Postoperative ctDNA predicts survival in colorectal cancer

Postoperative circulating tumour DNA (ctDNA) has strong prognostic value for disease-free survival at 24 months, in patients with resectable colorectal cancer (CRC). In addition, in the GALAXY trial, postoperative ctDNA-positive patients, but not ctDNA-negative patients, derived a benefit from adjuvant treatment.

With the current standard-of-care treatment, more than 30% of patients with resectable CRC relapse. Postoperative ctDNA analysis may enable the identification of molecular residual disease and thus drive subsequent risk stratification and adjuvant chemotherapy treatment decision-making. Preliminary results from the prospective, observational GALAXY study (UMIN000039205) previously demonstrated that postsurgical ctDNA positivity (at 4 weeks after surgery) was associated with higher recurrence risk and was the most significant prognostic factor associated with recurrence risk in patients with stage II or IV CRC [1]. Dr Yoshiaki Nakamura (National Cancer Centre Hospital East, Japan) presented updated results of the GALAXY study [2].

In GALAXY, postoperative ctDNA status was determined at 1, 3, 6, 9, 12, 18, and 24 months after surgery until a recurrence in 2,625 participants with stages II–IV CRC. Participants with ctDNA-negativity at the 4-week timepoint demonstrated a significantly inferior disease-free survival at 24 months compared with ctDNA-positive participants: 89.0% versus 31.4% (HR 12.46; 95% CI 9.85–15.76; P<0.0001, see Figure).

Figure: CtDNA status linked to disease-free survival during the molecular residual disease window of 30 months [2]



In stage II–III participants who were negative for ctDNA-negative, postoperative, adjuvant chemotherapy did not improve disease-free survival at 24 months (88.3% vs 89.9%). On the contrary, in stage II–III ctDNA-positive participants, postoperative, adjuvant chemotherapy improved disease-free survival at 24 months (38.6% vs 16.1%).

Based on these results, Dr Nakamura concluded that “postoperative ctDNA has a strong prognostic value for disease-free survival at 24 months. In addition, postoperative ctDNA-positive participants, but not ctDNA-negative participants, derive benefit from adjuvant treatment.”

1. 
   
   1. Kotani D, et al. Nat Med. 2023;29:127–134.
   2. Nakamura Y, et al. Circulating tumor (ct)DNA as a prognostic biomarker in patients (pts) with resected colorectal cancer (CRC): An updated 24 months (mos) disease free survival (DFS) analysis from GALAXY study (CIRCULATE-Japan). Abstract 558MO, ESMO 2023, 20–24 October, Madrid, Spain.

Copyright ©2023 Medicom Medical Publishers



Posted on 18 December 202319 December 2023