Squamous cell carcinoma antigen and carcinoembryonic antigen monitoring during post-definitive chemoradiotherapy surveillance for esophageal squamous cell carcinoma: JCOG2106A.

BACKGROUND: Squamous cell carcinoma antigen (SCC-Ag) and carcinoembryonic antigen (CEA) are routinely monitored after definitive chemoradiotherapy (dCRT) for esophageal squamous cell carcinoma (ESCC) in Japan, but their clinical significance remains unclear.

METHODS: We analyzed data from patients with resectable ESCC treated with dCRT in the JCOG0502 and JCOG0909 trials, who underwent intensive protocolized surveillance with computed tomography (CT), esophagogastroduodenoscopy (EGD), SCC-Ag, and CEA. Tumor marker positivity was defined as exceeding the cut-off value at least once, at two consecutive measurements, or at three consecutive measurements during follow-up. Sensitivity and specificity were calculated for SCC-Ag and CEA at 0.1-ng/mL increments to determine whether any cut-off met the predefined performance criteria (sensitivity ≥60% and specificity ≥70%).

RESULTS: This study included 239 patients (stage I/II/III = 147/58/34 [UICC 6th edition]), among whom 38% (91/239) experienced disease progression or recurrence. The median baseline SCC-Ag and CEA levels were 1.0 ng/mL (interquartile range [IQR], 0.8-1.5) and 2.3 ng/mL (IQR, 1.6-3.6), respectively, with a median of 16 measurements each (IQR, 8-19 for SCC-Ag; 8-20 for CEA). The highest specificities with sensitivity ≥60% were 19.6% for SCC-Ag (cut-off, 1.5 ng/mL) and 20.3% for CEA (cut-off, 2.2 ng/mL), but neither met the predefined criteria.

CONCLUSIONS: In this pooled cohort of patients with resectable ESCC who underwent dCRT and intensive protocolized CT and EGD surveillance, routine SCC-Ag and CEA monitoring showed limited incremental diagnostic value. The relevance of these findings to higher-risk cohorts and less intensive surveillance settings warrants further study.