Having high triglycerides after radical prostatectomy raises the risk of cancer recurrence, researchers found.
In a retrospective cohort study, risk of recurrence rose about 3% for every 10 mg/dL increase in triglyceride levels, Stephen J. Freedland, MD, of Duke University, and colleagues reported online in Cancer Epidemiology, Biomarkers and Prevention.
Other lipid parameters — total cholesterol, LDL, and HDL — did not have significant associations with prostate cancer recurrence, except within the subgroup of men with dyslipidemia, where higher total cholesterol levels were associated with an increased risk of recurrence, they reported.
Conversely, higher HDL levels in this subgroup decreased the risk, the researchers said.
“These findings, coupled with evidence that statin use is associated with reduced recurrence risk, suggest that lipid levels should be explored as a modifiable risk factor for prostate cancer recurrence,” they wrote.
Excess weight and obesity have a significant association with development of aggressive prostate cancer and prostate cancer mortality. Given the strong association between obesity and hypercholesterolemia, cholesterol has been postulated as a contributor to prostate cancer progression, the authors noted. Moreover, laboratory studies have suggested that cholesterol fuels prostate cancer growth by multiple signaling pathways.
“Although epidemiologic evidence does not support an association between serum cholesterol levels and risk of total prostate cancer, there is a suggestion that elevated cholesterol may be associated with increased risk of aggressive disease, although not all studies have reported this finding,” said Freedland and co-authors.
The pervasiveness of overweight, obesity, and elevated cholesterol in Western societies has provided a rationale for studies to clarify cholesterol’s association with prostate cancer. To address the issue, Freedland and colleagues queried the Shared Equal Access Regional Cancer Hospital (SEARCH) database to identify prostate cancer patients who had no history of statin use prior to radical prostatectomy during 1999 through 2013.
The search initially identified 2,542 patients who underwent prostatectomy at six Veterans Affairs hospitals in California, North Carolina, and Georgia. Investigators excluded 1,135 men who had a history of statin use prior to surgery, 482 who did not have preoperative lipid values, and 83 others because of various types of missing data, leaving 843 men for inclusion in the analysis.
For purposes of the study, the authors chose cutoff values for normal versus abnormal lipid parameters consistent with the National Cholesterol Education Program Adult Treatment Panel: 200 mg/dL for total cholesterol, 130 mg/dL for LDL, 40 mg/dL for HDL, and 150 mg/dL for triglycerides. Each patient was classified as having normal or abnormal values for each lipid parameter, meaning that a patient might have normal levels of one parameter but abnormal values for others.
The data showed that 325 patients had abnormal cholesterol levels prior to radical prostatectomy. These men were more likely to begin statin treatment after surgery as compared with men who had normal preoperative cholesterol levels (P<0.001). Otherwise, patients with normal or abnormal preoperative lipid values did not differ significantly.
During a median follow-up of 74.4 months, 293 men had biochemical recurrence of prostate cancer. Kaplan-Meier plots showed no significant association between total cholesterol and the risk of recurrence (P=0.334), a finding that was confirmed by multivariable analyses (P≥0.4). Analyses of HDL and LDL yielded similar results for those two lipid parameters.
Elevated triglyceride levels were associated with a 35% increase in the hazard for biochemical recurrence (HR 1.35, 95% CI 1.05-1.74). Given the association of hypertriglyceridemia and diabetes, investigators repeated the analyses after excluding men with diabetes, and a stronger association emerged for elevated triglycerides and biochemical recurrence (HR 1.46, 95% CI 1.10-1.93).
Freedland and colleagues performed more detailed analyses of the relationship of biochemical recurrence to total cholesterol, LDL, and HDL. Preliminary findings suggested an association among men who had abnormal lipid values at baseline. Repeating the analyses only in patients who had abnormal baseline lipid values, the investigators found significant associations with total cholesterol and HDL.
The risk of recurrence increased by 9% (CI 1.01-1.17) with each 10 mg/dL increase in total cholesterol above 200 mg/dL. The risk of recurrence declined by 39% (CI 0.41-0.91) for every 10 mg/dL rise in HDL.
The authors found no significant interactions between abnormal lipid values and postoperative statin use.
“Although the association between obesity and increased risk of prostate cancer recurrence is likely to be multifactorial, these findings suggest that dyslipidemia may be one of the mechanisms underlying this association,” they wrote. “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.”