Background: Serum tumor markers have been shown to correlate with the prognosis of gastric cancer (GC); however, the effects of the dynamics of serum tumor markers (cancer antigen (CA)72-4, carcinoembryonic antigen (CEA), CA19-9, CA125, and alpha-fetoprotein (AFP)) on the prognosis of GC before and after neoadjuvant chemotherapy (NACT) remain unclear.

Methods: Data from 334 patients with GC who underwent NACT followed by radical gastrectomy between January 2016 and December 2021 were included in the present study. Tumor marker regression load (ΔTMRL) indicator, including ΔCA72-4, ΔCEA, ΔCA19-9, ΔCA125, and ΔAFP, is defined as [(postNACT marker – preNACT marker) / preNACT marker]. Based on the results of Cox regression analysis, the tumor marker regression load score (TMRLS) was composed of ΔCA72-4, ΔCEA, and ΔCA125. The predictive performance of the nomogram-TMRLS was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC), decision curve analysis (DCA), and C-index.

Results: The patients were divided into two groups, TMRLS-low and TMRLS-high, based on the optimal breakpoint of TMRLS determined in R using the maxstat package. Survival analysis revealed a higher 3-year overall survival (OS) in the TMRLS-low than in the TMRLS-high group (69.8% vs. 34.8%, respectively; P < 0.001). Those in the TMRLS-high group who received postoperative adjuvant chemotherapy (AC) showed a significantly higher 3-year OS rate than those who did not (52.3% vs. 8.3%, respectively; P = 0.020). Multivariate Coxregression analysis indicated that TMRLS was an independent prognostic factor for OS. A nomogram for predicting OS based on TMRLS, ypT stage, ypN stage, and AC showed a significantly higher C-index and AUC than the traditional ypTNM stage (C-index, 0.794 vs. 0.697, respectively; P < 0.001; AUC, 0.827 vs. 0.678, respectively; P < 0.001).

Conclusion: TMRLS appears to be a novel independent prognostic factor for patients with GC who underwent NACT and a radical gastrectomy. Furthermore, the TMRLS-high group, who received postoperative AC, achieved better survival outcomes. Of note, the predictive performance of the nomogram-TMRLS significantly outperformed that of the ypTNM stage.