Not all major pathological responses are equal: prognostic heterogeneity and risk stratification after neoadjuvant chemoimmunotherapy in resectable NSCLC.
- 1Department of Thoracic Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
- 2Shantou University Medical College, Shantou, China.
- 3Department of Thoracic Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
Abstract
Background
Major pathological response (MPR) is a widely used efficacy endpoint for neoadjuvant chemoimmunotherapy (NCIT) in resectable non-small cell lung cancer (NSCLC). However, whether MPR without pathological complete response (pCR) represents a prognostically homogeneous population remains unclear, and optimal postoperative management strategies require further exploration. This study evaluated the prognostic heterogeneity, risk stratification, and recurrence patterns of patients achieving MPR.Methods
This dual-center, retrospective cohort study included 588 patients with resectable NSCLC who received NCIT followed by radical surgery. The primary endpoint was recurrence-free survival (RFS). Patients were categorized into mutually exclusive pCR (n=200), non-pCR MPR (≤10% residual viable tumor without pCR; n = 111), and Non-MPR (n=277) groups. Kaplan-Meier curves and multivariable Cox proportional hazards regression were used to evaluate prognostic factors and develop a risk-stratification system within the MPR subgroup. Additionally, the effect of postoperative adjuvant therapy was evaluated via exploratory subgroup analyses, and anatomical recurrence patterns were systematically compared across response groups.Results
Recurrence-free survival (RFS) differed among the three groups, with MPR representing an intermediate-risk state. Within the MPR subgroup, baseline cT3-4 stage, postoperative ypN positivity, and lower harvested lymph node count were independently associated with RFS. A simplified system effectively divided MPR patients into low-risk (RFS comparable to pCR) and high-risk groups (RFS approaching Non-MPR). Adjuvant therapy showed no statistically significant RFS benefit in pathological response subgroups. Furthermore, recurrence patterns did not significantly differ among response groups, with brain and bone remaining the predominant distant metastatic sites.Conclusions
Non-pCR MPR after NCIT is a prognostically heterogeneous state in NSCLC. Stratifying these patients using baseline cT stage, ypN status, and lymph node count refines postoperative risk assessment, highlighting the continued necessity of thorough lymph node dissection. Although adjuvant therapy did not show a definitive RFS benefit in our cohort, its potential value, especially in high-risk MPR patients, warrants prospective validation and should not be interpreted as evidence of lack of benefit. Furthermore, the observed recurrence patterns across response groups, with brain and bone being frequently observed metastatic sites, provide preliminary insights into metastatic distribution after NCIT and may serve as a reference for future surveillance studies.
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BibTeX
@article{lin2026major,
title = {{Not all major pathological responses are equal: prognostic heterogeneity and risk stratification after neoadjuvant chemoimmunotherapy in resectable NSCLC.}},
author = {Jiong Lin and Haijie Xu and Jiming Tang and Chaoquan He and Peishen Li and Xirui Lin and Jiaying Wu and Zexin Huang and Chenshu Huang and Zefeng Xie and Hansheng Wu},
journal = {Frontiers in immunology},
year = {2026},
month = sep,
doi = {10.3389/fimmu.2026.1925301},
url = {https://europepmc.org/article/MED/42857111},
note = {CC BY},
}
RIS
TY - JOUR
TI - Not all major pathological responses are equal: prognostic heterogeneity and risk stratification after neoadjuvant chemoimmunotherapy in resectable NSCLC.
AU - Jiong Lin
AU - Haijie Xu
AU - Jiming Tang
AU - Chaoquan He
AU - Peishen Li
AU - Xirui Lin
AU - Jiaying Wu
AU - Zexin Huang
AU - Chenshu Huang
AU - Zefeng Xie
AU - Hansheng Wu
PY - 2026
DA - 2026/09/25
JO - Frontiers in immunology
DO - 10.3389/fimmu.2026.1925301
UR - https://europepmc.org/article/MED/42857111
AB - Background Major pathological response (MPR) is a widely used efficacy endpoint for neoadjuvant chemoimmunotherapy (NCIT) in resectable non-small cell lung cancer (NSCLC). However, whether MPR without pathological complete response (pCR) represents a prognostically homogeneous population remains unclear, and optimal postoperative management strategies require further exploration. This study evaluated the prognostic heterogeneity, risk stratification, and recurrence patterns of patients achieving MPR.Methods This dual-center, retrospective cohort study included 588 patients with resectable NSCLC who received NCIT followed by radical surgery. The primary endpoint was recurrence-free survival (RFS). Patients were categorized into mutually exclusive pCR (n=200), non-pCR MPR (≤10% residual viable tumor without pCR; n = 111), and Non-MPR (n=277) groups. Kaplan-Meier curves and multivariable Cox proportional hazards regression were used to evaluate prognostic factors and develop a risk-stratification system within the MPR subgroup. Additionally, the effect of postoperative adjuvant therapy was evaluated via exploratory subgroup analyses, and anatomical recurrence patterns were systematically compared across response groups.Results Recurrence-free survival (RFS) differed among the three groups, with MPR representing an intermediate-risk state. Within the MPR subgroup, baseline cT3-4 stage, postoperative ypN positivity, and lower harvested lymph node count were independently associated with RFS. A simplified system effectively divided MPR patients into low-risk (RFS comparable to pCR) and high-risk groups (RFS approaching Non-MPR). Adjuvant therapy showed no statistically significant RFS benefit in pathological response subgroups. Furthermore, recurrence patterns did not significantly differ among response groups, with brain and bone remaining the predominant distant metastatic sites.Conclusions Non-pCR MPR after NCIT is a prognostically heterogeneous state in NSCLC. Stratifying these patients using baseline cT stage, ypN status, and lymph node count refines postoperative risk assessment, highlighting the continued necessity of thorough lymph node dissection. Although adjuvant therapy did not show a definitive RFS benefit in our cohort, its potential value, especially in high-risk MPR patients, warrants prospective validation and should not be interpreted as evidence of lack of benefit. Furthermore, the observed recurrence patterns across response groups, with brain and bone being frequently observed metastatic sites, provide preliminary insights into metastatic distribution after NCIT and may serve as a reference for future surveillance studies.
SN - 1664-3224
ER -