Circulating Tumor DNA (ctDNA) As A Minimal Residual Disease (MRD) Assessment And Recurrence Risk In Patients Undergoing Curative Intent Resection With Or Without Adjuvant Chemotherapy In Colorectal Cancer: A Systematic Review And Meta-analysis

PURPOSEEmerging data have suggested that circulating tumor DNA (ctDNA) can be a reliable biomarker for Minimal residual disease (MRD) in CRC patients. Recent studies have shown that the ability to detect MRD using ctDNA assay after curative-intent surgery will change how to assess recurrence risk and patient selection for adjuvant chemotherapy. METHODSWe performed a meta-analysis of post-operative ctDNA in Stage I-IV (oligometastatic) CRC patients after curative-intent resection. We included 23 studies representing 3,568 patients with evaluable ctDNA in CRC patients post-curative intent surgery. Data were extracted from each study to perform a meta-analysis using RevMan 5.4. software. Subsequent subgroup analysis was performed for stages I-III and oligometastatic stage IV CRC patients. RESULTSThe pooled hazard ratio (HR) for recurrence-free survival (RFS) in post-surgical ctDNA positive versus negative patients in all stages was 7.27 (95% CI 5.49-9.62) p <0.00001. Subgroup analysis revealed pooled HR of 8.14 (95% CI 5.60-11.82) and 4.83 (95% CI 3.64-6.39) for stage I-III and IV CRC, respectively. The pooled HR for RFS in post-adjuvant chemotherapy ctDNA positive versus negative patients in all stages was 10.59 (95% CI 5.59-20.06) p <0.00001. The subgroup analysis based on the ctDNA method showed a pooled HR of 8.66 (95% CI 6.38-11.75) and 3.76 (95% CI 2.58-5.48) for tumor-informed and tumor-agnostic, respectively. CONCLUSIONOur analysis emphasizes that post-operative ctDNA is a strong prognostic marker of RFS. Based on our results, ctDNA can be a significant and independent predictor of RFS. This real-time assessment of treatment benefits using ctDNA can be used as a surrogate endpoint for the development of novel drugs in the adjuvant setting.