Vitamin D May Boost Survival in Colorectal Cancer Patients

Roxanne Nelson

July 10, 2014

In a study of patients with colorectal cancer, higher levels of vitamin D were associated with better survival than lower levels, and the "magnitude of effect was substantial and clinically important," the researchers report.

However, because all the data so far have come from observational studies, it is too soon to recommend vitamin D supplementation for colorectal cancer patients, according to an expert not involved in the study.

The findings were published online July 7 in the Journal of Clinical Oncology.

When the study participants were divided into tertiles by plasma 25-hydroxyvitamin D (25[OH]D) level, overall mortality was approximately a third lower in the highest tertile than in the lowest.

In addition, disease-specific mortality was 20% at 5 years in the lowest tertile, but "10 years elapsed before mortality reached 20%" in the highest tertile, report Evropi Theodoratou, PhD, Chancellor's Fellow at the Centre for Population Health Sciences, University of Edinburgh, United Kingdom, and colleagues.

For all-cause mortality, the trend was similar; it was 20% at 3.5 years in the lowest tertile and at 6.0 years in the highest tertile.

There were also interactions between 25(OH)D level and vitamin D receptor (VDR) genotypes, which suggest a causal relation between vitamin D and survival.

"We believe that we should more seriously consider the role of vitamin D in colorectal cancer," Dr. Theodoratou told Medscape Medical News. "However, the nature of the relationship between vitamin D and survival after a colorectal cancer diagnosis is not clear, as this was an observational study."

"We can therefore not exclude the possibility that low vitamin D levels were associated with other predictors of poor survival," she cautioned.

Link Already Known, But Gaps in Knowledge

Previous studies have shown a link between vitamin D levels and cancer risk and survival. Some studies have suggested that vitamin D levels are linked to colon cancer risk and an overall improvement in survival for a number of cancer types, including colorectal.

An "umbrella review" Dr. Theodoratou was involved in found that using vitamin D for colorectal cancer prevention, and possibly treatment, is "biologically plausible" (BMJ. 2014;348:g2035), according to David J. Kerr, CBE, MD, DSc, professor of cancer medicine at the Oxford Cancer Centre in the United Kingdom.

"Vitamin D has important effects on cell growth, cell morphology, and cell cytokinetics — a whole range of biological factors that would be relevant and germane to the control of cancer," he explained in a recent Kerr on Oncology Medscape video.

In their umbrella review, Dr. Theodoratou and colleagues note that "despite biological plausibility and a positive trend toward improvements in outcomes, in terms of prevention and in terms of reducing elements of disease recurrence, there were insufficient prospective randomized trials," Dr. Kerr pointed out.

"There is a key gap in the knowledge — the defining evidence, the 'home run' if you like — that we would require to be utterly convinced of the role that vitamin D plays in the prevention and treatment of colorectal cancer," he said.

Lower Mortality with Higher Levels

In the current study, Dr. Theodoratou's team examined the association between plasma 25(OH)D and stage-specific survival in a prospective cohort of 1598 patients with stage I to III colorectal cancer. They also evaluated the interaction of 25(OH)D level with VDR gene locus and VDR polymorphisms (rs1544410, rs10735810, rs7975232, rs11568820), and calculated a protective score for alleles that suppress disease in otherwise susceptible individuals.

In blood samples obtained postoperatively, 25(OH)D level was below 10 ng/mL in 49.7% of patients, indicating deficiency, and was 10 to 16 ng/mL in 26.8% of patients, indicating high risk for deficiency.

In the cohort, 363 deaths were related to colorectal cancer and 168 deaths were related to other causes. Median follow-up was 8.9 years overall, and 9.6 years for those still alive in January 2013.

For colorectal-cancer-specific deaths, median survival was 5.5 years for stage I disease, 3.4 years for stage II disease, and 2.7 years for stage III disease.

For all disease stages, there was a strong association between 25(OH)D level and disease-specific mortality (P = .008) and all-cause mortality (P = .003).

When the highest tertile of 25(OH)D level was compared with the lowest tertile, the adjusted hazard ratio (HR) was 0.68 for disease-specific mortality and 0.70 for all-cause mortality. This effect was particularly apparent in patients with stage II disease, where the adjusted HR was 0.44 for disease-specific mortality, the researchers note.

An interaction was found between 25(OH)D level and the rs11568820 genotype for disease-specific mortality (P = .008), all-cause mortality (P = .022), and protective allele score (P = .004). A trend toward lower rates of cancer mortality was observed for most genotype subgroups.

Too Early for Routine Supplementation

The findings from this study support previous work, said Kimmie Ng, MD, MPH, a medical oncologist at the Dana-Farber Cancer Institute in Boston.

However, it is important to note that this population had extremely low levels of vitamin D, she told Medscape Medical News. "About 50% of patients in the highest category of vitamin D still had levels that would be considered 'deficient' by the Endocrine Society definition."

Nevertheless, the researchers found that having a level above 13.25 ng/mL was associated with significant improvement in cancer-specific and overall survival, compared with having a level below 7.25 ng/mL, she noted.

 
One cannot recommend vitamin D supplements to patients with colon cancer as a treatment option right now.
 

"The findings are encouraging and provide strong rationale for studying vitamin D supplementation in a randomized controlled trial for adjuvant treatment of colon cancer." Dr. Ng said. In fact, her group at Dana-Farber is currently conducting a randomized phase 2 clinical trial of high-dose vitamin D supplementation in combination with chemotherapy for the treatment of patients with metastatic colorectal cancer, she reported.

"However, one cannot recommend vitamin D supplements to patients with colon cancer as a treatment option right now, because all of the data up to this point have been observational," she emphasized. Until data from randomized controlled trials show a definitive survival benefit, "patients should speak with their physicians about whether their vitamin D levels should be checked, and recommendations for supplementation should be made to maintain sufficient levels of vitamin D to promote bone and skeletal health," Dr. Ng said.

The study was supported by grants from Cancer Research UK and the Chief Scientist Office, and by a Cancer Research UK Clinician Scientist Fellowship. The authors have disclosed no relevant financial relationships.

J Clin Oncol. Published online July 7, 2014. Abstract

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