Research investigating the potential impact of postoperative adjuvant chemotherapy cycles on patients with lymph node-negative gastric cancer following neoadjuvant chemotherapy is currently sparse. This study aims to explore the effect of adjuvant chemotherapy cycles on the prognosis of this specific patient group.

We analyzed clinicopathological data from patients at four institutions between 2010 and 2020. Independent risk factors associated with 3-year overall survival (OS) were identified using a Cox proportional hazards regression model.

We enrolled a total of 219 patients in this study. Patients with lymph node-negative gastric cancer who received neoadjuvant chemotherapy and underwent at least five cycles of adjuvant chemotherapy (AC ≥ 5) after surgery had a significantly higher 3-year overall survival rate of 86.8% compared with those who received fewer than five cycles (AC < 5) with a survival rate of 68.1% (P = 0.016). Multivariate analysis identified several factors, including AC ≥ 5 (HR 0.367, 95% CI 0.166–0.815, P = 0.014), ypT stage ≥ 2 (HR 2.779, 95% CI 1.199–6.438, P = 0.017), and poorly differentiated tumors (HR 2.501, 95% CI 1.385–4.517, P = 0.002), as independently associated with 3-year OS in this patient group. Stratified analysis further revealed that AC ≥ 5 significantly enhanced long-term outcomes in patients with ypT stage ≥2 (3-year OS, 82.5% vs. 62.6%, P = 0.025) and in those with poorly differentiated tumors (3-year OS, 82.6% vs. 53.3%, P = 0.021).

Patients who have lymph node-negative gastric cancer following neoadjuvant chemotherapy, with either ypT stage ≥ 2 or poorly differentiated gastric cancers, may experience benefits from undergoing at least five cycles of adjuvant chemotherapy.