Uveal melanoma: A retrospective cohort study of long-term outcomes and impact of surveillance imaging intervals on metastatic burden to guide risk-adapted surveillance strategies.

Abstract

e21578 Background: Uveal melanoma (UM) is associated with a high lifetime risk of metastatic disease, characterized by prolonged dormancy periods (sometimes decades) and strong hepatic predilection. Molecular risk stratification using gene expression profiling (GEP) and Preferentially Expressed Antigen in Melanoma (PRAME) expression is commonly used for prognostication and surveillance discussions. However, there is a general lack of consensus on optimal surveillance imaging modalities and intervals with varied practices across experts and institutions. More frequent imaging may not necessarily lead to clinically actionable interventions and can generate considerable anxiety for patients. Methods: We conducted a single institution, retrospective cohort study of UM patients seen between 2014-2025. Of 619 patients total, 440 met the inclusion criteria of stage I–III UM at diagnosis with at least one year follow-up. We captured metastatic events and correlated with clinical stage, GEP class and PRAME status. Surveillance imaging intervals, calculated from the last normal imaging study to the first scan concerning for metastasis, were categorized as 6, 12, or >18 months. Metastatic tumor burden, including size (e.g. LDLHM = largest diameter of the largest hepatic metastasis) and number of metastases, was compared across surveillance imaging intervals for different molecular risk categories. Results: With a median follow-up of 4.4 years (inter-quartile range [IQR] 2.5-7.0), 83 of 440 patients (19%) developed distant metastases (DM). DM occurred across all GEP risk categories (class 1A - 10/109 [9%]; class 1B - 6/66 [9%] and class 2 - 49/121 [40%]) and most commonly involved the liver (86%) and/or lungs (17%). Among these 83 patients, median time-to-metastasis was 26 months (IQR 19-46) overall, 35 months (IQR 23-49) in GEP class 1A/1B and 23 months (IQR 17-33) in class 2. GEP class 2 was also associated with greater hepatic tumor burden at time of first detection, including larger tumors (median LDLHM 19 mm [IQR 10 – 32] for class 2 vs 10 mm [IQR 7 – 15] for class 1A/B; p = 0.14) and more tumors (median number of hepatic metastases 5 [IQR 2-10+] in class 2 vs 3 [IQR 2-3] in class 1A/B; p = 0.02). Median LDLHM for class 2 tumors was 13 mm [IQR 8-22] and 31 mm [IQR 23-52] with 6- and 12-months surveillance intervals, respectively (p = 0.009). Median LDLHM was 10.5 mm [IQR 8.25-17.5] for class 1A/1B with 12-months surveillance intervals. Conclusions: GEP risk categories influence biologic behavior of UM metastases, with metastases developing more commonly and sooner and with greater tumor burden for GEP class 2 vs class 1A/1B, warranting a risk-adapted surveillance approach. Our data support 6-months surveillance imaging interval for GEP class 2 tumors and 12 -months interval for GEP classes 1A and 1B.