Why Do Obese Men Have Lower PSA Concentrations?

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Why Do Obese Men Have Lower PSA Concentrations?

Hypotheses include lower androgenic activity or hemodilution caused by larger plasma volumes.

In men with newly diagnosed prostate cancer, obesity is associated with worse oncologic outcomes. A myriad of issues might contribute to this observation, but investigators frequently have pointed to the potential for delayed prostate cancer detection in obese men. Obese men generally have lower prostate-specific antigen (PSA) concentrations than do nonobese men, perhaps because of lower androgenic activity. Investigators from two southeastern U.S. academic centers evaluated an alternative hypothesis: that hemodilution in obese men leads to lower PSA concentrations.

The researchers performed a retrospective analysis of data from men in three health systems who underwent radical prostatectomy between 1988 and 2006. Preoperative body-mass index (BMI) was calculated as weight in kilograms divided by height squared in meters. Estimated plasma volume was calculated as body surface area multiplied by 1.67. PSA mass (total amount of PSA protein in circulation) was calculated as serum PSA concentration multiplied by total plasma volume. Obesity was defined as BMI $≥$ 30 kg/m². Patients were excluded from the analysis if they had node-positive disease; had undergone transurethral resection for diagnosis; or had received chemotherapy, androgen-deprivation therapy, or radiotherapy. Additional patients were excluded if their records did not contain data on prostate weight and BMI. In the three study centers, 1373, 1974, and 10,287 patients were eligible.

Using multivariate linear regression analyses, researchers examined the associations among BMI and three outcome variables: serum PSA concentration, plasma volume, and PSA mass. The analyses were adjusted for a variety of possible confounders, including age, year of surgery, race, prostate weight, PSA concentration and mass, Gleason score, extracapsular extension, and seminal vesicle invasion.

Thirty percent, 28%, and 16% of men were obese in the three cohorts. Men with higher BMIs were younger, more likely to have been treated recently, and more likely to have had positive surgical margins. After controlling for clinicopathologic characteristics, the researchers found that higher BMI was associated significantly with higher plasma volumes and lower PSA concentrations in all cohorts. In two of the three cohorts, PSA mass did not rise significantly with increasing BMI. In the third cohort, higher BMI was associated with increased PSA mass, but only when men with normal BMI (<25) were compared with those in higher categories.

Comment: As the authors note, several issues are at play here. Because no change was seen in PSA mass in association with BMI, hemodilution seems like a more logical explanation than decreased androgenic activity for lower PSA values that are seen in obese men. To date, no evidence shows that prostate cancer screening lengthens survival; however, in the U.S., screening nonetheless is ubiquitous, and artificially low PSA values in obese men might lead to delayed prostate cancer diagnosis. In addition, hemodilution might affect other novel serum markers that are currently being evaluated. Confounding factors, such as the method used to estimate plasma volume, might have influenced these results; the authors emphasize that prospective validation of these observations is required.

— Robert Dreicer, MD, MS, FACP

Published in Journal Watch Oncology and Hematology November 20, 2007