Importance: Liquid biopsy is an emerging tool with the potential to change oncologic care practices. Optimal clinical applications for its use are currently undefined for surgical patients.
Observations: Liquid biopsy analytes such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) have been the most clinically studied assays and were initially limited to advanced-stage disease. In the metastatic setting, CTCs and ctDNA levels are prognostic. Although their levels correlate with treatment response, CTC-guided systemic regimen switches for nonresponders have not been shown to improve clinical outcomes. ctDNA genomic profiling has succeeded, and there are now multiple plasma-based assays approved by the US Food and Drug Administration that can detect actionable mutations to guide systemic therapy. Technological advancements in assay sensitivity have expanded the use of ctDNA to early-stage and resectable disease, allowing for detection of minimal residual disease. Postoperative ctDNA levels are a strong predictor of disease recurrence, and ctDNA detection often precedes serum carcinoembryonic antigen elevation and radiographic changes. However, its use for surveillance has not been shown to improve clinical outcomes. A promising application of ctDNA is for adjuvant therapy escalation and de-escalation. A phase 2 clinical trial demonstrated that treatment de-escalation for patients with high-risk stage II colorectal cancer and negative postoperative ctDNA had similar recurrence-free survival as patients receiving standard-of-care chemotherapy. These results suggest that ctDNA may help select patients who will benefit from adjuvant chemotherapy, and multiple clinical trials are actively underway.
Conclusions and relevance: Although uncertainties regarding the optimal use of liquid biopsy remain, it has the potential to significantly improve care for patients with cancer at all stages of disease. It is critical that surgeons understand how to use and interpret these assays, and they should be active participants in clinical trials to advance the field.