Threshold Change in CEA as a Predictor of Non-Progression to First-Line Systemic Therapy in Metastatic Colorectal Cancer Patients with Elevated CEA.

Abstract

Carcinoembryonic antigen (CEA) levels are used in conjunction with imaging to monitor response to systemic therapy in metastatic colorectal cancer (mCRC). We sought to identify a threshold for CEA change from baseline to predict progressive disease (PD) in mCRC patients receiving first-line therapy. Patients from trials collected in the ARCAD database were included if baseline CEA was ≥10ng/mL and repeat CEA was available within 14 days of first restaging scan. Optimal cutoffs for CEA change were identified by ROC analysis. Prediction performance of cutoffs was evaluated by sensitivity, specificity, and negative predictive value (NPV). Analyses were conducted by treatment class: chemotherapy alone (chemo), chemotherapy with anti-VEGF antibody (anti-VEGF), and chemotherapy with anti-EGFR antibody (anti-EGFR). 2643 mCRC patients treated with systemic therapy were included. Median percent change of CEA from baseline to first restaging for patients with CR/PR/SD (non-PD) and PD was -53.1% and +23.6% for chemo (n=957), and -71.7% and -45.3% for anti-VEGF (n=1355). The optimal AUC cutoff for differentiating PD from non-PD on first restaging was -7.5% for chemo and -62.0% for anti-VEGF, chemo, ORadj=6.51 (95%CI 3.31-12.83, P < 0.001); anti-VEGF, ORadj=3.45 (95%CI 1.93-6.18, P < 0.001). A 99% NPV clinical cutoff for prediction of non-PD would avoid CT scan at first restaging in 21.0% of chemo and 16.2% of anti-VEGF treated patients. Among patients with SD on first restaging, those with CEA decrease from baseline had statistically significantly improved progression-free and overall survival. Change in CEA from baseline to first restaging can accurately predict non-progression and correlates with long-term outcomes in patients receiving systemic chemotherapy.