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Background <p>Immune checkpoint inhibitors improve survival in advanced esophageal squamous cell carcinoma (ESCC), yet many patients derive limited benefit, and identifying those at high risk of poor outcomes remains challenging. Most immune-nutritional composite scores use only pre-treatment data and have rarely been applied to on-treatment risk monitoring. We developed and internally validated the Prealbumin–Immune-Inflammation–Neutrophil-to-Lymphocyte Ratio Prognostic Score (PINPS) and explored a four-quadrant dynamic framework integrating baseline risk with early post-treatment change.</p> Methods <p>This single-centre retrospective study enrolled 549 consecutive ESCC patients treated with PD-1/PD-L1 inhibitors between 2019 and 2026. After excluding 24 with incomplete follow-up, 525 were analysed for overall survival (OS). After multiple imputation (m = 20), 12 candidate markers and indices were screened using LASSO-penalised Cox regression with bootstrap internal validation. As a post hoc extension, patients were cross-classified by baseline PINPS risk (high/low) and change in the earliest post-treatment value obtained between days 21 and 90 (decrease/non-decrease). Cytokine correlations (<i>n</i> = 325) and exploratory TBNK immunophenotyping (<i>n</i> = 239) were assessed in available subsets.</p> Results <p>During a median follow-up of 10.7 months, 150 deaths occurred. PINPS retained three routine blood-based components: prealbumin, pan-immune-inflammation value, and neutrophil-to-lymphocyte ratio. Its bootstrap-corrected C-index was 0.667 (95% CI 0.615–0.719), improving by 0.145 over clinical variables alone (<i>P</i> &lt; 0.0001). Although continuous ΔPINPS magnitude was not associated with survival (<i>P</i> = 0.864), the four-quadrant framework discriminated OS in landmark analysis (<i>P</i> = 0.0032). Median survival was 18.3 versus 36.8 months in the persistent-high-risk versus baseline-low/decreasing-PINPS groups. Among baseline high-risk patients, 37.7% were reclassified as low risk during treatment. IL-6 was the only cytokine correlated with both baseline PINPS and early PINPS change (all FDR &lt; 0.05), while exploratory TBNK analysis suggested T-cell polarisation.</p> Conclusions <p>PINPS provides clinically interpretable survival stratification for ESCC patients receiving PD-1/PD-L1 inhibitors. Its post hoc four-quadrant framework identified a persistent-high-risk subgroup with the worst prognosis and suggested on-treatment risk reclassification in over one-third of baseline high-risk patients. External validation is required before clinical use.</p>

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Development and internal validation of a dynamic Prealbumin–Immune-Inflammation–NLR Prognostic Score (PINPS) for esophageal squamous cell carcinoma treated with immune checkpoint inhibitors: a retrospective cohort study

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  • 发表日期：

    2026年7月15日

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  • Huiping Ding,
  • Shengnan Hao,
  • Gengsheng He,
  • Kuaile Zhao,
  • Yiqun Ling

摘要

Background

Immune checkpoint inhibitors improve survival in advanced esophageal squamous cell carcinoma (ESCC), yet many patients derive limited benefit, and identifying those at high risk of poor outcomes remains challenging. Most immune-nutritional composite scores use only pre-treatment data and have rarely been applied to on-treatment risk monitoring. We developed and internally validated the Prealbumin–Immune-Inflammation–Neutrophil-to-Lymphocyte Ratio Prognostic Score (PINPS) and explored a four-quadrant dynamic framework integrating baseline risk with early post-treatment change.

Methods

This single-centre retrospective study enrolled 549 consecutive ESCC patients treated with PD-1/PD-L1 inhibitors between 2019 and 2026. After excluding 24 with incomplete follow-up, 525 were analysed for overall survival (OS). After multiple imputation (m = 20), 12 candidate markers and indices were screened using LASSO-penalised Cox regression with bootstrap internal validation. As a post hoc extension, patients were cross-classified by baseline PINPS risk (high/low) and change in the earliest post-treatment value obtained between days 21 and 90 (decrease/non-decrease). Cytokine correlations (n = 325) and exploratory TBNK immunophenotyping (n = 239) were assessed in available subsets.

Results

During a median follow-up of 10.7 months, 150 deaths occurred. PINPS retained three routine blood-based components: prealbumin, pan-immune-inflammation value, and neutrophil-to-lymphocyte ratio. Its bootstrap-corrected C-index was 0.667 (95% CI 0.615–0.719), improving by 0.145 over clinical variables alone (P < 0.0001). Although continuous ΔPINPS magnitude was not associated with survival (P = 0.864), the four-quadrant framework discriminated OS in landmark analysis (P = 0.0032). Median survival was 18.3 versus 36.8 months in the persistent-high-risk versus baseline-low/decreasing-PINPS groups. Among baseline high-risk patients, 37.7% were reclassified as low risk during treatment. IL-6 was the only cytokine correlated with both baseline PINPS and early PINPS change (all FDR < 0.05), while exploratory TBNK analysis suggested T-cell polarisation.

Conclusions

PINPS provides clinically interpretable survival stratification for ESCC patients receiving PD-1/PD-L1 inhibitors. Its post hoc four-quadrant framework identified a persistent-high-risk subgroup with the worst prognosis and suggested on-treatment risk reclassification in over one-third of baseline high-risk patients. External validation is required before clinical use.