2026-07-07 | Neoadjuvant and adjuvant therapy in uveal melanoma: toward systemic control of a systemic disease.

Uveal melanoma (UM) is a biologically distinct melanoma subtype in which excellent local tumor control contrasts sharply with a high risk of delayed metastases. The frequent occurrence of distant relapse months to years after index local therapy suggests systemic dissemination early in the disease course. Inadvertently, many patients harbor minimal residual disease (MRD), comprising microscopic tumor cell populations that persist after primary tumor treatment and are undetectable by conventional imaging techniques. Historically, UM management has focused on local tumor eradication followed by surveillance, however, better understanding of the clinical trajectory of UM coupled with advances in systemic therapeutics have generated increasing interest in perioperative systemic approaches. Neoadjuvant therapy provides the opportunity to downsize the primary tumor, eliminate occult micrometastatic disease, dynamically evaluate disease biology, and inform further therapeutic decision-making. Adjuvant approaches aim to suppress or eradicate MRD following local control in patients at elevated risk of relapse. Although current evidence remains investigational or early-phase, perioperative systemic therapy represents an important research frontier in UM that holds the potential to reshape its therapeutic paradigm. Herein, we comprehensively synthesize the biological rationale, the latest data, and the ongoing clinical trials supporting perioperative systemic therapy, and discuss the emerging role of circulating tumor DNA (ctDNA) in the management of UM.

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2026-07-06 | Characteristics and Outcomes of Patients with Early or Late Uveal Melanoma Metastasis: A Review.

Uveal melanoma (UM) metastasis follows variable temporal trajectories, with recurrences ranging from rapid onset to decades post primary therapy. Outcomes after metastasis also vary significantly. Predicting high-risk "early" progressors from "late" recurring phenotypes would facilitate tailored approaches to management. A literature review was conducted to synthesise clinicopathologic and molecular predictors of metastatic latency and their impact on survival outcomes in patients with UM. Early dissemination is associated with older age, male sex, larger basal dimensions, and ciliary body involvement. Genetically, monosomy 3, 8q gain, and BAP1 loss drives a rapid-progression phenotype and poor survival. Conversely, SF3B1 mutations define a distinct late-onset cohort (median: >6 years) with persistent lifetime risk. PRAME expression significantly accelerates metastatic kinetics, even in gene expression profiling class 1 tumours. While early recurrence correlates with dismal outcomes, late-onset disease is associated with extended post-metastasis survival and greater eligibility for interventions like liver-directed therapy. Metastatic timing is related to biologic rather than stochastic determinants. Integrating molecular profiling with clinical staging and patient factors allows for more precise temporal risk stratification. These insights are essential for tailoring surveillance intensity and selecting candidates for emerging adjuvant therapies, such as tebentafusp and protein kinase C inhibitors.

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2026-07-03 | Three years of ocular proton therapy in the Netherlands, clinical results.

Uveal melanoma (UM) is a rare cancer with rising number of diagnosis (143 diagnoses in 1990 to 226 in 2023) in the Netherlands. Most patients are treated locally with Ruthenium-106 brachytherapy (±102/year). Patients were referred for proton therapy (PT) to Switzerland in the past, but PT is available in the Netherlands from January 2020 onwards. The purpose of this study is to assess the oncological and ophthalmological outcomes of the current cohort and compare with the published historic cohort. All consecutive patients with PT for UM from January 2020 till 31st December 2023 (n = 176) and the Historic Cohort (n = 101) were treated with 4 × 15 Cobalt Gray Equivalent and were included. Time to event analyses were conducted according to the Kaplan-Meier method. The median age in the current cohort was 65 years (Historic: 59, p = 0.001). Tumour stage differed between the cohorts T1 current 10% (historic 3%), T2 21% (26%), T3 55% (36%), T4 14% (36%) (p = 0.004). Tumours regressed in 2-3 years to a remnant of around 3 mm. At 3 years, OS was 78.9% (86%), DM 26.6% (17%), LF 3.5% (6%) and enucleation rate 16.8% (19%), the latter mostly because of pain and/or retinal detachment. In both cohorts, visual acuity dropped substantially after treatment (median -0.50). At 3 years, in both cohorts, around a quarter of the patients retained a vision of ≥0.3. Retinal detachment was the most common toxicity in the current cohort with 52.3%. The establishment of the HollandPTC improves access to PT for Dutch UM patients and results in additional sparing of around 40 eyes per year. Tumour regression after treatment happened gradually from 3 months to 2-3 years, often leaving a rest behind of 3-5 mm. Tumour control, eye preservation rates, and side effects are similar to the published historic cohort treated abroad.

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