Objective To analysis the predictive factrors for pathologic complete response (pCR) and prognosis after neoadjuvant therapy of locally advanced gastric cancer.

Methods The retrospective cohort study was conducted. The clinicopathological data of 662 patients with locally advanced gastric cancer who underwent neoadjuvant therapy in 12 medical centers, including Fudan University Shanghai Cancer Center, et al, from January 2018 to October 2023 were collected. There were 493 males and 169 females, aged 63(range, 24-82)years. After neoadjuvant therapy, there were 331 patients with pCR and 331 patients without pCR. Observation indicators: (1) clinical characteristics of pCR and non-pCR patients after neoadjuvant therapy; (2) predictive factors for pCR after neoadjuvant therapy; (3) prognosis after neoadjuvant therapy; (4) prognostic factors analysis after neoadjuvant therapy. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the nonparameter rank sum test. Count data were represented as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Logistic regression model was used to identify predictive factors for pCR. The Kaplan-Meier method was used to plot the survival curve and calculate the survival rate. The survival analysis was conducted using the Log-Rank test. The COX proportional risk regression model was used for univariate and multivariate analyses.

Results (1) Clinical characteristics of pCR and non-pCR patients after neoadjuvant therapy. There were significant differences in the serum oncolo-gical indicators, tumor diameter, signet ring cell carcinoma, surgical procedures, neoadjuvant therapy pattern, postoperative N staging between pCR and non-pCR patients (P<0.05). (2) Predictive factors for pCR after neoadjuvant therapy. Logistic regression analysis showed that serum oncological indi-cators, signet ring cell carcinoma and neoadjuvant therapy pattern were independent predictive factors for pCR after neoadjuvant therapy in locally advanced gastric cancer odds ratio=0.479, 0.290, 1.451, 95% confidence interval (CI) as 0.333-0.691, 0.146-0.576, 1.199-1.756, P<0.05. (3) Prognosis after neoadjuvant therapy. All the 662 patients were followed up for 21.0(range, 0.7-109.0)months. The overall survival rates were 88.2% and 69.8% for pCR and non-pCR patients, showing a significant difference between them (hazard ratio=0.351, 95%CI as 0.228-0.431, P<0.05). The disease-free survival rates were 87.3% and 61.9% for pCR and non-pCR patients, showing a significant difference between them (hazard ratio=0.285, 95%CI as 0.226-0.416, P<0.05). Further analysis: among the patients with negative lymph node metastasis after surgery, the overall survival rates were 90.4% and 69.8% for pCR and non-pCR patients, showing a significant difference between them (hazard ratio=0.292,95%CI as 0.237-0.475, P<0.05). The disease-free survival rates were 87.7% and 58.3% for pCR and non-pCR patients, showing a significant difference between them (hazard ratio=0.279, 95%CI as 0.232-0.431, P<0.05). Among the patients with positive lymph node metastasis, the overall survival rates were 74.4% and 69.8% for pCR and non-pCR patients, showing no significant difference between them (hazard ratio=0.671, 95%CI as 0.404-1.231, P>0.05). The disease-free survival rates were 71.8% and 61.9% for pCR and non-pCR patients, showing no significant difference between them (hazard ratio=0.628, 95%CI as 0.403-1.122, P>0.05). Of pCR patients after neoadjuvant therapy, the overall survival rates were 87.8% and 89.7% for patients with and without postoperative adju-vant therapy, showing no significant difference between them (hazard ratio=0.710, 95%CI as 0.268-1.693, P>0.05). The disease-free survival rates were 85.9% and 88.2% for patients with and without postoperative adjuvant therapy, showing no significant difference between them(hazard ratio=0.919, 95%CI as 0.417-2.010, P>0.05). (4) Prognostic factors analysis after neoadjuvant therapy. Results of multivariate analysis showed that tumor diameter, postoperative N staging, pCR status were inde-pendent influencing factors for overall survival time after neoadjuvant therapy in locally advanced gastric cancer (hazard ratio=1.476, 2.691, 0.621, 95%CI as 1.042-2.092, 1.730-3.965, 0.406-0.948, P<0.05). Serum oncological indicators, tumor diameter neoadjuvant therapy pattern, postoperative N staging, pCR status were independent influencing factors for disease-free survival time after neo-adjuvant therapy in locally advanced gastric cancer (hazard ratio=1.477, 1.474, 0.780, 2.182, 0.472, 95%CI as 1.080-2.020, 1.069-2.030, 0.635-0.958, 1.509-3.154, 0.316-0.704, P<0.05).

Conclusions Serum oncological indicators, signet ring cell carcinoma, and neoadjuvant therapy pattern are inde-pendent predictive factors for pCR after neoadjuvant therapy in locally advanced gastric cancer. The locally advanced gastric cancer patients with pCR after neoadjuvant therapy have better prognosis than patients with non-pCR. The survival benefits are more prevalent in pCR patients with negative lymph node metastasis after surgery, while the benefits in pCR patients with positive lymph node metastasis after surgery are comparable to non-pCR patients. Aadjuvant therapy after surgery may not improve the prognosis of pCR patients after neoadjuvant therapy. The pCR status is an indepen-dent influencing factor for overall survival and disease-free survival time after neoadjuvant therapy in locally advanced gastric cancer.