Baseline inflammatory and metabolic indicators associated with early PD-1 inhibitor resistance in advanced cervical cancer: a retrospective cohort study

Background Despite the clinical success of PD-1/PD-L1 inhibitors, resistance remains a major barrier to durable responses in advanced cervical cancer. Identifying readily available biomarkers predictive of immunotherapy resistance may improve treatment selection and patient outcomes. Methods This single-center retrospective cohort study included 140 patients with histologically confirmed advanced or recurrent cervical cancer who received at least two cycles of PD-1 inhibitor therapy. Clinical characteristics, laboratory indices—including neutrophil-to-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH)—and prior treatment history were analyzed. Resistance was defined as confirmed progressive disease (iCPD) according to iRECIST criteria. Logistic regression and receiver operating characteristic (ROC) analyses were performed to identify independent predictors and evaluate model performance. Results Of 140 patients, 68 (48.6%) developed PD-1 inhibitor resistance. Resistant cases exhibited significantly higher baseline NLR (4.09 ± 1.64 vs. 3.02 ± 1.28, p < 0.001), elevated LDH (264.4 ± 88.9 U/L vs. 216.8 ± 69.4 U/L, p = 0.003), and more frequent prior chemotherapy (67.6% vs. 47.2%, p = 0.018). In multivariable logistic regression analysis, baseline NLR (OR = 1.62, 95% CI 1.21–2.17, p = 0.002), LDH (OR = 1.05 per 10 U/L increase, 95% CI 1.01–1.09, p = 0.012), and prior chemotherapy (OR = 2.08, 95% CI 1.01–4.28, p = 0.047) were independently associated with early PD-1 inhibitor resistance. The combined model incorporating NLR, LDH, PD-L1 expression, and prior chemotherapy achieved an AUC of 0.842 (95% CI 0.773–0.911), outperforming individual parameters ( p < 0.05). Exploratory analysis showed that PD-1–based combination regimens achieved a disease control rate of 72.2% in previously resistant patients. Conclusion Systemic inflammatory and metabolic markers, together with clinical treatment history, can effectively predict PD-1 inhibitor resistance in advanced cervical cancer.

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Journal
Frontiers in Medicine
Published
2026-03-16
DOI
https://doi.org/10.3389/fmed.2026.1779898
Primary Topic
Endometrial and Cervical Cancer Treatments
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article
Field-Weighted Citation Impact
0.00

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article

Baseline inflammatory and metabolic indicators associated with early PD-1 inhibitor resistance in advanced cervical cancer: a retrospective cohort study

Zhao Xiaoyan, Mo Shijiao, Liu Xiaojuan, Zhou Xiaofan
Frontiers in Medicine
Endometrial and Cervical Cancer Treatments
article

Baseline inflammatory and metabolic indicators associated with early PD-1 inhibitor resistance in advanced cervical cancer: a retrospective cohort study

Zhao Xiaoyan, Mo Shijiao, Liu Xiaojuan, Zhou Xiaofan
article en

Abstract

Background Despite the clinical success of PD-1/PD-L1 inhibitors, resistance remains a major barrier to durable responses in advanced cervical cancer. Identifying readily available biomarkers predictive of immunotherapy resistance may improve treatment selection and patient outcomes. Methods This single-center retrospective cohort study included 140 patients with histologically confirmed advanced or recurrent cervical cancer who received at least two cycles of PD-1 inhibitor therapy. Clinical characteristics, laboratory indices—including neutrophil-to-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH)—and prior treatment history were analyzed. Resistance was defined as confirmed progressive disease (iCPD) according to iRECIST criteria. Logistic regression and receiver operating characteristic (ROC) analyses were performed to identify independent predictors and evaluate model performance. Results Of 140 patients, 68 (48.6%) developed PD-1 inhibitor resistance. Resistant cases exhibited significantly higher baseline NLR (4.09 ± 1.64 vs. 3.02 ± 1.28, p < 0.001), elevated LDH (264.4 ± 88.9 U/L vs. 216.8 ± 69.4 U/L, p = 0.003), and more frequent prior chemotherapy (67.6% vs. 47.2%, p = 0.018). In multivariable logistic regression analysis, baseline NLR (OR = 1.62, 95% CI 1.21–2.17, p = 0.002), LDH (OR = 1.05 per 10 U/L increase, 95% CI 1.01–1.09, p = 0.012), and prior chemotherapy (OR = 2.08, 95% CI 1.01–4.28, p = 0.047) were independently associated with early PD-1 inhibitor resistance. The combined model incorporating NLR, LDH, PD-L1 expression, and prior chemotherapy achieved an AUC of 0.842 (95% CI 0.773–0.911), outperforming individual parameters ( p < 0.05). Exploratory analysis showed that PD-1–based combination regimens achieved a disease control rate of 72.2% in previously resistant patients. Conclusion Systemic inflammatory and metabolic markers, together with clinical treatment history, can effectively predict PD-1 inhibitor resistance in advanced cervical cancer.

Frontiers in MedicineVol. 13
Hebei North University (CN), First Hospital of Shijiazhuang (CN), Maternal and Child Health Care Hospital of Bao'an (CN)
Health Commission of Hebei Province
Openalex Percentile: Top 19%
Endometrial and Cervical Cancer Treatments
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