de novo stage IV SCCa. The data suggest that local control of the primary tumor through resection or radiation improved OS in patients with anal SCCa. Patients unlikely to benefit from local therapy include age over 70 years, male, lack of health insurance and cloacogenic carcinoma.