A groundbreaking study has revealed that combining tissue and liquid biopsies to guide cancer treatment decisions significantly improves survival outcomes for patients with advanced solid tumors.
Results from the phase II multicenter ROME trial, presented at the American Association for Cancer Research (AACR) Annual Meeting 2025, demonstrate that patients receiving tailored therapy based on matching genomic alterations found in both biopsy types experienced substantially better outcomes compared to those receiving standard care or treatments guided by a single biopsy method.
Superior Outcomes with Concordant Biopsy Results
Between November 2020 and August 2023, researchers enrolled 1,794 adult patients with advanced or metastatic solid tumors who were on their second or third line of treatment. Each patient provided samples for both liquid (FoundationOne Liquid CDx) and tissue (FoundationOne CDx) biopsies, with results analyzed by a molecular tumor board.
The study identified 400 patients with actionable genomic alterations. Among these, 49.2% (197 patients) had the same actionable alterations detected in both tissue and liquid biopsies (T+L group), while 34.7% (139 patients) had alterations found exclusively in tissue samples and 16% (64 patients) exclusively in liquid biopsies.
For patients in the T+L group receiving tailored therapy, the median overall survival reached 11.05 months compared to 7.7 months for those receiving standard care—representing a 26% reduction in death risk. Progression-free survival was similarly improved at 4.93 months versus 2.8 months, reflecting a 45% reduction in progression risk.
"The superior outcomes observed in patients with concordant biopsy findings highlight the potential of combined molecular profiling approaches to optimize patient selection for tailored therapies," explained Dr. Paolo Marchetti, scientific director at the Istituto Dermopatico dell'Immacolata (IDI-IRCCS) in Rome, Italy, who presented the trial results.
Comparing Biopsy Approaches
The study revealed significant differences in survival based on which biopsy method detected actionable alterations. Overall survival was highest in the T+L group (11.05 months), followed by the tissue-only group (9.93 months), and lowest in the liquid-only group (4.05 months). Progression-free survival followed the same pattern: 4.93 months for T+L, 3.06 months for tissue-only, and 2.07 months for liquid-only.
The 12-month overall survival rate was 47.8% in the T+L group receiving tailored therapy versus 38.8% in the standard-of-care group. The objective response rate was also superior at 20% versus 11.8%.
Understanding Biopsy Discordance
The study found that tissue and liquid biopsies often yield different results, with only 49% concordance in detecting actionable alterations. This discordance stems from the inherent limitations of each approach.
"Tissue biopsies get a sample directly from the tumor but require an invasive surgical procedure. Since the sample is taken from a specific area of the tumor, the test may miss mutations in other parts of the tumor," Dr. Marchetti explained. "Liquid biopsies only require a blood sample but may not detect mutations from tumors that do not shed enough cells into the bloodstream."
Discordant cases were attributed to several factors:
- Discrepancies in molecular alteration detection (43.3%)
- High tumor mutational burden (35%)
- Microsatellite instability (1%)
- Test failures (21%)
The two pathways with the highest discordance rates were PI3K/PTEN/AKT/mTOR and ERBB2.
Clinical Implications for Precision Oncology
The findings suggest that integrating both biopsy modalities could significantly enhance precision oncology approaches. While the concordance rate between tissue and liquid biopsies was only 49%, the combined approach substantially increased detection of actionable alterations—by over 60% with the addition of liquid biopsy.
"Investigating discordance in molecular alterations between tissue and liquid biopsies is critical for precision oncology," noted Dr. Marchetti. "Tumor characteristics in different sites can lead to the identification of different clinical actionable targets, yet current biopsy strategies often fail to capture this heterogeneity."
Future Directions
Dr. Marchetti emphasized the need to develop strategies addressing discordance, such as incorporating additional molecular profiling methods or enhancing the sensitivity and specificity of existing technologies. His team plans to validate these findings in a multicenter cohort using integrated liquid and tissue profiling at serial timepoints.
"Expanding the analyses to account for more factors, such as disease subtype, metastatic sites, and biopsy location could help define a new, more effective diagnostic pathway," he added.
Study Limitations
The researchers acknowledged several limitations, including the exploratory nature of the analysis and the absence of predefined statistical power for subgroup comparisons. Samples for tissue and liquid biopsies were taken at different times, which may have affected results. Additionally, the relatively small size of certain subgroups, particularly the liquid-only group, may limit the robustness of conclusions for these populations.
The ROME trial was funded by multiple pharmaceutical companies, including Roche, Bristol Myers Squibb, Incyte, Novartis, Pfizer, Takeda, Merck, and Eli Lilly and Company.
By addressing the challenges of discordance and leveraging the strengths of both biopsy modalities, these findings suggest that future precision oncology strategies could significantly enhance clinical outcomes for patients with advanced cancers.
