Clinicopathologic Features Associated with Survival for Immune Checkpoint Blockade in Patients with Metastatic Anal...

Background/Objectives: Anal cancer is a rare malignancy with limited treatment options. Immune checkpoint inhibitors have shown benefits in some patients with metastatic disease, but predictive factors for immunotherapy response remain undefined. This study retrospectively evaluated clinical and pathological features associated with survival outcomes in metastatic anal cancer treated with immunotherapy. Methods: Data from 105 patients with metastatic anal cancer were analyzed. Kaplan-Meier analysis was used to estimate progression-free survival (PFS) and overall survival (OS), with subgroup comparisons utilizing the Mantel-Cox test. Associations between survival and clinicopathologic features were assessed with Fisher's exact test. Results: Of the patients, 69 (65.7%) received immunotherapy during the first three treatment lines. With a median follow-up of 23.2 months, the median PFS for first-, second-, and third-line systemic therapies was 7.2, 3.7, and 4.7 months, respectively (χ² = 14.2; p < 0.001). In the treatment-refractory setting, median PFS was similar for immunotherapy and chemotherapy: 3.6 months (95% CI, 2.3-4.9) vs. 4.4 months (95% CI, 3.8-5.0), respectively (HR 0.89, 95% CI 0.60-1.3; p = 0.52). Among patients treated with immunotherapy, patients with lymph node-only metastases had significantly prolonged PFS compared to patients with visceral organ involvement (11.3 vs. 3.1 months; HR 0.49, 95% CI 0.21-0.74; p = 0.03). Conclusions: Patients with lymph node-only metastatic anal cancer experienced significantly prolonged PFS with immunotherapy relative to those with involvement of other distant organs, highlighting a distinct subgroup of patients who may benefit from immunotherapy. We also contextualize PFS outcomes across treatment lines for metastatic anal cancer, which can be applied towards the design of future immunotherapy clinical trials.