3473 - Extended-Field Definitive Chemoradiation for Patients with Anal Squamous Cell Carcinoma with Nodal Metastatic Disease

Purpose/Objective(s): Contemporary staging for anal squamous cell carcinoma (ASCC) defines common iliac (CI) and para-aortic (PA) nodal disease as stage IV. This study evaluated oncologic outcomes among patients with metastatic disease limited to these nodal basins. We hypothesized that definitive-intent extended field chemoradiation would be potentially curative for these patients, and that disease limited to CI versus PA nodes would result in distinct patterns of failure, with CI-only disease conferring better outcomes.

Materials/Methods: A single-institution retrospective review identified 53 patients who underwent definitive-intent chemoradiation for newly diagnosed ASCC with nodal disease extending to the CI and/ or PA nodal basins with no other distant metastases. Patient characteristics and disease outcomes (locoregional failure (LRF), distant failure (DF), progression-free survival (PFS), colostomy-free survival (CFS), and overall survival (OS)) were collected. LRF and DF were analyzed by cumulative incidence functions with death as a competing risk whereas survival endpoints were estimated by Kaplan-Meier method. All statistical analyses were performed in R.

Results: From 2013 to 2024, 53 patients (13 male and 40 female), 26 with CI only and 27 with PA nodal involvement, with a median age of 62 years were included. Most (96%) were treated with concurrent 5-fluorouracil/capecitabine and mitomycin. Median radiation doses to the primary tumor and involved CI/PA nodes were 58 Gy and 50 Gy, respectively. With a median follow-up of 26 months, 3-year estimates were 24% for LRF, 27% for DF, 62% for RFS, 63% for CFS, and 74% for OS. Patients with CI nodal involvement, compared to those with PA nodal involvement, had lower rates of DF at 3-years (13% vs 39%, p=0.04) and improved 3-year PFS (74% vs. 53%, p=0.062) and OS (91% vs. 61%, p=0.037). Among all patients, PFS was associated with death without progression (n=1), distant failures (n=10), locoregional failures (n=5), and synchronous failures in multiple locations (n=2, Table 1). Chemoradiation for PA, compared to CI disease, had higher rates of grade 2 (100% vs 85%, p=0.023) but not grade 3 (26% vs 31%, ns) acute non-hematologic toxicity.

Conclusion: Among patients with ASCC with stage IV disease limited to CI or PA lymph nodes, most patients have long-term disease control with chemoradiation. CI nodal disease behaves similarly to locally advanced disease, with low rates of DF. Despite higher rates of DF in PA disease, >50% of patients remained alive and disease free at 3-years. These data demonstrate the feasibility of curative-intent treatment in patients with stage IV ASCC limited to CI or PA lymph nodes.