Vitamin D deficiency is associated with a worse prognosis in metastatic melanoma

Abstract

Vitamin D deficiency (≤20 ng/mL) is associated with an increased incidence and worse prognosis of various types of cancer including melanoma. A retrospective, single-center study of individuals diagnosed with melanoma from January 2007 through June 2013 who had a vitamin D (25(OH)D3) level measured within one year of diagnosis was performed to determine whether vitamin D deficiency and repletion are associated with melanoma outcome. A total of 409 individuals diagnosed with histopathology-confirmed melanoma who had an ever measured serum 25(OH)D3 level were identified. 252 individuals with a 25(OH)D3 level recorded within one year after diagnosis were included in the study and the individual and melanoma characteristics such as age, sex, Breslow thickness, ulceration, stage, mitotic rate, and LDH were obtained from the medical record. A worse melanoma prognosis was associated with vitamin D deficiency (P=0.012), higher stage (P<0.001), ulceration (P=0.001), and higher mitotic rate (P=0.001) (HR 1.93, 95% CI 1.15-3.22). In patients with stage IV metastatic melanoma, vitamin D deficiency was associated with significantly worse melanoma-specific mortality (adjusted HR 2.06, 95% CI 1.10-3.87). Patients with metastatic melanoma who were initially vitamin D deficient and subsequently had a decrease or ≤20 ng/mL increase in their 25(OH)D3 concentration had significantly worse outcomes (HR 4.68, 95% CI 1.05-20.88) compared to non-deficient patients who had a >20 ng/mL increase. Our results suggest that initial vitamin D deficiency and insufficient repletion is associated with a worse prognosis in patients with metastatic melanoma.

Keywords: 25(OH)D3; melanoma; vitamin D deficiency.

Figure 1. Patient Selection for Study Eligibility

Figure 2. Comparison between Initial and Change in Vitamin D Levels

Lower initial 25(OH)D3 levels were associated with a higher increase in vitamin D on subsequent measurements (P<0.0001). A linear regression (change in vitamin D level = -0.66*(initial vitamin D level) + 32, R² = 0.25) was fit to the entire dataset (N=168) of individuals who had an initial 25(OH)D3 level measured within one year after diagnosis and also had a 25(OH)D3 measurement following supplementation. Individuals with non-metastatic disease are color-coded with empty green circles, while those with metastatic disease are color-coded with filled red circles. Statistically significant linear associations were obtained for the non-metastatic (R² = 0.21, P=0.0006) and metastatic groups (R² = 0.26, P<0.0001) separately as well.