Obesity-Related Plasma Hemodilution and PSA Concentration among Men with Prostate Cancer
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The important association that increased circulating plasma volumes in obese men may hemodilute PSA and result in lower levels is reported in the November 21, 2007 issue of the Journal of the American Medical Association by Dr. Banez and associates. This may result in delayed indications for prostate biopsy and detection of prostate cancer (CaP) in obese men, which could contribute to the explanation that obese men present with more aggressive CaP.
The data analyzed came from the VA SEARCH database along with data from Duke University and Johns Hopkins University. The number of patients from these sites was 1,373, 1,974, and 10,287, respectively. Body mass index (BMI) was categorized as normal (
<25), overweight (25-29.9), mildly obese (30-34.9), and moderately-severely obese (>35). BMI was examined for association with 3 outcomes variables; serum PSA concentration, plasma volume, and PSA mass. The multivariable model adjusted for a variety of clinical and pathological variables. In particular, to study the relationship of BMI and PSA independent of any association between BMI and CaP severity, cancer-specific variables were also adjusted.
The mean BMI was 28.1, 28.1, and 26.9 for the SEARCH, Duke and Johns Hopkins cohorts, respectively. The total obesity category rates were 30% for SEARCH and Duke and 16% for Johns Hopkins. For all three datasets, higher BMI was more likely in younger patients, more likely to be treated in recent years, and more likely to have a positive surgical margin. In the Duke and Hopkins cohorts men with higher BMI had statistically larger prostates. Higher BMI was significantly associated with greater plasma volume in all groups and (for example) men with a BMI of 35 or greater had 21% to 23% larger plasma volumes relative to normal. After adjusting for multiple variables in the analysis, higher BMI was associated with lower preoperative PSA concentrations in all three cohorts. Patients with a BMI >35 had 11-21% lower PSA concentrations relative to normal weight patients.
The association between BMI and PSA mass reflects the total amount of PSA protein in circulation. Only in the Johns Hopkins cohort did PSA mass significantly increase with increasing BMI. The authors determined that this was driven by lower PSA mass in normal weight men and after exclusion of normal weight men there was no significant association.
In summary, obese men had lower PSA values and greater plasma volumes. This data suggests that hemodilution from greater plasma volume may lower PSA values in obese men. Prospective validation is needed but the potential implication is that obese patients may have a delay in CaP diagnosis due to the lower PSA concentrations.
Reference:
JAMA. 298(19):2275-80, November 21, 2007
Bañez LL, Hamilton RJ, Partin AW, Vollmer RT, Sun L, Rodriguez C, Wang Y, Terris MK, Aronson WJ, Jr . Presti JC, KaneCJ, Amling CL, Moul JW, Freedland SJ
Reported by Christopher P. Evans, MD, a Contributing Editor with UroToday.
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