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.