ctDNA-based molecular residual disease and survival in resectable colorectal cancer.
Journal
Nature medicine
ISSN
1546-170X
Date Issued
2024-09-16
Author(s)
Nakamura, Yoshiaki
Watanabe, Jun
Akazawa, Naoya
Hirata, Keiji
Kataoka, Kozo
Yokota, Mitsuru
Kato, Kentaro
Kotaka, Masahito
Kagawa, Yoshinori
Mishima, Saori
Yukami, Hiroki
Ando, Koji
Miyo, Masaaki
Misumi, Toshihiro
Yamazaki, Kentaro
Ebi, Hiromichi
Okita, Kenji
Hamabe, Atsushi
Sokuoka, Hiroki
Kobayashi, Satoshi
Laliotis, George
Aushev, Vasily N
Sharma, Shruti
Jurdi, Adham
Liu, Minetta C
Aleshin, Alexey
Rabinowitz, Matthew
Bando, Hideaki
Taniguchi, Hiroya
Takemasa, Ichiro
Kato, Takeshi
Kotani, Daisuke
Mori, Masaki
Yoshino, Takayuki
Oki, Eiji
Abstract
The interim analysis of the CIRCULATE-Japan GALAXY observational study demonstrated the association of circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) detection with recurrence risk and benefit from adjuvant chemotherapy (ACT) in resectable colorectal cancer (CRC). This updated analysis with a 23-month median follow-up, including 2,240 patients with stage II-III colon cancer or stage IV CRC, reinforces the prognostic value of ctDNA positivity during the MRD window with significantly inferior disease-free survival (DFS; hazard ratio (HR): 11.99, P < 0.0001) and overall survival (OS; HR: 9.68, P < 0.0001). In patients who experienced recurrence, ctDNA positivity correlated with shorter OS (HR: 2.71, P < 0.0001). The significantly shorter DFS in MRD-positive patients was consistent across actionable biomarker subsets. Sustained ctDNA clearance in response to ACT was an indicator of favorable DFS and OS compared to transient clearance (24-month DFS: 89.0% versus 3.3%; 24-month OS: 100.0% versus 82.3%). True spontaneous clearance rate with no clinical recurrence was 1.9% (2/105). Overall, our findings provide evidence for the utility of ctDNA monitoring for post-resection recurrence and mortality risk stratification that could be used for guiding adjuvant therapy.
SDGs
Type
journal article