| Summary: | Abstract Objective We prospectively addressed whether patient characteristics, oncological outcomes, or metastatic risk impacted depression and anxiety in patients undergoing curative proton treatment for uveal melanoma (UM). Methods We assessed patient‐reported outcomes regarding anxiety (GAD‐7) before and 2 years after proton therapy and depression (PHQ‐9) before, 1, and 2 years after proton therapy. We performed descriptive statistics and used linear mixed effect modeling to analyze how the oncological outcome and baseline characteristics impacted anxiety and depression scores. Results Of 130 (65 female) patients included, six developed metastatic disease and three died during the 2‐year follow‐up. The mean anxiety declined from 5.86 (SE = 0.56) at baseline to 3.74 (SE = 0.46) at 2 years (β = 2.11; SE = 0.6; p < .001). Depressive symptoms decreased moderately from 4.36 (SE = 0.37) at baseline to 3.67 (SE = 0.38) 2 years later. Patients with unfavorable metastatic risk or disease progression had elevated anxiety and depression scores. Although female patients reported overall higher anxiety scores, both sexes recovered substantially and to a similar extent during the 2‐year follow‐up (β = 2.35; SE 0.87; p = .007 vs. β = 1.88; SE = 0.60; p = .002). A trend for prolonged depressive symptoms was observed in patients living alone compared to patients living with family members 1 year after the treatment (M = 5.04 [SE = 0.85] vs. M = 3.73 [SE = 0.31], β = 1.32; SE = 0.92; p = .152). Patients with high baseline anxiety levels showed initially more severe depressive symptoms, which improved significantly during follow‐up (β = 1.65; SE = 0.68; p = .017). Conclusion Most patients undergoing proton therapy for UM experienced mild, transient depressive symptoms and anxiety. Patients with high pre‐treatment anxiety, unfavorable prognoses, and patients living alone may be more vulnerable to prolonged depressive symptoms. To these patients a more tailored support could be offered at an early stage of the disease.
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