Lower levels of vitamin D in patients with melanoma were associated with poorer survival, independent of effects from systemic inflammation indicated by simultaneous C-reactive protein (CRP) measures, according to researchers.

Multivariate analysis showed that vitamin D level was associated with overall survival (OS) (hazard ratio, 1.02 per unit decrease of vitamin D; 95% confidence interval, 1.01-1.04; P = .005), melanoma-specific survival (MSS) (HR, 1.02; 95% CI, 1.00-1.04; P = .048), and disease-free survival (DFS) (HR, 1.02; 95% CI, 1.00-1.04; P = .043). Patients with a vitamin D level less than 16 mg/mL were 2.0 times more likely to die of all-cause disease than were patients with a higher level (95% CI, 1.50-2.66; P less than .001), investigators reported (J Clin Oncol. 2016 Mar 21. doi: 10.1200/JCO.2015.64.1357).

“Importantly, after adjustment for CRP, vitamin D remained an independent predictor of OS, MSS, and DFS. This suggests that, although blood levels of vitamin D and CRP are highly correlated with each other, each independently predicts clinical outcome in patients with melanoma,” wrote Dr. Shenying Fang of the University of Texas MD Anderson Cancer Center, Houston, and colleagues.

Although the role of the biomarkers in disease remains unclear and warrants further research, the authors added, “these data suggest that interventions to increase vitamin D or to reduce [systematic inflammatory response] and CRP could ultimately benefit patients with melanoma.”

Previous research has demonstrated an association between vitamin D deficiency and advanced melanoma stage, but investigations of vitamin D blood levels and melanoma risk have yielded inconsistent results. The researchers examined confounders, such as systemic inflammatory response (assessed by simultaneous CRP measurement), age, disease stage, and blood draw season to assess the relationship between vitamin D level and melanoma outcomes.

Decreased vitamin D was significantly associated with higher patient age, increased primary tumor thickness, ulcerated tumors, advanced-stage disease at blood draw, and increased CRP. Blood drawn in the fall/winter had lower vitamin D levels than that of spring/summer, reflecting average differences in sun exposure. These factors were included in the multivariable model.

A vitamin D level less than 20 mg/mL is considered deficient, and deficient levels were significantly associated with poorer OS and DFS but not with poorer MSS. At levels below the optimal cutoff, determined by recursive partitioning, of 16 mg/mL, patients had poorer OS (HR, 2.0; 95% CI, 1.50-2.66; P less than .001), MSS (HR, 1.76; 95% CI, 1.22-2.53; P = .003), and DFS (HR, 1.62; 95% CI, 1.04-2.53; P = .036) on univariate analysis, and associations remained significant on multivariable analysis.

The hospital-based investigation evaluated peripheral blood samples collected from 1,042 non-Hispanic white patients with melanoma from 1997 to 2009.

Dr. Fang reported having no disclosures. Several of his coauthors reported financial ties to industry sources.