Can minimal residual disease (MRD) testing be done in an adult patient over 50 with a history of sigmoid adenocarcinoma after surgical resection?

MRD Testing After Sigmoid Adenocarcinoma Resection

Yes, minimal residual disease (MRD) testing can be performed after surgical resection of sigmoid adenocarcinoma using circulating tumor DNA (ctDNA) assays, and this testing has demonstrated strong prognostic value for predicting recurrence and guiding adjuvant therapy decisions.

Available Testing Methods

MRD detection in colorectal cancer utilizes ctDNA analysis through two primary approaches:

• Tumor-informed techniques require initial sequencing of the resected tumor tissue to identify patient-specific somatic mutations, followed by personalized plasma ctDNA assays targeting those specific alterations 1, 2
• Tumor-agnostic (plasma-only) approaches analyze ctDNA without prior tumor tissue profiling, integrating both genomic and epigenomic cancer signatures to detect MRD 1

Both methods have demonstrated clinical utility, though tumor-informed approaches show higher sensitivity (pooled HR 8.66 for recurrence) compared to tumor-agnostic methods (pooled HR 3.76) 2.

Prognostic Significance

Post-operative ctDNA positivity is a powerful independent predictor of recurrence:

• Patients with detectable ctDNA after curative-intent surgery have a 7.27-fold increased risk of recurrence compared to ctDNA-negative patients across all stages 2
• For stage I-III disease specifically, the hazard ratio increases to 8.14 for recurrence-free survival 2
• Post-adjuvant chemotherapy ctDNA positivity confers an even higher risk (HR 10.59) for recurrence 2
• In one plasma-only assay study, all 15 patients with detectable ctDNA at one month post-definitive therapy recurred, yielding 100% positive predictive value 1

Optimal Timing for Testing

Landmark timepoint assessment:

• Draw plasma approximately 1 month (median 31.5 days) after completion of definitive therapy (surgery alone or surgery plus adjuvant chemotherapy) 1
• This early post-treatment assessment provides critical prognostic information with 100% specificity for recurrence 1

Serial monitoring strategy:

• Incorporate longitudinal sampling every 3-4 months during the first 2 years post-surgery to improve sensitivity from 55.6% at single landmark timepoint to 69-91% with serial assessments 1, 2
• Serial testing captures patients who develop detectable ctDNA later in their disease course 1

Clinical Utility

MRD testing addresses critical clinical decisions:

• Risk stratification: Identifies high-risk patients who may benefit from adjuvant chemotherapy despite favorable pathologic staging 2, 3
• Treatment monitoring: Assesses response to adjuvant therapy in real-time, potentially serving as a surrogate endpoint for treatment efficacy 2
• Recurrence prediction: Detects molecular recurrence months before radiographic or clinical evidence of disease 1, 4
• Actionable alterations: Tissue comprehensive genomic profiling can simultaneously identify targetable mutations in 54% of patients while enabling personalized MRD tracking 3

Performance Characteristics

The sensitivity and specificity vary by approach and timing:

• Single landmark timepoint (1 month post-treatment): 55.6% sensitivity, 100% specificity 1
• Serial longitudinal monitoring: 69-91% sensitivity, 100% specificity 1
• Tumor-informed approaches generally achieve higher sensitivity than tumor-agnostic methods 2
• Integration of epigenomic signatures increases sensitivity by 25-36% compared to genomic alterations alone 1

Important Caveats

Limitations to consider:

• False-negative results can occur, particularly with single timepoint testing—approximately 24.5% of ctDNA-negative patients at landmark assessment still recurred 1
• Lack of standardization across different ctDNA platforms makes direct comparison challenging 4
• Tumor-informed approaches require adequate tumor tissue for sequencing, which may not always be available 2
• Cost considerations and insurance coverage vary significantly by region and testing platform 4

Comparison to traditional markers:

• Standard serum carcinoembryonic antigen (CEA) levels did not predict recurrence (HR 1.84, p=0.18) with only 53.9% positive predictive value, demonstrating ctDNA's superiority over conventional tumor markers 1

Practical Implementation

For a patient over 50 with resected sigmoid adenocarcinoma:

1. Obtain baseline plasma sample 1 month after completion of definitive therapy (surgery ± adjuvant chemotherapy) 1
2. Consider tumor tissue comprehensive genomic profiling if available to enable tumor-informed ctDNA tracking and identify actionable alterations 3
3. If ctDNA is detectable at landmark timepoint, strongly consider intensified surveillance and discuss additional systemic therapy options 2
4. Implement serial plasma monitoring every 3-4 months for at least 2 years, particularly in high-risk patients or those with initial ctDNA positivity 1, 2
5. Maintain clinical and radiographic surveillance regardless of ctDNA status given imperfect sensitivity 1

This approach transforms post-operative management from empiric adjuvant therapy decisions to molecularly-guided, personalized treatment strategies 2, 3.