Baseline Inflammatory and Nutritional Indices Show Limited Discrimination for Major Pathological Response and Survival After Neoadjuvant Chemotherapy for Gastric Cancer: A Retrospective Comparison of Eleven Indices

Background/Objectives: While perioperative chemotherapy is standard for locally advanced gastric cancer, no baseline blood marker reliably identifies which patients will respond to treatment. In this retrospective study, we compared eleven inflammatory and nutritional indices against pathological response and survival using data collected between 2020 and 2025. Methods: We analyzed 130 patients with gastric adenocarcinoma receiving perioperative systemic therapy at two centers. Eleven indices—the neutrophil-to-lymphocyte ratio (NLR), systemic immune–inflammation index (SII), Prognostic Nutritional Index (PNI), and eight further indices defined—were assessed against the Mandard tumor regression grade (TRG), overall survival (OS), and disease-free survival (DFS). Results: The median age was 63 years, and the median follow-up was 22.1 months from diagnosis. A Mandard TRG was assigned in 123 patients, 32 of whom achieved a major pathological response (TRG 1–2). The PNI had the highest point estimate of discrimination for major pathological response (AUC 0.618, 95% CI 0.490–0.746; p = 0.070), but its area under the curve did not differ significantly from that of any other index (all p ≥ 0.18), and bootstrap validation incorporating index selection and threshold derivation yielded an optimism-corrected AUC of 0.567. While PNI ≥ 53 was nominally associated with TRG 1–2 (OR 3.823, 95% CI 1.503–9.722; p = 0.005), no association survived correction for multiple comparisons, and the PNI was selected as the best-performing index in only 49% of bootstrap resamples. No index showed a statistically significant association with overall survival, and the event count is insufficient to establish the presence or absence of an association. Conclusions: None of the eleven baseline blood-based indices demonstrated statistically robust or clinically useful discrimination for major pathological response, and none were associated with survival. Although the PNI represented the most promising exploratory signal, its apparent advantage was not statistically distinguishable from the other indices and did not survive internal validation. The threshold of approximately 53 should be regarded as hypothesis-generating only.