VA Study Finds That Statins Reduce Prostate Cancer Recurrence Risk

by U.S. Medicine

March 31, 2015

By Annette M. Boyle

 CHAPEL HILL, NC – Physicians commonly recommend statins for veterans with high triglyceride levels. Now they may have another reason to encourage these men to take the cholesterol-lowering drugs: Statins appear to lower the risk of prostate cancer recurrence in some patients.cd

“We know that controlling lipid levels is important for cardiovascular disease prevention. Our findings suggest that it may also be important for preventing prostate cancer recurrence in patients with high triglyceride levels,” said Emma Allott, PhD, postdoctoral associate in the department of epidemiology and the Lineberger Comprehensive

Emma Allott, PhD

Emma Allott, PhD

Cancer Center at the University of North Carolina at Chapel Hill, NC. “These patients are already indicated for statins to lower cholesterol. Now we’re seeing multiple benefits that should further encourage them to start therapy.”

Allott and her colleagues found that higher triglyceride levels were associated with increased risk of prostate cancer recurrence in men who had undergone radical prostatectomies, according a study published in Cancer Epidemiology, Biomarkers& Prevention.1

More than 12,000 veterans receiving care through the VA are diagnosed with prostate cancer each year.

“One of the interesting aspects of cancer diagnosis is that it encourages people to adopt new behaviors,” Allott told U.S. Medicine. “We have 12 million prostate cancer survivors in the U.S. now, and the majority will die of heart disease or other causes. Here is additional rationale that they should be doing something about cholesterol, whether that’s lifestyle interventions such as diet and exercise or statin therapy.”

The researchers did not find an association between increased risk of prostate cancer recurrence and total serum cholesterol and low- or high-density lipoproteins (LDL and HDL, respectively) in all men. Triglyceride levels above 150 mg/dl were associated with a 35% increased risk of recurrence, with each 10mg/dl associated with a 2% increase in risk.

In men with abnormally high lipid values, each 10mg/dl increase in total cholesterol above 200mg/dl was associated with a 9% increased risk of recurrence.

The researchers found some good news for men with dyslipidemia, too. Each 10mg/dl increase in HDL levels below the abnormal cutoff of 40 g/dl was associated with a 3% reduced risk of recurrence in these men.

“We’ve known that higher levels of HDL are good for reducing cardiovascular disease risk, but it hasn’t really been established what it does in prostate cancer. Our results are consistent with it being good to increase HDL in men with low HDL,” Allott said.

A previous study had indicated some association between LDL and prostate cancer recurrence, which was not supported by the current research. “It is noteworthy that, although the previous study was limited by sparse LDL data (n=169), more than half of which came from statin users, we had complete LDL data for our entire cohort of 843 men, none of whom were statin users at the time of LDL measurement,” wrote Allott and her colleagues.

The researchers conducted a retrospective cohort analysis of 843 veterans undergoing radical prostatectomy at six VA medical centers from 1999 to 2013 and followed for an average of 74 months. None of the patients studied had taken statins prior to surgery.

“We wanted to capture statin initiation and to assess lipid levels without statins, which are more accurate,” Allott noted.

The authors wrote that the “preoperative lipid levels of statin users may not reflect the environment that their tumors developed in.” By adjusting their models for post-surgical statin use as a time-dependent variable, they were able to assess the association between serum lipid levels and risk of recurrence separately from statin use.

Of the study participants, 325 had cholesterol levels above 200 mg/dl, 263 had elevated triglyceride levels, and 293 had prostate cancer recurrence as indicated by rising PSA levels following surgery.

“Given that 45% of deaths worldwide can be attributed to cardiovascular disease and cancer, with prostate cancer the second most common cause of male cancer deaths, understanding the role of dyslipidemia as a shared, modifiable risk factor for both of these common causes of mortality is of great importance,” the authors noted.

Important for Watchful Waiting

While all the veterans in the study had prostatectomies, the findings could be useful for men who undergo radiation therapy or choose watchful waiting, an option gaining traction within the VA, the authors noted.

In 2009, more than 30% of all veterans diagnosed with prostate cancer and nearly 54% of those with Stage 1 cancer were monitored using watchful waiting. A VA study comparing radical prostatectomy and observation for men diagnosed with prostate cancer following screening found that surgery did not improve survival rates over 12 years of follow-up. 2,3

“Our findings show that high triglyceride levels are associated with increased risk of recurrence, suggesting a role for triglycerides in prostate cancer progression. As such, it may also be important for men choosing watchful waiting to control their triglyceride levels, and future studies are needed to test the association between dyslipidemia and disease progression in this group,” Allott said.

The veterans in the Cancer Epidemiology study had a wide range of cholesterol levels, with 39% exceeding 200 mg/dl. These men had an “interaction with the healthcare system through their prostate cancer diagnosis; maybe they didn’t have much more before. This is a teachable moment. Uncontrolled lipid levels are very common in U.S. males, so prostate cancer diagnosis may be an opportunity to encourage well-established ways to reduce cardiovascular risk as well,” Allott said.

1 Allott EH, Howard LE, Cooperberg MR, Kane CJ, Aronson WJ, Terris MK, Amling CL, Freedland SJ. Serum lipid profile and risk of prostate cancer recurrence: Results from the SEARCH database. Cancer Epidemiol Biomarkers Prev. 2014 Nov; 23(11):2349-56.

2 Maurice M, Zhu H. Persistent Underutilization of Expectant Management for Prostate Cancer Last Decade in The United States. Presented at the American Urological Association Annual Meeting, May 4-8, San Diego, CA.

3 Wilt TJ, Brawer MK, Jones KM, Barry MJ, Aronson WJ, et al. Prostate Cancer Intervention versus Observation Trial (PIVOT) Study Group. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med. 2012 Jul 19; 367(3):203-13.

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