Combination of tumor markers predicts progression and pathological response in patients with locally advanced gastric cancer after neoadjuvant chemotherapy treatment

BACKGROUND: The prognostic values of preoperative tumor markers (TMs) remain elusive in patients with locally advanced gastric cancer (LAGC) after neoadjuvant chemotherapy treatment (NACT). This study aimed to assess and establish a novel scoring system incorporating carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 72-4 (CA72-4) to enhance prognostic accuracy for progression-free survival (PFS) and pathological response (pCR). METHODS: Patients' data were retrospectively analyzed from December 2006 to December 2017 in our center. The cutoff value of TMs was determined using the time-dependent receiver operating test characteristics method. These three TMs were allocated 1 point each for the post neoadjuvant chemotherapy combination of tumor markers (post-NACT CTM) scores. The training group comprised 533 patients, responsible for full analysis, and the validation group comprised 137 patients based on the selection protocol. RESULTS: Of 533 enrolled patients, 138, 233, 117, and 45 patients scored 0, 1, 2, 3 respectively. The 3-year PFS rate Multivariate analysis revealed that post-NACT CTM score was an independent predictor of PFS (0 vs. 1, HR: 1.34, 95% CI: 0.92-1.96, P = 0.128; 0 vs. 2, HR: 2.03, 95% CI: 1.35-3.05, P = 0.001; 0 vs. 3, HR: 2.98, 95% CI: 1.83-4.86, P < 0.001). The time-dependent area under curve (AUC) revealed a consistent highest level for post-NACT CTM than other three single TMs. Lower post-NACT CTM score significantly correlated with higher pCR rate based on multivariate logistic regression (2/3 vs. 1, OR: 2.77, 95% CI: 0.90-8.53, P = 0.077; 2/3 vs. 0, OR: 4.33, 95% CI: 1.38-13.61, P = 0.012). A nomogram was formed with both internal and external validation. CONCLUSIONS: The post-NACT CTM score system served as a strong independent predictor for PFS and pCR in LAGC patients who received NACT. Further population-based studies are required to confirm our results.