Post-progression Nutritional and Immune Status Determines Survival After First-line Chemotherapy in Unresectable Advanced Gastric Cancer

Background/Aim: In unresectable advanced gastric cancer (AGC), overall survival (OS) is influenced more strongly by post-progression survival (PPS) than by progression-free survival (PFS). Although several determinants of PPS are known, the clinical significance of nutritional and immune status at the time of first disease progression remains unclear. We investigated the prognostic impact of the Prognostic Nutritional Index (PNI) at first progression on PPS after first-line chemotherapy for AGC. Patients and Methods: This retrospective single-center cohort study included 265 patients with unresectable recurrent or AGC who received first-line chemotherapy (January 2011-December 2016). PPS was defined as the interval from the date of first documented cancer progression to death. The PNI was calculated as 10 × serum albumin (g/dl) + 0.005 × peripheral lymphocyte count (/μl). Patients were grouped by PNI <45 (n=184) or ≥45 (n=81), and PPS and OS compared. Independent PPS predictors were assessed using Cox proportional hazards models. Results: The PNI <45 group had worse Eastern Cooperative Oncology Group performance status (ECOG-PS), lower body mass index, fewer first-line chemotherapy cycles, a lower second-line therapy transition rate, and significantly shorter PPS (median 3.4 vs. 9.9 months; log-rank p<0.001). On multivariate analysis, ECOG-PS ≥1, type-4 macroscopic appearance, shorter PFS of first-line chemotherapy, no second-line therapy, and PNI <45 (hazard ratio=2.080, 95% confidence interval=1.568-2.759; p<0.001) independently predicted poor PPS. PPS correlated strongly with OS (Spearman’s ρ=0.84; p<0.001). Conclusion: PNI at first disease progression robustly and independently predicts PPS in unresectable AGC, highlighting the critical clinical relevance of host nutritional and immune status after disease progression.