New results shed light on whether liquid or tissue biopsies are most useful for guiding targeted treatment of solid tumors. Their answer is, best to use both. In a trial of almost 1,800 patients, these researchers found a concordance rate between tissue and liquid biopsies of only 49%. But they detected substantially more actionable alterations and saw significant improvement in survival outcomes when they used both types of tests.
The study was conducted by Paolo Marchetti, MD, scientific director at the Istituto Dermopatico dell’Immacolata (IDI-IRCCS), Rome, and colleagues, and was presented during the 2025 American Association for Cancer Research (AACR) Annual Meeting.
The ROME trial was a Phase II multicenter study of 1,794 patients with advanced solid tumors. Centralized next-generation sequencing was performed on both tissue and liquid biopsies using FoundationOne CDx and FoundationOne Liquid CDx. A centralized molecular tumor board reviewed results to identify actionable alterations, with 400 patients subsequently randomized to tailored therapy or standard-of-care.
The team analyzed the concordance between tissue and liquid biopsy results in detecting actionable alterations. Concordance was defined as the detection of the same significant alterations in both biopsy types; discordance indicated detection in only one. Survival outcomes were analyzed across concordance groups.
Concordance between tissue and liquid biopsies was 49%, with actionable alterations detected exclusively in tissue biopsies in 35% of patients and exclusively in liquid biopsies in 16%. Of the 203 discordant cases, 21% were attributed to test failures, 35% to discordant high tumor mutational burden detection, 1% to microsatellite instability discrepancies, and 43.3% to differences in the detection of molecular alterations. The PI3K/PTEN/AKT/mTOR and ERBB2 pathways showed the highest discordance rates.
Test results guided therapeutic choices in 84% and 65% of cases for tissue biopsy and liquid biopsy, respectively. Patients in the concordant tissue and liquid group receiving tailored therapy had much better survival outcomes. Median overall survival was 11.05 vs. 7.70 months in the standard-of-care, and median progression-free survival was 4.93 vs. 2.80 months. In contrast, the survival benefit of targeted therapy was less pronounced or absent in patients with discordant results.
Overall, survival was higher in the group that had both types of biopsies (11.05 months), followed by the tissue-only group (9.93 months) and the liquid-only group (4.05 months). Progression-free survival followed a similar pattern, with the longest PFS observed in the group getting both types of biopsies (4.93 months) compared to 3.06 months in the tissue-only group and 2.07 months in the liquid-only group.
“Although the concordance rate between tissue and liquid biopsies was only 49%, the substantial increase in detection of actionable alterations (over 60% with the addition of liquid biopsy) and significative improvement of survival outcomes observed with combined T+L concordance strongly emphasize the importance of integrating both biopsy modalities to enhance precision oncology approaches,” they wrote.
