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Background <p>The albumin-to-alkaline phosphatase ratio (AAPR) has been reported as a prognostic biomarker in several malignancies, but its clinical relevance in advanced non-small cell lung cancer (NSCLC) patients treated with anlotinib remains unclear. This study aimed to examine the association between baseline AAPR and overall survival (OS). </p> Methods <p>We retrospectively and consecutively enrolled patients with advanced NSCLC who received anlotinib at Zhongshan Hospital, Fudan University (from June 2018 to September 2023) and Zhongshan Hospital (Xiamen), Fudan University (from April 2019 to February 2025). Baseline AAPR was calculated as serum albumin divided by alkaline phosphatase. The primary endpoint was OS. Cox proportional hazards models, smooth curve fitting, and two-piecewise Cox regression were used to evaluate the association between AAPR and OS. Sensitivity analyses, including prespecified subgroup analyses and distribution checks, were performed to evaluate robustness.</p> Results <p>During follow-up, 52.5% of patients died. Higher AAPR was independently associated with longer OS in multivariable Cox regression (HR = 0.22, 95% CI 0.09–0.56, <i>p</i> = 0.0014). Median OS increased progressively across AAPR tertiles (10.18, 13.93, and 20.43&#xa0;months; log-rank <i>p</i> = 0.0010). Smooth curve fitting revealed a significant non-linear relationship (<i>p</i> = 0.008), with an inflection point at 0.2036: below this threshold, mortality risk decreased steeply, while above it the association remained protective but attenuated. Subgroup analyses confirmed consistency across demographic, clinical, and treatment categories. Distribution checks verified adequate data density below the threshold.</p> Conclusion <p>Baseline AAPR was independently and non-linearly associated with OS in advanced NSCLC patients treated with anlotinib. Patients with AAPR &lt; 0.2036 represent a subgroup with particularly poor prognosis, while increases above the threshold remained protective but conferred diminishing benefit.</p>

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Nonlinear association between baseline albumin-to-alkaline phosphatase ratio and overall survival in advanced NSCLC treated with anlotinib: a two-center retrospective cohort study

  • 期刊论文

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  • 发表日期：

    2026年7月19日

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  • Ning Zhang,
  • Zhenyang Lin,
  • Jinzhan Chen,
  • Xiong Xiao,
  • Jiaxin Liu,
  • Qingwei Zhang,
  • Jinxian Huang,
  • Hongni Jiang,
  • Jiefei Ma,
  • Congyi Xie

摘要

Background

The albumin-to-alkaline phosphatase ratio (AAPR) has been reported as a prognostic biomarker in several malignancies, but its clinical relevance in advanced non-small cell lung cancer (NSCLC) patients treated with anlotinib remains unclear. This study aimed to examine the association between baseline AAPR and overall survival (OS).

Methods

We retrospectively and consecutively enrolled patients with advanced NSCLC who received anlotinib at Zhongshan Hospital, Fudan University (from June 2018 to September 2023) and Zhongshan Hospital (Xiamen), Fudan University (from April 2019 to February 2025). Baseline AAPR was calculated as serum albumin divided by alkaline phosphatase. The primary endpoint was OS. Cox proportional hazards models, smooth curve fitting, and two-piecewise Cox regression were used to evaluate the association between AAPR and OS. Sensitivity analyses, including prespecified subgroup analyses and distribution checks, were performed to evaluate robustness.

Results

During follow-up, 52.5% of patients died. Higher AAPR was independently associated with longer OS in multivariable Cox regression (HR = 0.22, 95% CI 0.09–0.56, p = 0.0014). Median OS increased progressively across AAPR tertiles (10.18, 13.93, and 20.43 months; log-rank p = 0.0010). Smooth curve fitting revealed a significant non-linear relationship (p = 0.008), with an inflection point at 0.2036: below this threshold, mortality risk decreased steeply, while above it the association remained protective but attenuated. Subgroup analyses confirmed consistency across demographic, clinical, and treatment categories. Distribution checks verified adequate data density below the threshold.

Conclusion

Baseline AAPR was independently and non-linearly associated with OS in advanced NSCLC patients treated with anlotinib. Patients with AAPR < 0.2036 represent a subgroup with particularly poor prognosis, while increases above the threshold remained protective but conferred diminishing benefit.