A more accurate screening test for prostate cancer?

New marker in urine may improve on PSA testing, reduce unnecessary biopsies

Men middle-aged and older routinely get blood tests for prostate-specific antigen, or PSA, to screen for prostate cancer. However, PSA testing has shortcomings: many men with elevated PSAs don’t have prostate cancer and undergo unnecessary biopsies, which can cause infertility, incontinence, and impotence. Other men do have prostate cancer, but have normal PSAs, allowing the cancer to spread undetected. A preliminary study from Children’s Hospital Boston, led by Dr. Bruce Zetter, shows that a simple urine test may improve upon PSA screening. Results appear in the Jan. 21 online edition of the journal Prostate.

Zetter, a researcher in the Vascular Biology Program at Children’s, is interested in the role of cell motility — cells’ ability to move and travel — in helping cancers to metastasize. He became especially interested in thymosin ß15, a protein that stimulates cell migration and promotes metastasis in prostate cancer. Unlike PSA, it is produced almost exclusively by cancer cells, and is detectable in urine.
In this study, Zetter and colleagues compared thymosin ß15 levels in urine samples from 121 men with prostate cancer, 15 men with other genitourinary cancers (kidney or bladder cancer), 81 men with non-malignant prostate disease (such as prostatitis), 73 men with other non-malignant urologic diseases (such as urinary tract infection), and 52 healthy men who served as controls. Thymosin ß15 levels were elevated in men with aggressive or untreated prostate cancer, but normal or near-normal in healthy men and men with other genitourinary diseases. Men with aggressive prostate cancer were 12 times more likely than the healthy controls to have elevated thymosin ß15.

Notably, nearly half of cancer patients whose PSA levels were considered normal tested positive for thymosin ß15. Conversely, many men with other genitourinary diseases had elevated PSAs, but normal thymosin ß15 values. When PSA and thymosin ß15 were combined, the combination detected prostate cancer more often than PSA testing alone, with far fewer false-positives.

Zetter, who is also Children’s Chief Scientific Officer, is now following the long-term outcomes of men with prostate cancer to determine thymosin ß15’s usefulness as a prognostic predictor in combination with PSA testing.

The Vascular Biology Program at Children’s is also actively studying urinary markers for other cancers. In a small pilot study, Dr. Marsha Moses and postdoctoral fellow Dr. Roopali Roy recently found that a compound called ADAM 12, when detected in urine, is an early marker of breast cancer. Another group of markers will soon enter formal clinical trials in adults with prostate, breast, bladder, lung, and colon cancer.