Post-operative MRD status more prognostic than TNM stage

Post-operative, circulating tumour (ct)DNA-based molecular residual disease (MRD) status is highly prognostic and outperforms the prognostic value of TNM staging in patients with colon adenocarcinoma, results from a retrospective analysis of clinical data of more than 3,000 patients demonstrated.

Currently, the prognosis and treatment plan for patients with colon adenocarcinoma is primarily dictated by AJCCs TNM staging, which includes tumour extent (T), lymph node involvement (N), and distant metastases (M). However, TNM status does not accurately predict disease-free survival (DFS) and/or the benefit of treatment.

Recent studies have highlighted the prognostic and predictive value of ctDNA-based detection of MRD after surgery [1]. Therefore, a study was performed to incorporate post-operative ctDNA results into the staging of colon adenocarcinoma. Dr Arvind Dasari (MD Anderson Cancer Center, TX, USA) presented the results [2].

The study retrospectively analysed clinical data of 3,148 patients with TNM stage I–III colon adenocarcinoma from 3 cohorts with available post-operative MRD results: GALAXY trial (UMIN000039205; n=2,170), BESPOKE CRC trial (NCT04264702; n=635), and real-world testing (n=343). Overall, 48% of the evaluated participants had stage III, 38% had stage II, and 14% had stage I colon adenocarcinoma. Adjuvant treatment and subsequent surveillance were per standard guidelines. DFS was determined as time from surgery to tumour recurrence, second primary tumour, or death. The median follow-up ranged from 22 to 32 months.

ctDNA-based MRD status was assessed at 2–10 weeks post-resection. MRD-positivity was observed in 13% of the participants and correlated with pathological stage (stage I: 1%, stage II: 7%, and stage III: 20%). In participants with TNM stage II and stage III, MRD-positivity was significantly correlated with poor prognosis, with 24-month DFS having a hazard ratio of up to 28 for the comparison of MRD-negative versus MRD-positive participants.

MRD status was more prognostic for DFS than pathological TNM stage. For example, 24-month DFS rate in MRD-positive participants with stage IIA disease was 35.1%, while it was 80.1% in MRD-negative participants with stage IIIC disease (see Table). Regardless of the TNM stage, most participants with MRD-positivity are expected to have disease recurrence within 2 years.

Table: MRD status is associated with 24-month DFS [2]



N/A, not available

“This data strongly suggests that the addition of post-operative, ctDNA-based MRD status to TNM staging can better risk-stratify patients with colon adenocarcinoma,” Dr Dasari concluded. Longer follow-up is needed to further validate these results.

1. Dasari A, et al. Nat Rev Clin Oncol. 2020;17:757-770.
2. Dasari A, et al. Is it time for a new staging system for colon adenocarcinoma? Abstract 4MO, ESMO Gastrointestinal Cancers Congress 2024, 26–29 June, Munich, Germany.

Copyright ©2024 Medicom Medical Publishers



Posted on 21 August 202421 August 2024