Real-world clinical utility of tumor whole-genome sequencing in solid cancers.

This study reports real-world implementation of routine paired tumor–normal whole-genome sequencing (WGS) for solid tumors in a comprehensive cancer center, focusing on feasibility, diagnostic yield, and clinical impact.

Key points:

• Feasibility and logistics
  • • WGS was successfully completed in 89% of 888 consecutive patients.
  • • Median turnaround time was 6 working days, compatible with routine clinical decision-making.
• Actionable findings
  • • 73% of patients had potentially actionable biomarkers:
    • • 27% linked to reimbursed therapies.
    • • 63% linked to experimental therapies (e.g., trial options).
  • • Overall, 41% of all tested patients experienced a direct clinical consequence from WGS (treatment choice or diagnostic clarification).
• Treatment uptake and outcomes
  • • Within 1 year of testing:
    • • 40% of patients with an identified reimbursed biomarker-based option and
    • • 19% of those with only experimental options actually started biomarker-informed therapy.
  • • Patients who received biomarker-informed treatment had a 31% longer median overall survival, corresponding to +96 days compared with those who did not.
  • • In patients without prior systemic therapy:
    • • Biomarker-informed treatment led to significantly longer overall survival (median not reached),
    • • versus 427 days with non–biomarker-informed systemic therapy,
    • • and 214 days with no systemic therapy.
• Cancers of unknown primary (CUP)
  • • In 123 CUP patients, WGS:
    • • Contributed to a diagnostic solution or identified reimbursed, biomarker-driven treatment options in 67%.
    • • Led to 68% of these patients initiating tumor-type–specific therapy.
• Germline findings
  • • Clinically relevant pathogenic germline variants were identified in 6.5% of patients, with implications for hereditary cancer risk management.

Overall, routine WGS in solid tumors was operationally feasible, identified clinically meaningful biomarkers in a majority of patients, influenced management in roughly two-fifths, and was associated with improved survival in those receiving biomarker-informed treatment, including substantial benefit in cancers of unknown primary.