Obesity may be a risk factor for advanced-stage prostate cancer and lower overall survival rates with the disease, but a high body-mass index (BMI) may also be a confounding factor in early diagnosis.
A population-based study of 2,770 men in South Texas has found that mean prostate-specific antigen (PSA) levels of “Class-III” obese men are approximately 30% lower than in men with normal BMIs after adjusting for age and race.
This anomaly could lead to a delay in detection of prostate cancers in overweight men, the researchers believe, and may explain the inferior outcomes in their prostate cancer treatment.
“Lower levels of PSA in obese men could mask biologically consequential prostate carcinomas,” reported researchers at the San Antonio Center of Biomarkers of Risk (SABOR) in a study published in the journal Cancer (posted online on January 24, and due to be published in the March 1 print issue).
SABOR, headed by Ian Thompson, MD, Professor of Urology at the University of Texas Health Science Center at San Antonio, is a clinical and epidemiological center of the National Cancer Institute's Early Detection Research Network.
Had Observed that Overweight Prostate Cancer Patients Had Worse Outcomes
First author Jacques Baillargeon, PhD, Associate Professor of Epidemiology at the University of Texas Health Science Center, said the research was motivated because of the observation that overweight men had worse outcomes after prostate cancer therapy.
“We thought this might be due in part to delayed disease ascertainment,” he said. “Our findings are that this may well be the case.”
A total of 2,850 healthy men without a history of prostate cancer were recruited between March 2001 and 2004 into the SABOR study through San Antonio-area outreach clinics.
The study's ultimate aim is to enroll 10,000 men with the goal of developing new methods of prostate cancer detection using behavioral, genetic, and other markers of disease risk. An effort is being made to oversample ethnic minorities and medically underserved populations.
Subjects give extensive histories and undergo physical exams and blood tests at baseline and annually, and through these exams 71 men were found to have prostate cancer.
For the 2,779 men in the study without prostate cancer who were included in the report, the mean age was 56.7, about 50% were non-Hispanic white, 36.5% were Hispanic, and 12.4% were African-American.
The median PSA level was 1.3 ng/mL, and BMI calculations showed 81.4% of all subjects to be overweight or obese.
BMI was calculated as weight in kilograms divided by height in meters squared—a BMI of 24.9 or less is considered normal or underweight; 25.0 to 29.9 is considered overweight; obese Class I is 30.0 to 34.9; Class II is 35.0 to 39.9; and obese Class III is BMI 40.0 and above.
Dr. Baillargeon reported that mean PSA values decreased in linear fashion with an increase in body-mass index category, from 1.01 ng/mL in normal-weight men, to 0.95 ng/mL in overweight men, to 0.91 ng/mL in Class I obese men, to 0.81 ng/mL in Class II obese men, to 0.69 ng/mL in Class III obese men.
“Both age and BMI exhibited strong linear associations with PSA levels, as PSA increased with increasing age but decreased with increasing BMI,” he said. “And there was a substantial decrease in PSA level that occurred with each increase in BMI category.”
It is intuitive, he continued, that lower circulating levels of androgens and increased levels of estrogens in obese men could affect PSA production due to the androgen response element in the PSA promoter region.
There was no difference between races with regard to the BMI/PSA correlation, Dr. Baillargeon noted.
“Other mechanisms linking obesity with outcomes in men with prostate cancer are increased levels of insulin-like growth factor and estrogens, as well as decreased levels of sex hormone binding globulin.”
A urologic oncologist in private practice in San Antonio said he was not surprised to see the BMI/PSA connection because of what is known about testosterone levels in these men.
“We already understand that testosterone is clearly lowered in obese males—that relationship has been defined for a number of years, so it shouldn't be surprising that their PSA is lower,” said Michael Sarosdy, MD.
“The relationship revealed here between obesity and PSA may simply reflect the already known relationship between obesity and lower testosterone.”
The study's findings are another reflection of the fact that PSA is a very imperfect screening test for prostate cancer, he noted.
“That's why we look at the rate of change of PSA, the relationship of PSA level to volume of prostate, and the relationship between age and PSA.”
The BMI connection is yet another factor urologists need to take into account when considering if a man's PSA is reflective of a healthy prostate or one that may harbor a cancer, he said.
But whether a patient's obesity should lower the threshold for concern about cancer has yet to be determined, Dr. Sarosdy continued.
He said he hoped the SABOR researchers would expand their analysis to include correlations between testosterone, PSA, and BMI.
And in a follow-up interview, Dr. Baillargeon confirmed that, noting that serum samples are available for all the men in the SABOR study and that a continuation of the study to include testosterone in the analysis is being planned.
More Rectal Exams
What is also evident is that more men should be getting annual digital rectal exams in addition to the PSA test, since a man may need a biopsy based on the rectal exam even if the PSA is low, said Michael Sarosdy, MD, a urologic oncologist in private practice in San Antonio.
“Primary care physicians need to get back to doing digital rectal exams. I've noticed in my referral practice that many patients have not had rectal exams, and they are referred to me only because of a high PSA.”
Dr. Sarosdy said this new study, in addition to Dr. Ian Thompson's earlier publication regarding prostate cancer in men with PSA levels under 4.0 ng/mL, emphasizes the need for a rectal exam in a man's annual health assessment.
“Primary care doctors who have gotten away from doing rectal exams need to make note of these facts,” Dr. Sarosdy said, adding that this all points to the need for new biomarkers for use in men with a suspicious rectal exam or high PSA before they are subjected to biopsy.