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Paired tissue-liquid biopsy CGP approaches: Driving broader enrollment and better outcomes

21 Jan 2026

Summary: 

  • Paired tissue–liquid biopsy CGP improves mutation detection and expands patient eligibility compared with tissue-only testing.
  • Liquid biopsy (cfDNA) offers a non‑invasive, rapid, and accessible option that captures actionable variants when tissue is insufficient or unavailable.
  • Combining tissue and plasma testing boosts clinical trial enrollment, with studies showing meaningful percentages of actionable variants found only in liquid biopsy.
  • Recent FDA guidance supports cfDNA in clinical trials, accelerating adoption of plasma-based companion diagnostics.
  • Labcorp’s validated tissue and plasma CGP assays streamline enrollment, reduce the need for bridging studies, and support better precision‑oncology outcomes.

Comprehensive genomic profiling (CGP) of tumor tissue is central to precision oncology, enabling detection of actionable mutations to inform treatment decisions. Significant strides have been made in increasing how many patients are eligible for tissue testing and in the number of targeted therapies available; however, tissue testing success rates vary by disease type and may miss known guideline-based mutations.1-3 By integrating liquid biopsy with tissue CGP workflows, sponsors can expand eligibility, uncover additional mutations and accelerate timelines—ultimately improving outcomes for patients and trials alike. 

Headshot of Jennifer Dickey

Jennifer Dickey, PhD, RAC
Senior Director, Head of Regulatory, PGDx

Dr. Dickey leads regulatory strategy for Labcorp’s PGDx precision oncology portfolio, leveraging over 20 years of experience in regulatory review and shaping NGS-based diagnostics.
 

Q&A: Complementing tissue profiling workflows with liquid biopsy to empower clinical trials
 

What is cell-free DNA (cfDNA) and why is it important in precision medicine?

cfDNA refers to fragments of DNA circulating in the bloodstream, often released by cancer cells. It enables liquid biopsy testing, which is transforming precision medicine by offering non-invasive, flexible and accessible diagnostic options.

How does liquid biopsy complement tissue-based testing and enhance clinical trial success?

A paired tissue-plasma strategy expands patient access and trial flexibility while uncovering actionable mutations that tissue-only testing may miss. One recent study showed liquid biopsy testing identified clinically actionable variants not detected by solid-tissue testing in 9.3% of patients.2 This approach supports broader geographic identification and enrollment of eligible patients and enables companion diagnostic (CDx) development strategies that capture the widest patient population. Plasma-based testing is particularly valuable for patients without sufficient tissue, offering additional mutation detection and actionable insights to optimize precision oncology outcomes.

“Using a matched tissue-plasma approach enables more flexibility in clinical trials, enrollment across broader geographies, and allows for a CDx strategy that captures the broadest patient population.”
— Jennifer Dickey, PhD, RAC, Head of Regulatory, PGDx


What are the limitations of a tissue-only approach in clinical trials?

  • Limited patient population–Many patients may not qualify for tissue-only precision oncology pathways
  • Complex bridging studies–Differences between clinical trial assays and the final CDx can complicate approvals
  • Lack of pre-analytical data–Missing standardized data impedes cross-study comparisons and delays plasma CDx approvals

What regulatory developments support cfDNA use in clinical trials?

The FDA released guidance in 2024 to help sponsors use cfDNA in trials and support marketing approvals.4 The number of approved tissue and plasma-based CDx has also increased.

Labcorp research solutions

Labcorp offers validated, high-sensitivity tissue and liquid-biopsy testing options designed to enable a paired research strategy and support your trial from enrollment to approval. These assays can expand trial participation and results while eliminating the need for a bridging study.
 

Labcorp Tissue Complete powered by PGDx elio tissue complete

  • 505-gene panel detects SNVs, indels, amplifications, translocations, MSI and TMB
  • FDA 510(k) cleared and CE-marked
  • Validated for FFPE tissue samples with minimal DNA input and high success rate across diverse sample types
  • Available as PGDx elio distributed kitted solutions to empower in-house testing workflows
     

Labcorp Plasma Focus powered by PGDx elio plasma focus Dx

  • 33-gene panel detects SNVs, indels, amplifications and translocations from low-input cfDNA
  • FDA de novo authorized
  • Enables testing for patients with limited or inaccessible tissue
  • Available as PGDx elio distributed kitted solutions to empower in-house testing workflows
     

References

  1. Volders PJ, Aftimos P, Dedeurwaerdere F, et al. A nationwide comprehensive genomic profiling and molecular tumor board platform for patients with advanced cancer. npj Precis Onc. 2025;9(66). doi:10.1038/s41698-025-00858-0
  2. Iams WT, Mackay M, Ben-Shachar R, et al. Concurrent tissue and circulating tumor DNA molecular profiling to detect guideline-based targeted mutations in a multicancer cohort. JAMA Netw Open. 2024;7(1):e2351700. doi:10.1001/jamanetworkopen.2023.51700
  3. Raez LE, Brice K, Dumais K, et al. Liquid biopsy versus tissue biopsy to determine front line therapy in metastatic non-small cell lung cancer (NSCLC). Clin Lung Cancer. 2023;24(2):120-129. doi:10.1016/j.cllc.2022.11.007
  4. Use of circulating tumor deoxyribonucleic acid for early-stage solid tumor drug development; Guidance for Industry. U.S. Food and Drug Administration. November 2024. https://www.fda.gov/media/158072/download