CEA as a pharmacodynamic biomarker for metastatic anal cancer.

684 Background: While carcinoembryonic antigen (CEA) as a tumor marker is frequently used in the management of colorectal adenocarcinoma, its clinical utility in squamous cell carcinoma of the anus (SCCA) has never been reported. Indeed, no tumor markers have been validated for monitoring tumor burden in the course of any HPV-associated malignancy like SCCA. We hypothesized that CEA levels might be preferentially elevated in patients with metastatic SCCA. Methods: Charts from 212 patients with SCCA were reviewed under an IRB-approved protocol for correlations between CEA levels and corresponding oncologic status. Clinical status was categorized as newly diagnosed non-metastatic (D), after chemoradiation with no evident remnant disease (N), recurrent/resectable SCCA (R), locally advanced/unresectable SCCA (U), metastatic SCCA to lymph nodes only (M-LN), or metastatic SCCA to visceral organs (M-V). Mean CEA levels were compared between subgroups via student t-tests, and frequencies of elevated CEA were compared via Chi-squared analyses. Results: 118 SCCA patients had metastatic disease (98 M-V, 19 M-LN). Mean CEA levels by clinical status were 5.4 (D), 2.0 (N), 2.3 (R), 4.6 (U), 6.0 (M-LN), and 22.2 (M-V), with a higher (statistically insignificant) mean CEA level in the M-V relative to other populations. However, patients with visceral metastases were more likely to have an elevated CEA at presentation (40.4%) relative to patients with newly diagnosed, non-metastatic SCCA (17.6%, p = .07) or recurrent SCCA (11.1%, p = .02). For patients with metastatic SCCA, a significant association existed between change in CEA and corresponding change in radiographic tumor dimensions (OR 24, p < 0.0001). Conclusions: Trends in CEA correlate with dynamic changes in tumor burden for patients with metastatic SCCA, and patients with metastatic SCCA were more likely to have an elevated CEA. Given that immune checkpoint blockade agents like nivolumab have proven benefit for metastatic SCCA, these data provide rationale for use of newer generation immunotherapeutic approaches like CEA-T cell bispecific antibodies, which target CEA-expressing tumors, in clinical trials for patients with metastatic SCCA.