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Research · 03 of 05

A 40-gene profile claims to pick out high-risk cSCC for adjuvant radiotherapy

Do not base adjuvant radiotherapy decisions on a gene expression profile yet; keep using clinicopathological staging and MDT review.

Design
Retrospective validation cohort
Population
572 patients with high-risk cutaneous squamous cell carcinoma
Primary outcome
Metastasis and local recurrence risk by i40-GEP class
Effect
Class 1A NPV >95%; Class 2B (12.9%) 3-year MFS 66.2%

An integrated score combining a 40-gene expression profile with five clinicopathological features — immunosuppression, site, differentiation, diameter and perineural invasion — was validated retrospectively in 572 high-risk cutaneous squamous cell carcinomas.

The score separated metastatic and local recurrence risk (p < 0.001). The lowest class had over 95% negative predictive value. The highest class, 12.9% of patients, had 3-year metastasis-free survival of 66.2% and appeared to benefit from adjuvant radiotherapy.

If confirmed, a test like this could spare low-risk patients radiotherapy and target it to those most likely to benefit. But the radiotherapy benefit comes from a retrospective, non-randomised comparison, and the test is proprietary and not available in India.

  • Keep staging with existing systems (BWH or AJCC) as the basis of decisions.
  • Record the five clinicopathological features in every high-risk cSCC report.
  • Discuss adjuvant radiotherapy in a multidisciplinary meeting, not on a test result alone.
  • Treat the gene profile as an adjunct under evaluation.

Why it matters

It points to a way to target radiotherapy in cSCC, where current staging over- and under-treats.

Don't overread it

The radiotherapy benefit is from a retrospective subgroup, not a randomised comparison.

The statistics, in plain English

A negative predictive value above 95% means fewer than 1 in 20 patients called low risk went on to the outcome. That depends on how common the outcome was in this cohort and may be lower elsewhere. No hazard ratio for the radiotherapy effect was reported in the abstract.

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