Association of Adjuvant Chemotherapy With Overall Survival Among Patients With Locally Advanced Gastric Cancer After Neoadjuvant Chemotherapy

This cohort study compares survival among patients with locally advanced gastric cancer who did and did not receive adjuvant chemotherapy after neoadjuvant chemotherapy followed by surgery. Importance Neoadjuvant chemotherapy (NAC) is a standard treatment option for locally advanced gastric cancer (LAGC); however, the indications for adjuvant chemotherapy (AC) in patients with LAGC who received NAC remain controversial. Objective To compare survival rates between patients with LAGC who received AC and those who did not after NAC followed by surgery. Design, Setting, and Participants This multicenter, international cohort study included 353 patients with LAGC undergoing curative-intent gastrectomy after NAC at 2 tertiary referral teaching hospitals in China between June 1, 2008, and December 31, 2017. To externally validate the findings in the Chinese patients, 109 patients from the US and Italy between June 1, 2006, and June 30, 2013, were reviewed. The follow-up period of the Chinese patients was completed in December 2020, and the follow-up period of the Western patients was completed between February and July 2017. Data analysis was performed from December 1, 2020, to February 28, 2021. Exposures Patients who received AC and those who did not were propensity score matched to evaluate the association of AC with survival. Main Outcomes and Measures Overall survival (OS), disease-free survival, and disease-specific survival. Results Of 353 patients from China (275 [78.1%] male; mean [SD] age, 58.0 [10.7] years), 262 (74.1%) received AC and 91 (25.9%) did not. After propensity score matching, the 3-year OS was significantly higher in patients who received AC (60.1%; 95% CI, 53.1%-68.1%) than in those who did not (49.3%; 95% CI, 39.8%-61.0%) (P = .02). Lymph node ratio (LNR) was significantly associated with AC benefit (P < .001 for interaction), and a plot of the interaction between LNR and AC demonstrated that AC was associated with improved OS in patients with higher (>= 9%) LNRs (3-year OS: 46.6% vs 21.7%; P < .001), but not in patients with LNRs less than 9% (3-year OS: 73.9% vs 71.3%; P = .30). When stratified by AC cycles, only those patients who completed at least 4 AC cycles exhibited a significant survival benefit in the 6-month (hazard ratio, 0.56; 95% CI, 0.33-0.96; P = .03) and 9-month landmark analysis (hazard ratio, 0.50; 95% CI, 0.27-0.94; P = .03). In the external cohort, improved OS with AC administration was also found in patients with LNRs of 9% or greater (3-year OS: 53.0% vs 26.3%; P = .04). Conclusions and Relevance In this cohort study, the administration of AC after NAC and resection of LAGC was associated with improved prognosis in patients with LNRs of 9% or greater. These findings suggest that LNR might be valuable in AC selection in future decision-making processes. Question Is adjuvant chemotherapy associated with a survival benefit for patients with locally advanced gastric cancer who underwent curative-intent gastrectomy after neoadjuvant chemotherapy? Findings In this cohort study of 462 patients with locally advanced gastric cancer from Western and Eastern countries, adjuvant chemotherapy was associated with significantly improved survival in patients with a lymph node ratio of at least 9% compared with those who did not receive adjuvant chemotherapy. Meaning These findings suggest that the lymph node ratio could be useful in adjuvant chemotherapy selection for locally advanced gastric cancer after neoadjuvant chemotherapy in future decision-making processes.