Use of circulating tumor DNA analysis to predict recurrence and need for adjuvant chemotherapy in stage I-IV colorectal cancer.

person Li-Ren Li Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China info_outline Li-Ren Li, Wenhua Fan, Zhiyuan Xia, Rongrong Chen, Dagui Lin, Fang Li, Yang Zheng, Jiongyong Luo, Yuanyuan Xiong, Pengli Yu, Wei Gao, Yuhua Gong, Sen Zhang, Feiran Zhang

Authors person Li-Ren Li Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China info_outline Li-Ren Li, Wenhua Fan, Zhiyuan Xia, Rongrong Chen, Dagui Lin, Fang Li, Yang Zheng, Jiongyong Luo, Yuanyuan Xiong, Pengli Yu, Wei Gao, Yuhua Gong, Sen Zhang, Feiran Zhang Organizations Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China, Department of Colorectal & Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China, Geneplus-Beijing, Beijing, Beijing, China, Geneplus-Beijing, Beijing, China, Department of General Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, China Abstract Disclosures Research Funding Other Foundation Natural Science Foundation of China [grant numbers 81872267, 82172802], Natural Science Foundation of Guangdong Province, China [grant number 2018A030313542] Background: Circulating tumor DNA (ctDNA) has emerged as a biomarker that can define the risk of recurrence after curative-intent surgery for patients with colorectal cancer (CRC). However, beyond the predictive power of postoperative ctDNA detection, the efficacy and potential limitations of ctDNA detection urgently need to be fully elucidated in a large cohort of CRC. Methods: We enrolled 309 patients with stages Ⅰ to Ⅳ CRC who underwent definitive surgery. Tumor tissues from those patients were sequenced by a custom-designed next-generation sequencing (NGS) panel to identify somatic mutations, and plasma was analyzed using ctDNA-based molecular residual disease (MRD) assay which integrated tumor genotype–informed and tumor genotype–naïve ctDNA analysis. Results: ctDNA was detected after surgery in 5.4%, 13.8%, 15% and 30% of patients with stage Ⅰ, Ⅱ, Ⅲ and Ⅳ disease, respectively, and in 17.5% of all longitudinal samples. Detection of MRD after surgery and in serial plasma samples during follow-up were associated with shorter disease-free survival (DFS) (hazard ratio [HR], 13.17; P < 0.0001 and HR, 14.44; P < 0.0001, respectively) independent of tumor site, stage, and MSI status. Within the population, only 13 patients (6.6%) with longitudinal undetectable MRD recurred, resulting in a negative predictive value of 93.4%. Correspondingly, the positive predictive value of longitudinal detectable MRD was 79.6%, with a median lead time of 10.1 months. Further subgroup analyses revealed that adjuvant therapy did not confer a superior survival for patients with undetectable or detectable MRD. Moreover, lung-only and peritoneal metastases were less detectable by MRD. Conclusions: Postoperative ctDNA status is a strong predictor of recurrence independent of stage and MSI status. Longitudinal undetectable MRD could be used to define the potentially cured population in CRC patients undergoing curative-intent surgery.