Circulating Tumor DNA in Stage III Colorectal Cancer, beyond Minimal Residual Disease Detection, toward Assessment of Adjuvant Therapy Efficacy and Clinical Behavior of Recurrences

Abstract

Statement of translational relevanceSensitive methods for recurrence risk stratification, monitoring therapeutic efficacy, and early recurrence detection may have a major impact on treatment decisions and outcomes for stage III colorectal cancer patients. Circulating tumor DNA assessments performed postoperative, postadjuvant, and serially during surveillance all allowed stratification of patients into high and low risk groups. CtDNA detected recurrence with a significant leadtime compared to CT-imaging and ctDNA growth rates were prognostic of survival.Treatment of ctDNA positive patients with standard adjuvant therapy prevented recurrence in only 20% of patients. Accordingly, further studies exploring the optimal treatment for ctDNA positive patients are needed, as well as interventional studies assessing the clinical utility of ctDNA-based risk-stratification. A promising opportunity is risk-stratified allocation of surveillance resources, which may improve both the cost-effectiveness and the overall clinical outcome of surveillance. Finally, ctDNA growth rates may identify patients who could benefit from immediate therapeutic intervention compared to awaiting recurrence.Research.

In the literature: December 2021

“…Moreover, a 50-fold increase in relapse is shown for ctDNA-positive compared with ctDNA-negative patients directly after ACT. 1 This confirms previous publications by the same group and others on the high value of ctDNA to discriminate relapsing from non-relapsing patients in stage III colon cancer after surgery and after ACT. 2 , 3 The central finding and clinical added value of this elegant study is that, in an effort to increase the knowledge on the utility of ctDNA in the adjuvant setting, the authors analyze serial blood samples before, during and after ACT.…”

“…In an inspiring publication in Clinical Cancer Research , Henriksen et al. 1 show in a prospective multicenter homogeneous cohort of 168 stage III colon cancer patients that the risk of relapse after surgery is seven times higher for ctDNA-positive compared with ctDNA-negative patients. Moreover, a 50-fold increase in relapse is shown for ctDNA-positive compared with ctDNA-negative patients directly after ACT.…”

Machine learning guided signal enrichment for ultrasensitive plasma tumor burden monitoring

“…For example, MRD identified via bespoke panels in urothelial carcinoma is strongly prognostic of disease recurrence, though up to 40% of ctDNA-negative patients experienced relapse 19 . Similar ‘false negatives’ were seen in breast 5 and colorectal cancer 22–24 , suggesting that further improvement in sensitivity is needed.…”

Circulating tumor DNA for prognosis assessment and postoperative management after curative‐intent resection of colorectal liver metastases

“…Growth was extensive ranging from 25% to 143% per month. 29 Consequently, it most likely would be a benefit for the patients with indeterminate findings if the delay to intervention could be avoided or minimized. To address this, we explored if a ctDNA assessment already at the time of the indeterminate finding could identify the subset of patients who would later be diagnosed with There are several limitations to our study, including a limited sample size from a single hospital and the potential risk for false positive findings related to subset analyses.…”