Liquid Biopsy Outperforms Tissue-Based Testing: Colorectal Cancer Study Results

Colorectal cancer (CRC)is common worldwide, and treatment options need to be selected carefully for each patient. Approximately 30-40% of patients with colorectal cancer are diagnosed at the metastatic stage . In advanced disease, identifying mutations in RAS and BRAF is crucial for assessing the disease course and likely treatment response.

These mutations are usually analyzed using tissue biopsy , while recent advances in liquid biopsy have brought a new diagnostic and monitoring tool for patients with cancer. By analyzing circulating tumor DNA (ctDNA), liquid biopsy has the potential to detect mutations with greater sensitivity and broader coverage.

Liquid Biopsy Detects Mutations Missed by Tissue Biopsy

Journal of Clinical Oncologypublished a study on 4 February in which Stintzing and colleagues investigated whether liquid biopsy was a better biomarker than tissue biopsy . The study aimed to compare liquid biopsy and tissue biopsy results in patients enrolled in the FIRE-4 clinical trial.

Details of the FIRE-4 Trial

This analysis was conducted within FIRE-4, a clinical trial based in Germany and Austria. In FIRE-4, patients with metastatic colorectal cancer classified as RAS wild-type (RASwt) by tissue biopsy were assigned to two groups:

• FOLFIRI (Fluorouracil, Folinic Acid and Irinotecan) + Cetuximab Treatment: Patients received this regimen until disease progression or toxicity prevented them from continuing.
• Maintenance Treatment After FOLFIRI + Cetuximab: After a defined period, patients switched to 5-FU and bevacizumab .

All patients underwent liquid biopsy before and during treatment . ONCOBEAM RAS testing and droplet digital polymerase chain reaction (ddPCR) technology were used to analyze mutations.

Key Findings

• The study included 672 patients, of whom 540 had evaluable liquid biopsy data.
• Among patients classified as RAS wild-type by tissue biopsy, 13% (70 patients) were found to have RAS mutations on liquid biopsy.
• A BRAF V600E mutation was detected in 7% of patients (38 patients).

Clinical Outcomes

Patients with RAS mutations had poorer outcomes than those with RAS wild-type disease:

• Median progression-free survival (PFS): 9.0 months vs. 11.5 months (HR = 1.66, P < .001)
• Median overall survival (OS): 22.1 months vs. 33.6 months (HR = 1.85, P < .001)

Patients with RAS mutations benefited from an early switch to maintenance treatment:

• Median PFS: 10.1 months vs. 6.4 months (HR = 0.82, P = .54)
• Median OS: 24.9 months vs. 16.3 months (HR = 0.57, P = .10)

Patients with BRAF V600E mutations had the poorest outcomes:

• Median PFS: 5.4 months
• Median OS: 12.0 months

Conclusion: Could Liquid Biopsy Be More Sensitive Than Tissue Biopsy?

This study suggests that liquid biopsy may be more sensitive than tissue biopsy in metastatic colorectal cancer.

• Mutations not detected by tissue biopsymay be identified through liquid biopsy.
• Tumor heterogeneity may be reflected more accurately.
• Treatment response and progression may be monitored more sensitively.

These findings suggest that liquid biopsy could play a crucial role in guiding patients toward more appropriate treatments. Particularly for patients in whom tissue biopsy is not possible or provides insufficient material, adopting liquid biopsy as a standard diagnostic method could influence future clinical decisions.