SUMMARY: Next-generation sequencing (NGS) has revolutionized the management of advanced cancers by enabling identification of tumor-specific genomic alterations for which targeted therapies are now available. National guidelines recommend early and routine NGS testing for patients with advanced or metastatic solid tumors to inform treatment decisions. In the United States, the five most prevalent advanced or metastatic solid tumors include advanced Non-Small Cell Lung Cancer (aNSCLC), metastatic Breast Cancer (mBC), metastatic Prostate Cancer (mPC), advanced Colorectal Cancer (aCRC), and metastatic Pancreatic Cancer (mPanC). For these malignancies, the integration of NGS has become increasingly critical in guiding targeted therapy selection and improving survival outcomes. Despite the approval of multiple targeted therapies for these malignancies, real-world utilization of NGS remains inconsistent.
In this study presented at the 2025 ASCO Annual Meeting, Chehade and colleagues, evaluated patterns in NGS testing and its timing, relative to patient mortality.
Study Overview: This retrospective analysis leveraged the Flatiron Health EHR-derived de-identified database across 280 cancer clinics, spanning data from 2011 onward. The study included patients with a diagnosis of aNSCLC, mBC, mPC, aCRC, or mPanC, all of whom had records of NGS testing and a documented date of death. The researchers identified 86,536 patients with advanced non-small cell lung cancer, 36,000 with metastatic breast cancer, 35,702 with advanced colorectal cancer, 24,105 with metastatic prostate cancer and 14,964 with metastatic pancreatic cancer. About a third of patients from each cancer group received NGS testing (NSCLC, 36.3%; breast cancer, 32.1%; colorectal cancer, 41%; prostate cancer, 30.9%; and pancreatic cancer, 35.4%).
Patients were categorized based on the interval between receipt of NGS results and death:
- More than 3 months before death
- Within 3 months of death
- After death
Key Findings Across cancer types, only 30% to 40% of patients received NGS testing. Among those who were tested and had a recorded date of death, the timing of NGS was as follows:
| Timing of First NGS | aNSCLC (N=19,958) | mBC (N=5,689) | mPC (N=3,397) | aCRC (N=8,553) | mPanC (N=3,957) |
| >3 mo before death | 72.3% | 81.6% | 85.4% | 85.0% | 71.1% |
| Within 3 mo of death | 25.6% | 16.9% | 13.5% | 13.7% | 26.5% |
| After death | 2.1% | 1.5% | 1.1% | 1.3% | 2.4% |
Notably, up to one in four patients with NSCLC or pancreatic cancer received their first NGS results within 3 months of death, a timeframe often too late for actionable therapeutic intervention.
Interpretation and Implications Despite advances in molecularly targeted therapies and growing guideline support for comprehensive genomic profiling, real-world testing patterns remain suboptimal:
- Low uptake: Only about a third of eligible patients undergo NGS testing.
- Late testing: A substantial proportion of tested patients receive results within 3 months of death.
- Missed opportunities: Many patients are never tested—or are tested too late to benefit from life-extending therapies.
These findings highlight ongoing gaps in precision oncology implementation, especially in community-based settings.
Next Steps & Recommendations To improve the utility of NGS in oncology, efforts should focus on:
- Earlier testing: At diagnosis or at first progression of advanced disease.
- Workflow integration: Embedding NGS into routine clinical pathways.
- Education: Raising awareness among clinicians and patients about the benefits of timely testing.
- Health system support: Addressing barriers such as reimbursement, turnaround times, and tissue availability.
Conclusion: Real-World Data from this large retrospective analysis reveal late-stage testing and underutilization of life-prolonging genomic profiling. This study underscores an urgent need to optimize the timing and uptake of NGS testing in patients with advanced solid tumors. Earlier and broader testing is essential to ensure patients have access to the most effective, personalized treatment strategies, and to avoid the missed potential of life-extending therapies.
Utilization and timing of first tumor next-generation sequencing testing (NGS) in patients (pts) with five most common cancers in the USA. Chehade CH, Jo Y, Ozay ZI, et al. Doi: 10.1200/JCO.2025.43.16_suppl.11014. Abstract # 11014. Presented at: ASCO Annual Meeting; May 30-June 3, 2025; Chicago.
