Vitamin D Could Serve as Biomarker for Aggressive Prostate Cancer

Adam Murphy, MD

The level of vitamin D in a patient’s blood could serve as a biomarker for an aggressive form of prostate cancer, especially in men who are considering active surveillance for the disease. A new study from the Northwestern University Feinberg School of Medicine suggests a link between low levels of the vitamin and aggressive prostate cancer.

“Now we have evidence that suggests that people who have aggressive prostate cancer have lower levels of vitamin D. Vitamin D deficiency is common in men with aggressive prostate cancer,” said Adam Murphy, MD, lead author and assistant professor of Urology, Northwestern University. In addition, “Men with dark skin, low vitamin D intake, or low sun exposure should be tested for vitamin D deficiency when they are diagnosed with an elevated prostate specific antigen (PSA) level or prostate cancer. The deficiency should then be addressed after discussion between the patient and his physician,” he added. Findings were published in the Journal of Clinical Oncology.

A cross-sectional study was carried out, from 2009-2014, that was nested in a larger epidemiologic study of 1760 healthy controls and men undergoing prostate cancer screening. A cohort of 190 men were identified who had undergone radical prostatectomy. The authors assessed the relationship between adverse pathology at the time of radical prostatectomy and serum 25-hydroxyvitamin D (25-OH D) levels. Adverse pathology was defined as the presence of primary Gleason 4 or any Gleason 5 disease, or extra-prostatic extension.

Previous research has drawn an association between vitamin D levels and aggressive prostate cancer based on blood samples that were taken before treatment.

“If you place prostate cancer cells in a dish with vitamin D, growth rate slows, the cells become less invasive, and there is a greater likelihood the cells undergo apoptosis,” said Murphy. “Based on our previous research, we have strong evidence that people who have no prostate cancer have higher levels of vitamin D than those patients who had a diagnosis of prostate cancer.”

The current study provides a more direct correlation between the level of vitamin D and high-grade disease because it measured levels within a couple of months before the tumor spread beyond the prostate gland.

Eighty-seven men (45.8%) of men demonstrated adverse pathology at radical prostatectomy. The median age in the cohort was 64.0 years. On univariate analysis, men with adverse pathology demonstrated lower median serum of vitamin D levels (22.7 versus 27.0 ng/mL, P = .007) compared with their counterparts. On multivariate analysis, controlling for age, serum PSA, and abnormal digital rectal examination, vitamin D levels less than 30 ng/mL was associated with increased odds of adverse pathology (odds ratio, 2.64; 95% CI, 1.25-5.59; P = .01).

Murphy noted that the disparities seen in prostate cancer, especially among African-American men, may be explained by the relationship between the vitamin and prostate cancer. Previous research by Murphy demonstrated that African-American men who live in low sunlight locations are up to 1.5 times more likely to have vitamin D deficiency than Caucasian men.

Murphy recommends that because vitamin D is a biomarker for bone health and aggressiveness of other diseases, all men should check their levels.

The relationship between serum vitamin D and PSA levels may be due to the effect of vitamin D on prostate cancer cell proliferation and differentiation. The findings showed that the largest association of low serum vitamin D was among men with intermediate-risk disease at diagnosis. This group may benefit most from normalization of their vitamin D levels with regards to their disease.

Future studies should evaluate the risk of vitamin D levels and supplementation on prostate cancer pathologic aggressiveness with regard to NCCN risk stratification, especially for men being considered for active surveillance, as vitamin D levels may be a useful biomarker in this population.

“Vitamin D has many roles in the body. It’s been associated with bone health, rheumatoid arthritis, and other types of cancer. So, for various reasons, it’s important to correct vitamin D deficiency,” said Murphy. “There’s enough evidence from small clinical studies and large preclinical studies suggesting that vitamin D deficiency increases the aggressiveness of prostate cancer. So replacing vitamin D in people who are deficient makes a lot of sense.”

Nyame YA, Murphy AB, Bowen DK, et al. Associations between serum vitamin D and adverse pathology in men undergoing radical prostatectomy. [published online before print February 22, 2016]. J Clin Oncol. doi: 10.1200/JCO.2015.65.1463.