Liquid Biopsy-Based Novel Modality for Postoperative Management of Lung Cancer

Approximately 30% of early-stage lung cancer patients experience recurrence after curative surgery. However, the clinical utility of routine chest CT surveillance remains limited. Emerging evidence has demonstrated that liquid biopsy-based minimal residual disease (MRD) detection may serve as a more sensitive monitoring strategy. Longitudinal ctDNA dynamics analysis further enables real-time assessment of tumor progression and early detection of molecular relapse.

This study aims to develop a novel multidimensional approach for non-invasive postoperative recurrence monitoring in lung cancer and establish an MRD-guided adjuvant therapy model to optimize precision treatment and MRD-stratified follow-up protocols for lung cancer patients. This study will evaluate the sensitivity and specificity of novel monitoring methods and further compare emerging non-invasive recurrence monitoring approaches with conventional ctDNA-based techniques, driving continuous advancements in lung cancer research.

• Adaptive postoperative management based on minimal residual disease (Other): participants will not receive postoperative treatment if (neoadjuvant therapy efficacy reaches pCR and) MRD results keep negative.

Primary outcomes

• Two-year recurrence-free survival rate [Time from curative surgery to confirmation of clinical progression (recurrence or metastasis) within two years.]: The difference in the proportion of patients with (suspected) relapse or metastasis between the intervention group and the control group within two years.

Secondary outcomes

• Overall survival [Time from curative surgery to confirmation of death (any cause)，assessed up to 60 months.]: The difference in overall survival between the intervention group and the control group.
• Incremental cost effectiveness ratio [24 months after surgery]: The cost of lung cancer-related treatment, including the cost of drugs, follow-up treatment, drug management costs (consultation fees, anti-tumor drug allocation fees, intravenous infusion fees, nursing fees, etc.), follow-up costs, laboratory tests and imaging examination costs, and the management costs of adverse reactions (1 cycle is counted as 1 time), and the per capita standard expenses calculated according to the Checkmate816 study protocol and China's expenses were used to calculate ICER.
• Timely diagnosis rate by the novel MRD monitoring technique [two years]: The proportion of patients with recurrence signals detected by non-invasive methods prior to clinical confirmation of recurrence/metastasis, and quantify the mean lead time.
• Sensitivity of the novel MRD monitoring approach [two years]: Evaluate the sensitivity of the novel MRD-based assay against previous ctDNA-MRD-only approaches. Use receiver operating characteristic (ROC) curves and limit of detection (LoD) analyses for cross-platform comparison.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Non-small cell lung cancer with stage IA-IIIA (8th edition TNM classification) planning to undergo curative surgery or to undergo neoadjuvant therapy
* Solid nodules >1 cm or ground-glass nodules >1.5 cm on imaging
* No history of malignancies other than non-small cell lung cancer in the past 5 years
* Specimens are well preserved and imaging documents are accessible.

Exclusion Criteria:

* Age<18 years old
* Non-small cell lung cancer with pathologic stage IIIB-IV (8th edition TNM classification)
* Pathology results confirmed not to be non-small cell lung cancer
* History of malignancies other than non-small cell lung cancer in the past 5 years

• Kezhong Chen, MD, Study chair, Peking University People's Hospital
• Guangxi Wang, PhD, Study director, Peking University
• Jiatao Zhang, MD, Study director, Guangdong Provincial People's Hospital
• Rong Yin, MD, Study director, Jiangsu Cancer Institute & Hospital
• Ziming Li, MD, Study director, Shanghai Chest Hospital
• Yintao Li, MD, Principal investigator, Shandong Cancer Hospital and Institute
• Zizi Zhou, MD, Principal investigator, Shenzhen Third People's Hospital
• Fang Wu, MD, Principal investigator, Second Xiangya Hospital of Central South University
• Jun Yin, MD, Principal investigator, Shanghai Zhongshan Hospital
• Yuan Cheng, MD, Principal investigator, Peking University First Hospital
• Quanfu Huang, MD, Principal investigator, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
• Xiaojun Zhu, PhD, Principal investigator, China National Institute for Occupational Safety and Health (NIOSH/CDC)