Survival benefit of adjuvant chemotherapy based on molecular residual disease detection in resected colorectal liver metastases: subgroup analysis from CIRCULATE-Japan GALAXY

• Published in: Annals of oncology Vol. 35; no. 11; pp. 1015 - 1025
• Main Authors: Kataoka, K., Mori, K., Nakamura, Y., Watanabe, J., Akazawa, N., Hirata, K., Yokota, M., Kato, K., Kotaka, M., Yamazaki, K., Kagawa, Y., Mishima, S., Ando, K., Miyo, M., Yukami, H., Laliotis, G., Sharma, S., Palsuledesai, C.C., Rabinowitz, M., Jurdi, A., Liu, M.C., Aleshin, A., Kotani, D., Bando, H., Taniguchi, H., Takemasa, I., Kato, T., Yoshino, T., Oki, E.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.11.2024
• Subjects: adjuvant chemotherapy; circulating tumor DNA; colorectal liver metastases; disease-free survival; prognostic biomarker; adjuvant chemotherapy; colorectal liver metastases; prognostic biomarker; disease-free survival; circulating tumor DNA; Colorectal liver metastases
• ISSN: 0923-7534; 1569-8041; 1569-8041
• DOI: 10.1016/j.annonc.2024.08.2240

The prognostic role of circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) detection and its utility for postsurgical risk stratification has been reported in colorectal cancer. In this study, we explored the use of ctDNA-based MRD detection in patients with colorectal liver metastases (CLM), for whom the survival benefit of adjuvant chemotherapy (ACT) after surgical resection remains unclear. Patients with CLM without extrahepatic disease from the GALAXY study (UMIN000039205) were included. The disease-free survival (DFS) benefit of ACT was evaluated in MRD-positive and -negative groups after adjusting for age, gender, number, and size of liver metastases, RAS status, and previous history of oxaliplatin for primary cancer. ctDNA was detected using a personalized, tumor-informed 16-plex polymerase chain reaction-next-generation sequencing (mPCR-NGS) assay. ctDNA-based MRD status was evaluated 2-10 weeks after curative surgery, before the start of ACT. Among 6061 patients registered in GALAXY, 190 surgically resected CLM patients without any preoperative chemotherapy were included with a median follow-up of 24 months (1-48 months). ctDNA positivity in the MRD window was 32.1% (61/190). ACT was administered to 25.1% (48/190) of patients. In the MRD-positive group, 24-month DFS was higher for patients treated with ACT [33.3% versus not reached, adjusted hazard ratio (HR): 0.07, P < 0.0001]; whereas no benefit of ACT was seen in the MRD-negative group (24-month DFS: 72.3% versus 62.2%, adjusted HR: 0.68, P = 0.371). Multivariate analysis showed that the size of liver metastases (HR: 3.94, P = 0.031) was prognostic of DFS in the MRD-positive group. In the MRD-negative group, however, none of the clinicopathological factors were prognostic of DFS. Our data suggest that ACT may offer notable clinical benefits in MRD-positive patients with CLM. MRD status-based risk stratification could be potentially incorporated in future clinical trials for CLM. •Association between ACT benefit and MRD status was assessed in patients with surgically resected colorectal liver metastases.•In the MRD-positive group, the benefit of ACT in improving disease-free survival (DFS) was observed in multivariate analysis.•On the other hand, the benefit of ACT was limited in the MRD-negative group.