Prognostic nutritional index is associated with severe postoperative complications after neoadjuvant immunochemotherapy for esophageal squamous cell carcinoma: a retrospective cohort study with threshold effect analysis

BACKGROUND: Neoadjuvant immunochemotherapy (nICT) followed by esophagectomy has become the standard treatment for locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, severe postoperative complications remain a significant clinical concern. The prognostic nutritional index (PNI), reflecting both nutritional and inflammatory status, may identify patients at elevated risk for complications. This study aimed to investigate the dose-response relationship between preoperative PNI and severe postoperative complications, identify potential thresholds for risk stratification, and explore heterogeneity by pathological response. METHODS: This retrospective cohort study included 134 consecutive patients with LA-ESCC who received nICT followed by radical esophagectomy. Preoperative PNI was calculated as serum albumin (g/L) + 5 × total lymphocyte count (×10⁹/L). The primary outcome was severe postoperative complications (SPCs). Multivariable logistic regression, restricted cubic spline analysis, threshold effect analysis, and subgroup analyses were performed to evaluate the independent association of PNI and explore nonlinear relationships. RESULTS: SPCs occurred in 29 patients (21.6%). Multivariable analysis demonstrated that preoperative PNI was independently associated with SPCs (adjusted OR from the primary parsimonious model = 0.86, 95%CI: 0.78-0.96, P = 0.006). When PNI was categorized into quartiles, compared with Q1, the adjusted ORs for Q2, Q3, and Q4 were 0.22 (95% CI: 0.06-0.75, P = 0.016), 0.11 (95% CI: 0.03-0.46, P = 0.003), and 0.29 (95% CI: 0.08-1.06, P = 0.061), respectively, with a significant trend across quartiles (P for trend = 0.016). Restricted cubic spline analysis revealed a nonlinear "L-shaped" relationship between PNI and SPCs (P for non-linearity = 0.045). Threshold effect analysis identified 50.00 as the inflection point: below this threshold, each unit increase in PNI was associated with a 25% reduction in SPC risk (OR = 0.75, 95% CI: 0.594-0.936, P = 0.011); above this threshold, no significant association was observed (OR = 1.09, 95% CI: 0.872-1.372, P = 0.438). Subgroup analysis revealed significant heterogeneity by pathological response (P for interaction = 0.011): the protective effect of higher PNI was pronounced in non-pCR patients (OR = 0.80, 95% CI: 0.69-0.92) but absent in patients achieving pCR (OR = 1.06, 95% CI: 0.88-1.28). CONCLUSIONS: Preoperative PNI is independently associated with severe postoperative complications in LA-ESCC patients receiving nICT, exhibiting a nonlinear "L-shaped" relationship with a threshold of 50.00. The observed interaction with pCR status is exploratory and hypothesis-generating. Future prospective studies are needed to confirm these findings before clinical implementation.