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San Antonio—A study showing that PSA levels appear to have an inverse relationship with body mass index does no harm to the value of the screening test, says Ian M. Thompson, Jr, MD, one of the study's principal authors. Rather, it provides further evidence that PSA cutoffs alone may not best estimate a man's risk of prostate cancer.
Dr. Thompson, Jacques Baillargeon, MD, and their colleagues at the University of Texas Health Science Center in San Antonio, looked at 2,779 men without prostate cancer to find that PSA decreased in a stepwise fashion as body mass increased. PSA levels fell from 1.01 ng/mL in men with normal body weight to 0.69 ng/mL in obese men (p=.0001), a finding that has clinical implications for both primary care physicians and urologists.
The study, an outgrowth of the San Antonio Center of Biomarkers at Risk and sponsored by the Early Detection Research Network of the National Cancer Institute, appears in the March issue of Cancer (published online Jan. 24, 2005).
"Everyone has a different threshold for recommending a biopsy. If a physician sets a threshold of 3.5 ng/mL but the patient has multiple members of his family with prostate cancer, they might lower that to 3.0 or 2.5. Similarly, if a man is morbidly obese, they might want to also lower their threshold and talk to the patient about biopsy. That is one take home-message for urologists. For general practitioners, because of the growing complexity of interpreting PSA in individual patients, it might mean referring a patient to a urologist," he said.
Combine PSA, other variables "The other implication of this study is that PSA as a cancer screening tool is no longer dichotomous," Dr. Thompson added. "It is no longer above 4.0 or below 4.0 ng/mL. Now it is a very complex analysis based upon an understanding of the literature and an understanding of the biology of the cancer-the constitutional makeup of the patient, genetics, diet, body mass index, and other factors. A physician should be able to condense those factors to discuss them with the patient. It behooves the physician who is ordering the PSA to understand that complexity and if he doesn't, perhaps consult with a urologist."
The current study falls on the heels of a 2004 study showing that obesity may be associated with more advanced disease and poorer outcomes (J Clin Oncol 2004; 22:439-45). Some interpreted this finding as suggesting that prostate cancer in obese men may be a more aggressive form of the disease linked to factors such as testosterone or cholesterol. The latest study raises the possibility that obese men have more advanced cancers and worse outcomes because the cancer is being detected later owing to the lower PSA levels, Dr. Thompson said.
The Cancer article and a study published last year in the New England Journal of Medicine (2005; 350:2239-46)showing that up to 25% of men with PSA levels at or below 4.0 ng/mL may have prostate cancer have led some researchers and media outlets to write off the PSA test as a valid screening tool for prostate cancer. Dr. Thompson disagrees.
"PSA is an outstanding marker for prostate cancer," he said. "What we are now suggesting is that we may make it even better by folding in other variables."
Dr. Thompson compared prostate cancer detection to heart disease detection in which clinical findings such as cholesterol levels and diabetes are combined with behavioral factors such as diet, exercise, and smoking to make more accurate diagnoses. The same may be possible for prostate cancer, and large series such as the Prostate Cancer Prevention Trial should enable the acceleration of this process.