Retrospective analysis of predictive factors for pathological complete response after neoadjuvant chemotherapy in gastric cancer

Abstract

BACKGROUND

Gastric cancer is a malignant tumor with high morbidity and mortality worldwide. Neoadjuvant chemotherapy (NAC), defined as chemotherapy administered before the primary treatment (usually surgery) to reduce tumor size and control micrometastases, has emerged as a crucial therapeutic strategy for locally advanced gastric cancer. Pathological complete response (pCR), characterized by the absence of viable tumor cells in the resected specimen after neoadjuvant treatment, is recognized as a strong predictor of favorable prognosis. However, the factors influencing the achievement of pCR remain incompletely understood.

AIM

To identify and analyze the predictive factors associated with achieving pCR after NAC in gastric cancer patients, thereby providing evidence-based guidance for clinical decision-making.

METHODS

A retrospective analysis was performed on 215 patients from Shandong Cancer Hospital and Tai’an Central Hospital with locally advanced gastric cancer who underwent NAC followed by radical surgery at our hospital between January 2015 and December 2023. Comprehensive clinical and pathological data were collected, including age, gender, tumor location, Lauren classification, clinical staging, chemotherapy regimens, number of chemotherapy cycles, and baseline hematological indicators. The baseline hematological indicators included neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, albumin level, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9. Univariate and multivariate logistic regression analyses were employed to determine the independent predictive factors for pCR.

RESULTS

Among 215 gastric cancer patients, 41 (19.1%) achieved pCR after NAC. Multivariate analysis identified five independent predictive factors for pCR: Lauren intestinal type [odds ratio (OR) = 3.28], lower clinical T stage (OR = 2.75), CEA decrease ≥ 70% after NAC (OR = 3.42), pre-treatment NLR < 2.5 (OR = 2.13), and ≥ 4 chemotherapy cycles (OR = 2.87). The fluorouracil, leucovorin, oxaliplatin, docetaxel regimen achieved the highest pCR rate (27.5%), and oxaliplatin-containing regimens were superior to cisplatin-containing regimens (22.3% vs 12.7%, P = 0.034). Patients with both low NLR and platelet-to-lymphocyte ratio had the highest pCR rate (33.8%), while those with both high inflammatory markers had the lowest rate (10.7%). Earlier clinical stage disease (cT3N+ vs cT4N+: 28.6% vs 13.0%) and lower lymph node burden were associated with higher pCR rates.

CONCLUSION

The achievement of pCR after NAC in gastric cancer patients is closely associated with Lauren intestinal type, lower clinical T stage, a significant decrease in CEA after chemotherapy, low pre-treatment NLR, and an adequate number of chemotherapy cycles.

Keywords: Gastric cancer; Neoadjuvant chemotherapy; Pathological complete response; Predictive factor

Core Tip: This study included patients with pathologically confirmed gastric adenocarcinoma who received neoadjuvant chemotherapy and completed radical gastrectomy + D2 dissection. Unified tumor regression grade assessment defines pathological complete response as the absence of residual primary tumor and lymph node metastasis. The system collected demographic data, comorbidities, tumor location and clinical stage, Lauren classification, human epidermal growth factor receptor 2/microsatellite instability/programmed death-ligand 1, baseline and dynamic laboratory indicators imaging and endoscopic responses, chemotherapy regimens/cycles/dose intensities and adverse reactions. With pathological complete responses the primary outcome, univariate and multivariate logistic regression were used to screen independent predictors.