Despite the benefits of early detection of cutaneous melanoma (CM), population-wide skin screening is not recommended, as there is no evidence that it saves lives. Further, population-wide screening for CM can lead to overdiagnosis, or the detection of disease upon screening that otherwise would not have caused harm. Current Australian guidelines recommend that only those at above-average risk for melanoma undergo screening for skin cancers. However, the rate of non-adherence in Australia (i.e., high-risk people going unscreened while low-risk people are screened) can be as high as 40%. The evidence from diseases other than melanoma (e.g. breast cancer) suggests that people can be reluctant to reduce the amount of disease screening they receive.
Phenotypic risk scores for CM are available and are recommended by the Royal Australian College of General Practitioners of Australia to identify high-risk individuals for targeted screening. CM is also highly heritable (~50%), and a newly generated polygenic risk score (PRS) can perform comparably to clinical risk scores (PRS + age + sex c-index 0.701 (0.675 - 0.727) vs clinical risk score c-index 0.729 (95% CI: 0.704–0.754) in QSkin). We will report on the performance of this PRS when combined with existing phenotypic risk factors, and evaluate its performance against existing real-world risk models for melanoma.
We will also describe a newly funded three-armed randomised controlled trial, Q-Inform. Q-Inform will determine if either phenotypic or genetic (PRS) risk-stratification can improve adherence to recommended skin screening practices. This study will help determine if risk-targeted screening is achievable, and assess if such a program can cause unnecessary harm (e.g. distress).