OBJECTIVES: This study evaluates the impact of the timing of next-generation sequencing (NGS) on real-world overall survival (rwOS) in colorectal cancer (CRC) patients and aims to understand its importance in driving treatment (tx) decisions.

METHODS: This retrospective analysis of the Tempus real-world multimodal database included patients ≥18 years, diagnosed with CRC until 2024 (median year: 2019). For rwOS analysis, index date was defined as first-line (1L) tx initiation and patients were censored at death, last known followup, or 3 years post-index.

RESULTS: Among 2,293 CRC patients, median age at diagnosis was 58.4 years; 57% were men, 82% white, 12% African American, and 63% received care at non-academic centers. Most were diagnosed at Stage 3 (23%) or Stage 4 (68%) and were microsatellite stable (96%). 1,884 patients had a recorded 1L tx with approximately 90% of those patients receiving a chemotherapy regimen without an NGS-informed therapy, despite approvals of 1L targeted tx (e.g. cetuximab).
A random forest classifier trained on patients who received NGS results before 1L initiation, identified time from biopsy to NGS results receipt as the most important clinical feature in determining 1L tx. The timeline from diagnosis to receiving NGS results was segmented: diagnosis to biopsy (28d), biopsy to NGS test order (51d), NGS test order to sequencing run (11d), and sequencing run to NGS report dissemination (3d). A notable delay in ordering the NGS test post-biopsy was observed, with some tests not ordered until after a 1L progression event, contributing to longer times. Stage 4 patients who received NGS results within ~2 months of their biopsy had a significant overall survival advantage (p = 0.018, log-rank test).

CONCLUSIONS: Early NGS testing is associated with increased rwOS in CRC patients, underscoring the importance of timely NGS testing in guiding tx decisions and improving outcomes.

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