Retrospective Comparison of Operational Metrics Across Diagnostic Approaches for Molecular Testing in Lung and Colon Cancers in a Community-Based Setting.

CONTEXT.—: Identifying oncogenic driver mutations in non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) is critical for targeted therapies, requiring accurate and timely molecular testing.

OBJECTIVE.—: To compare turnaround time (TAT; days from order to results), quantity not sufficient (QNS) rate, and detection rates of National Comprehensive Cancer Network-recommended alterations in NSCLC (epidermal growth factor receptor [EGFR]; MET proto-oncogene, receptor tyrosine kinase [MET] exon 14 skipping; ROS proto-oncogene 1, receptor tyrosine kinase [ROS1]; ALK receptor tyrosine kinase [ALK]; ret proto-oncogene [RET]; erb-b2 receptor tyrosine kinase 2 [ERBB2] mutations; neurotrophic receptor tyrosine kinase 1, 2, and 3 [NTRK1/2/3]; B-Raf proto-oncogene, serine/threonine kinase [BRAF]; KRAS proto-oncogene, GTPase [KRAS] [G12C]) and CRC (RET; ERBB2 amplification; NTRK1/2/3; BRAF; KRAS; NRAS proto-oncogene, GTPase [NRAS]; microsatellite instability) using 3 testing algorithms: in-house single-gene panel (SGP; 5 of 9 NSCLC, 4 of 7 CRC alterations); ThermoFisher Oncomine Focus Assay (OFA; covers all NSCLC, 6 of 7 CRC alterations); and send-out next-generation sequencing (SO-NGS; all National Comprehensive Cancer Network alterations).

DESIGN.—: Three hundred fourteen tumors (181 NSCLC, 133 CRC) were tested with SGP, 377 (239 NSCLC, 138 CRC) with OFA, and 238 (185 NSCLC, 53 CRC) with SO-NGS.

RESULTS.—: NSCLC TATs were 7.6 days (SGP), 11.1 days (OFA), and 11.9 days (SO-NGS). QNS rates were 10.4% (SGP), 6.3% (OFA), and 11.9% (SO-NGS). Detection rates were 19.8% (SGP), 26.8% (OFA), and 29.4% (SO-NGS). For CRC, TATs were 6.0 days (SGP), 10.1 days (OFA), and 10.2 days (SO-NGS). QNS rates were 0.8% (SGP), 0.7% (OFA), and 7.5% (SO-NGS). Detection rates were 62.9% (SGP), 58.4% (OFA), and 56.5% (SO-NGS).

CONCLUSIONS.—: SGP provides the fastest TAT but lower detection and higher QNS rates in NSCLC. OFA balances TAT, QNS, and detection, whereas SO-NGS offers comprehensive detection with longer TAT and higher QNS. An optimized assay combining SGP's speed, OFA's reliability, and SO-NGS's comprehensiveness could improve outcomes.