Associations of Multiple Serum Tumor Markers with Radiological Response and Overall Survival in Patients with Advanced Gastric Cancer Receiving First-Line Palliative Systemic Therapy

Background: Serial serum tumor-marker testing is widely used in clinical practice, but its relationship to concurrent imaging response and survival in advanced gastric cancer (AGC) remains uncertain. We evaluated five serum tumor markers—carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, CA72-4, CA125, and tissue polypeptide antigen (TPA)—in patients receiving first-line palliative systemic therapy. Methods: We retrospectively analyzed 140 patients with unresectable locally advanced or metastatic gastric adenocarcinoma treated between 2021 and 2024. Results: Baseline positivity rates for the individual markers ranged from 43.6% to 73.6%, and at least one marker was elevated in 90.0% of patients. Baseline CA125 positivity was associated with a lower objective response rate compared to CA125 negativity (29.7% vs. 55.3%). Among the 117 patients with complete serial measurements of all five markers, decreases in CEA, CA72-4, CA125, and TPA were more frequent in responders than in nonresponders. Individual marker decreases showed limited discriminatory performance, whereas multi-marker thresholds showed complementary operating characteristics: a decrease in ≥2 markers had a sensitivity of 89.7%, while decreases in all five markers had a specificity of 93.2%. Patients with ≥3 elevated baseline markers had shorter median overall survival than those with <3 elevated markers (8.0 vs. 18.8 months; HR, 2.269; p < 0.001). Conclusions: Multi-marker assessment may provide complementary information at the time of radiological response assessment, but these exploratory findings require prospective and external validation before clinical use.