Molecular residual disease-based novel modality of postoperative management for non-small-cell lung cancer (REMODEL): Protocol for a prospective multicenter study
Xiaoqiu Yuan, Ruoyi Jin, Yunchu Wei, Yue He, Lin Weng, Zifan Li, Jun Aiden Wang, Xinrui Li, Junnan Xu, Jian Bai, Yun Wang, Qingna Zhang, Na Zhou, Yanyan Hou, Guangxi Wang, Jiatao Zhang, Rong Yin, Ziming Li, Yun Li, Fan Yang, Jun Wang, Kezhong ChenAbstract
Background and Objectives
Circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) has been confirmed to predict postoperative recurrence of early-stage non-small-cell lung cancer (NSCLC), outperforming conventional imaging modalities by improving diagnostic efficiency and eliminating radiation-related risks. Integrating ctDNA with other liquid biopsy omics methods might further increase monitoring accuracy. In addition, patients with longitudinal undetectable MRD exhibit a favorable outcome and may be overtreated after radical surgery, while those traditionally not recommended for adjuvant treatment but with positive MRD may have not received appropriate disease management. This prospective real-world trial involving ten clinical centers across China aims to develop a multiomics noninvasive platform for recurrence prediction and to determine whether postoperative management guided by ctDNA is noninferior to standard care.
Methods
We will recruit pathologically confirmed TNM stage IA-IIIA (8 th edition) NSCLC patients who are undergoing radical resection. Eligible participants will be divided into a standard treatment group and a ctDNA-guided group depending on their preference. Patients treated with or without neoadjuvant therapy will be studied in parallel. In the ctDNA-guided group, adjuvant therapy can be avoided for patients whose MRD is undetected at 1 month after surgery, and an additional requirement is to achieve a major pathological response for patients receiving neoadjuvant therapy. Imaging and MRD monitoring will be performed every 3–6 months for 3 years of follow-up, and postoperative management will be determined by the MRD results at each time point. Adjuvant therapy will be stopped if the patient's MRD status is continuously negative; otherwise, a treatment plan will be initiated after discussion among a multidisciplinary team (MDT). The recruitment phase began in April 2025, and 916 patients will be enrolled.
Discussion
This prospective, multicenter, real-world study provides innovative techniques and is the first to confirm the instructive value of MRD for postoperative management of resectable NSCLC.