Low Vitamin D Linked to Adverse Prostate Pathology – MedPage Today

Low serum vitamin D was associated with a significantly increased risk of adverse pathology in men with localized prostate cancer undergoing radical prostatectomy, according to a study published online in the Journal of Clinical Oncology.

At the time of surgery, 45.8% of the cohort of 190 men demonstrated adverse pathology – defined as the presence of primary Gleason 4, any Gleason 5 disease, or extraprostatic extension. Those with serum 25-(OH)D <30 ng/mL were 2.64 times more likely to be affected than men with higher levels of vitamin D (95% CI 1.25-5.59; P=0.01).

The association was strongest among men with intermediate-risk disease.

“Men with sustained vitamin D deficiency are likely at risk of aggressive forms of prostate cancer,” corresponding author Adam B. Murphy, MD, of Northwestern University in Chicago, told MedPage Today in an email.

Regarding the generalizability of the findings, he said, “This would include most African-American men, men living in the northern one third of the country, most men who avoid dairy and fatty fish intake (lactose intolerance/vegans etc.), and men who cover their skin. This represents a significant portion of the country.”

The cross-sectional study was conducted between 2009 and 2014, with subjects drawn from within a large epidemiologic study of 1,760 healthy controls and men undergoing prostate cancer screening. The Chicago-based cohort included 190 men with a median age of 64 years who had undergone radical prostatectomy within 1 year of diagnosis of clinically localized prostate cancer.

Men who had received either adjuvant therapy prior to radical prostatectomy or treatment at a nonstudy institution were excluded from analysis.

At baseline, 34.7% of the cohort met National Comprehensive Cancer Network (NCCN) criteria for very low or low-risk disease. At prostatectomy, extraprostatic disease (pT3) was seen in 31.6% of the men, and on final pathology, 10.0% had seminal vesicle invasion.

On stratified analysis, serum vitamin D level (OR 0.92; 95% CI 0.86-0.98; P=0.01) and serum 25-OH D<30 ng/mL at diagnosis (OR 3.62, 95% CI 1.15-11.46, P=0.03) were significantly associated with adverse pathology in men with intermediate-risk prostate cancer at diagnosis. A similar but nonsignificant association was also observed in men with low and very-low risk disease preoperatively.

Given that the majority of prostate cancer is diagnosed when it is still localized to the prostate gland, and that current treatment paradigms are shifting in favor of active surveillance of low-risk PCa, the authors suggested that high-risk populations, such as black men — who also have a greater risk of vitamin D deficiency — might benefit from additional screening tests before management with a surveillance protocol.

Assessment of vitamin D status at the time of prostate cancer diagnosis would also identify men with insufficient or deficient levels of 25-OH D who might benefit from vitamin D supplementation. authors wrote.

“An open-label trial of 4,000 IU of oral vitamin D3 in men undergoing active surveillance for favorable risk prostate cancer demonstrated a 55% decrease in the number of positive biopsies or Gleason grade at 1 year, with no adverse events among men in the study,” they noted.

Nevertheless, they cautioned that further long-term research is needed to substantiate both screening and supplementation measures.

Michael Holick, MD, of Boston University, who is far more bullish regarding the potential benefits of routine vitamin D screening and supplementation, noted in an email to MedPage Today that deficiency is equally rampant in men and women from Florida to Chicago.

“In men with early prostate cancer, I treat vitamin D deficiency with 50,000 IUs of vitamin D2 or D3 weekly for 8 weeks, and then reduce dosing frequency to every 2 weeks, which is equivalent to ingesting about 2000-3000 IUs daily … you want to achieve a 25-hydroxyvitamin D of at least 30 ng/mL with a preferred range between 40-60 ng/mL,” Holick said.

Stephen Freedland, MD, of Cedars-Sinai Medical Center in Los Angeles, commented that while the study is intriguing, findings from such a small, selected sample (acknowledged by the investigators) do not provide a basis for action at the clinical level in terms of either testing D levels or supplementation. Freedland and Murphy both noted that literature on vitamin D and prostate cancer to date has been mixed, including a 2014 meta-analysis that suggested a negative association between serum D levels and prostate cancer risk.

It is still too early to draw conclusions, Freedland said.

One author reported research funding from GSK. One author holds patents, royalties, and other intellectual property.


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