Association of Recurrence-free Interval With Survival After Recurrence in Gastric Cancer: A Multicenter Retrospective Study
TL;DR
A longer log-transformed RFI was independently associated with higher mortality risk in patients receiving first-line chemotherapy for recurrent GC after gastrectomy, and the findings remained consistent after adjusting for treatment period, adjuvant chemotherapy, and first-line immune checkpoint inhibitor use.
Abstract
Background/Aim: The prognostic significance of recurrence-free interval (RFI) after gastrectomy in patients with gastric cancer (GC) remains unclear, and previous studies have reported inconsistent associations between the timing of recurrence and survival after recurrence. This study evaluated the association of RFI with post-recurrence overall survival (OS) and recurrence patterns in patients receiving first-line chemotherapy for recurrent GC. Patients and Methods: This multicenter retrospective study included 190 patients who underwent R0 gastrectomy and subsequently received first-line chemotherapy for recurrence between January 2015 and September 2025. RFI was analyzed as a log-transformed continuous variable and its association with post-recurrence OS was evaluated using multivariable Cox regression and restricted cubic spline models. Patients were classified into three groups according to RFI (<6, 6-12, and ≥12 months) for descriptive analyses of patient characteristics and recurrence patterns. Results: The prevalence of peritoneal recurrence increased across the three RFI groups (25.9%, 56.4%, and 56.5%, respectively; p=0.013). Multivariable analysis identified longer log-transformed RFI as independently associated with higher mortality risk [hazard ratio (HR)=1.42, 95% confidence interval (CI)=1.18-1.71; p<0.001]. Eastern Cooperative Oncology Group performance status ≥1 (HR=2.63, 95%CI=1.82-3.80; p<0.001), peritoneal recurrence (HR=2.06, 95%CI=1.45-2.91; p<0.001), and prognostic nutritional index (HR=0.95, 95%CI=0.92-0.98; p<0.001) were also independently associated with post-recurrence OS. There was a significant overall association between RFI and post-recurrence OS (p=0.0012), with no significant evidence of nonlinearity (p=0.18). The findings remained consistent after adjusting for treatment period, adjuvant chemotherapy, and first-line immune checkpoint inhibitor use. Conclusion: A longer log-transformed RFI was independently associated with higher mortality risk in patients receiving first-line chemotherapy for recurrent GC after gastrectomy. Prognostic assessment after recurrence should consider RFI together with performance status, nutritional status, and recurrence pattern.