Patterns of Survival and Recurrence in Poor Responders to Neoadjuvant Therapy for Gastric Cancer: A Real-World Multicenter Study.

BACKGROUND

Neoadjuvant therapy (NAT) is increasingly used in locally advanced gastric cancer (LAGC), but a significant proportion of patients respond poorly, causing adverse outcomes. Few studies have specifically examined the prognosis of this subgroup. This study aimed to analyze survival and recurrence in poor responders to guide follow-up and treatment strategies.

METHODS

This multicenter retrospective study included patients with LAGC who received NAT. Tumor regression was graded following the Becker system, defining TRG 2-3 as poor response. Outcomes were assessed for overall survival (OS), recurrence-free survival (RFS), and recurrence patterns.

RESULTS

648 patients were included: 341 with TRG 2 and 307 with TRG 3. In the entire cohort, the 3-year OS and RFS were 54.6% and 55.2%, respectively. Recurrence occurred in 299 patients, with the following recurrence patterns: distant metastasis (26.1%, n = 78), peritoneal metastasis (21.1%, n = 63), locoregional recurrence (18.7%, n = 56), and multiple-site recurrence (18.4%, n = 55). Liver metastasis was significantly higher in the TRG 3 group than in the TRG 2 group (14.1% versus 5.3%, P = 0.010). ypN+ was the most significant independent risk factor for recurrence (OR = 2.73, 95% CI 1.83-4.08, P < 0.001); an increasing number of positive lymph nodes led to higher 3-year cumulative mortality in patients. Despite poor response to NAT, completing over four adjuvant chemotherapy cycles was associated with improved survival outcomes.

CONCLUSION

Poor NAT responders in LAGC have high recurrence rates, particularly in the first year post-surgery, with ypN+ status being the strongest predictor of recurrence. Completing over four cycles of AC was associated with survival improvement in this group.