Prostate CA recurrence linked with high LDL, impaired fasting glucose

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - Prostate cancer recurrence is not associated with metabolic syndrome but is associated with elevated low-density lipoprotein (LDL) cholesterol and impaired fasting glucose, a new study of U.S. veterans suggests.

"There may not be a simplistic one-to-one association between metabolic syndrome and prostate cancer outcomes, because metabolic syndrome was developed to predict cardiovascular-related risks but involves multiple biochemical pathways. Some of these biochemical pathways are more likely than others to be oncogenic when dysregulated," lead author Dr. Liam C. Macleod, of the University of Washington in Seattle, told Reuters Health by email.

"The study was important to do, given the high number of cases of both prostate cancer and metabolic syndrome," Dr. Macleod said.

As reported online March 31 in Prostate Cancer and Prostatic Diseases, Dr. Macleod and colleagues analyzed data on 705 men treated for localized prostate cancer with radical prostatectomy and another 1,001 treated with radiation. The surgical group was limited to men with undetectable prostate specific antigen (PSA) levels after surgery.

Most of the men were between 55 and 74, white, with a Charlson co-morbidity score of 1 or below, clinical stage T1a-T2a, and Gleason 7 disease and a PSA level below 10 ng/ml at diagnosis.

Over a median follow-up of 41 months (range 1-120), 279 men had recurrence, including 134 (48%) who met criteria for metabolic syndrome.

Elevated LDL cholesterol was associated with PCa recurrence with a multivariable hazard ratio of 1.34 and a propensity-adjusted HR of 1.33. Impaired fasting glucose was also associated with PCa recurrence, with a multivariable HR of 1.54 and a propensity-adjusted HR of 1.41.

There was no association of metabolic syndrome with PCa recurrence.

"The next step is to confirm our results in other cohorts," Dr. Macleod said.

Three experts not involved in the study wrote in emails to Reuters Health that they look forward to future related research.

Dr. Sumanta K. Pal of the City of Hope cancer center in Duarte, California, said the data "are interesting, especially in light of other data (from the same team) suggesting the biological relationship between genes involved in cholesterol synthesis and prostate cancer risk."

The researchers, Dr. Pal said, are well on the way "to defining a plausible mechanism for how prostate cancer may progress beyond initial treatments such as surgery or radiation. This could inform how medical oncologists like myself approach the disease."

Dr. Clayton Stephen Lau, also of the City of Hope, said "subset variables such as elevated LDL and hyperglycemia showed a link to recurrence or prostate cancer after primary therapy. This finding suggests a microenvironment of cholesterol and insulin may exist, promoting the growth of prostate cancer."

And Dr. Richard Wilder of the Moffitt Cancer Center in Tampa, Florida, wrote, "These are provocative findings considering that androgen deprivation therapy is commonly given to intermediate- and high-risk prostate cancer patients treated with radiotherapy and increases fasting glucose levels."

Dr. Wilder said the retrospective findings require longer follow-up, "but they are worthy of study by future investigators."

The National Cancer Institute, the Fred Hutchinson Cancer Research Center, and the VA Puget Sound Health Care system supported this research.

SOURCE: http://bit.ly/1GLfaRk

Prostate Cancer Prostatic Dis 2015.

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