Simple SummaryUveal melanoma (UM) is an eye cancer that will spread to other parts of the body in almost 50% of cases, most commonly to the liver. Regular liver scans can lead to early detection of UM metastases. Current guidelines recommend such liver surveillance in UM patients with a ‘high risk’ of metastasis but do not specify how this group is defined. Several different systems can estimate a patient’s risk of dying from metastatic UM. Our study compared the accuracy of different UM prognostic systems when used to target enrolment into surveillance programmes and suggests that some systems could relieve some patients from unnecessary scans and conserve resources. We found that using the Liverpool Uveal Melanoma Prognosticator Online III (LUMPOIII) could offer equal sensitivity and greater specificity than other systems. We suggest guidance for its use, even when genetic testing is not provided. This study provides important context for revising the clinical guidelines for stratification for surveillance in UM.AbstractUveal melanoma (UM) metastasises in ~50% of patients, most frequently to the liver. Surveillance imaging can provide early detection of hepatic metastases; however, guidance regarding UM patient risk stratification for surveillance is unclear. This study compared sensitivity and specificity of four current prognostic systems, when used for risk stratification for surveillance, on patients treated at the Liverpool Ocular Oncology Centre (LOOC) between 2007–2016 (n= 1047). It found that the Liverpool Uveal Melanoma Prognosticator Online III (LUMPOIII) or Liverpool Parsimonious Model (LPM) offered greater specificity at equal levels of sensitivity than the American Joint Committee on Cancer (AJCC) system or monosomy 3 alone, and suggests guidance to achieve 95% sensitivity and 51% specificity (i.e., how to detect the same number of patients with metastases, while reducing the number of negative scans). For example, 180 scans could be safely avoided over 5 years in 200 patients using the most specific approach. LUMPOIII also offered high sensitivity and improved specificity over the AJCC in the absence of genetic information, making the result relevant to centres that do not perform genetic testing, or where such testing is inappropriate or fails. This study provides valuable information for clinical guidelines for risk stratification for surveillance in UM.