Molecular profiling-directed individualized adjuvant therapy in colorectal cancer: Bridging consensus guidelines to clinical disparities

Table 2 Key technical parameters for circulating tumor DNA-based minimal residual disease detection in colorectal cancer

Parameter	Common options/considerations	Clinical implications and challenges
Assay technology	Tumor-informed (PCR-based, NGS); tumor-agnostic (methylation-based, fixed-panel NGS)	Tumor-informed: Higher sensitivity, requires tumor tissue. Tumor-agnostic: Faster turnaround, may have lower sensitivity. Choice impacts cost and logistics
Optimal timing window	Post-operative baseline: 4-6 weeks after surgery; adjuvant therapy monitoring: Every 3-6 months during treatment; surveillance: Every 3-6 months for up to 2-3 years	No universally standardized timeline. Early testing (2-4 weeks) may detect surgical shedding, while testing too late may miss early recurrence
Positivity threshold	Varies by assay (e.g., MTMLD: 0.01%-0.02%; fixed-panel NGS: Often 0.1% VAF). Often defined as ≥ 2 unique tumor-derived fragments	Lack of uniformity leads to results not being directly comparable across different platforms and laboratories
Key performance metrics	Sensitivity: 70%-95% (depends on assay and tumor shed); specificity: > 99%. Lead time: Median 8-9 months ahead of radiographic recurrence	High specificity ensures ctDNA-positivity is highly actionable. Sensitivity limitations mean a negative result cannot fully rule out MRD

PCR: Polymerase chain reaction; NGS: Next-generation sequencing; MTMLD: Multiplex polymerase chain reaction-based targeted deep sequencing; VAF: Variant allele frequency; ctDNA: Circulating tumor DNA; MRD: Minimal residual disease.