Precision Perioperative Treatment for Resectable Non-Small Cell Lung Cancer: Current Status and Perspectives
7 affiliations
- 1Division of Hematology/Oncology, Department of Internal Medicine, University of California Comprehensive Cancer Center, Sacramento, CA 95817, USA
- 2Medical Service, Veterans Affairs Northern California Health Care System, Mather, CA 95655, USA
- 3Division of Thoracic Surgery, Department of Surgery, University of California Davis School of Medicine, Sacramento, CA 95817, USA
- 4Surgery Service, Veterans Affairs Northern California Health Care System, Mather, CA 95655, USA
- 5Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, University of California Davis School of Medicine, Sacramento, CA 95817, USA
- 6Department of Pathology & Laboratory Medicine, University of California Davis School of Medicine, Sacramento, CA 95817, USA
- 7Investigational Drugs Pharmacy Program, Veterans Affairs Northern California Health Care System, Mather, CA 95655, USA
Abstract
The treatment paradigm for resectable non-small cell lung cancer (NSCLC) continues to evolve toward precision perioperative strategies. Despite curative-intent surgery, disease recurrence remains common. Adjuvant tyrosine kinase inhibitors have substantially improved disease-free survival and, in selected populations, overall survival, particularly for patients with sensitizing EGFR mutations or ALK rearrangements. Targeted therapies for other actionable genomic alterations (AGAs), including RET fusions, remain investigational. Adequate tissue acquisition and comprehensive molecular profiling before treatment initiation are therefore essential for optimal treatment selection. For patients without sensitizing EGFR mutations or ALK rearrangements, neoadjuvant or perioperative PD-(L)1 blockade combined with platinum-based chemotherapy has become a standard of care for eligible patients with resectable stage II–III NSCLC, improving pathological response, event-free survival, and, in select trials, overall survival. Multidisciplinary reassessment of resectability following neoadjuvant treatment is particularly important for borderline-resectable disease. Patients subsequently deemed unresectable require individualized management, potentially including definitive chemoradiotherapy followed by consolidation immunotherapy. Although cross-trial comparisons suggest advantages of neoadjuvant chemoimmunotherapy over adjuvant-only immunotherapy, direct randomized comparisons are lacking. The incremental benefit of postoperative immunotherapy after neoadjuvant chemoimmunotherapy remains uncertain for selected patients. Future priorities include optimizing treatment sequencing, improving pathological complete response rates, refining radiographic and molecular response assessment, investigating resistance mechanisms, and integrating circulating tumor DNA-based minimal residual disease detection into individualized postoperative treatment. Whether surgery can be safely omitted in exceptional responders also warrants prospective investigation. Together, these advances support a biomarker-driven, response-adapted approach to precision perioperative NSCLC management.
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BibTeX
@article{isaacs2026precision,
title = {{Precision Perioperative Treatment for Resectable Non-Small Cell Lung Cancer: Current Status and Perspectives}},
author = {Dayna J. Isaacs and Cathleen J. Park and Linjun Zha and Ruqiang Liang and Luis A. Godoy and Nicholas S. Stollenwerk and Dongguang Wei and Kao Y. Chang and Prabhu Rajappa and Tianhong Li},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18213456},
url = {https://www.mdpi.com/2072-6694/18/21/3456},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Precision Perioperative Treatment for Resectable Non-Small Cell Lung Cancer: Current Status and Perspectives
AU - Dayna J. Isaacs
AU - Cathleen J. Park
AU - Linjun Zha
AU - Ruqiang Liang
AU - Luis A. Godoy
AU - Nicholas S. Stollenwerk
AU - Dongguang Wei
AU - Kao Y. Chang
AU - Prabhu Rajappa
AU - Tianhong Li
PY - 2026
DA - 2026/10/26
JO - Cancers
DO - 10.3390/cancers18213456
UR - https://www.mdpi.com/2072-6694/18/21/3456
AB - The treatment paradigm for resectable non-small cell lung cancer (NSCLC) continues to evolve toward precision perioperative strategies. Despite curative-intent surgery, disease recurrence remains common. Adjuvant tyrosine kinase inhibitors have substantially improved disease-free survival and, in selected populations, overall survival, particularly for patients with sensitizing EGFR mutations or ALK rearrangements. Targeted therapies for other actionable genomic alterations (AGAs), including RET fusions, remain investigational. Adequate tissue acquisition and comprehensive molecular profiling before treatment initiation are therefore essential for optimal treatment selection. For patients without sensitizing EGFR mutations or ALK rearrangements, neoadjuvant or perioperative PD-(L)1 blockade combined with platinum-based chemotherapy has become a standard of care for eligible patients with resectable stage II–III NSCLC, improving pathological response, event-free survival, and, in select trials, overall survival. Multidisciplinary reassessment of resectability following neoadjuvant treatment is particularly important for borderline-resectable disease. Patients subsequently deemed unresectable require individualized management, potentially including definitive chemoradiotherapy followed by consolidation immunotherapy. Although cross-trial comparisons suggest advantages of neoadjuvant chemoimmunotherapy over adjuvant-only immunotherapy, direct randomized comparisons are lacking. The incremental benefit of postoperative immunotherapy after neoadjuvant chemoimmunotherapy remains uncertain for selected patients. Future priorities include optimizing treatment sequencing, improving pathological complete response rates, refining radiographic and molecular response assessment, investigating resistance mechanisms, and integrating circulating tumor DNA-based minimal residual disease detection into individualized postoperative treatment. Whether surgery can be safely omitted in exceptional responders also warrants prospective investigation. Together, these advances support a biomarker-driven, response-adapted approach to precision perioperative NSCLC management.
SN - 2072-6694
ER -