PSA remains best indicator of prostate cancer progression

Despite recent claims by some urologists that measuring the blood protein prostate-specific antigen (PSA) may not be effective in predicting risk of prostate cancer, a Johns Hopkins study of more than 2,000 men confirms that PSA remains the best measure of the likelihood of cancer recurrence after surgery.

Results of the study, published in the October issue of The Journal of Urology, demonstrated that men with high PSA levels prior to prostate removal surgery were significantly more likely to have advanced clinical stages of cancer, evidence of higher grade cancers in surgically removed tissue, and spread of cancer cells beyond the prostate. In addition, increasing PSA was significantly associated with increased risk of cancer recurrence after surgery, even in men with lower PSA levels prior to surgery.

The study was led by Stephen J. Freedland, M.D., clinical instructor of urology, and Alan W. Partin, M.D., Ph.D., professor and chair of urology at Johns Hopkins’ Brady Urological Institute.

“In our study, PSA levels measured before prostate removal surgery were significantly associated with the risk of recurrent cancer after surgery,” Freedland says. “These data support the notion that PSA remains the best available prostate cancer tumor marker. It certainly suggests that the PSA era is alive and well.”

PSA is a protein produced by cells of the prostate gland. Prostate cancer can increase PSA, so the higher the PSA level, the greater the likelihood that a patient has prostate cancer. Also, higher PSA values generally reflect larger, more aggressive cancers. Freedland acknowledges that because PSA provides physicians with a measure of a patient’s prostate health at a single point in time, it’s “far from perfect.” However, he says, “it’s better than anything else we have.”

“As a screening tool, PSA has done what we wanted it to do,” Freedland says. “It detects advanced disease early and reduces the likelihood of metastatic disease.”

For the study, Freedland and colleagues reviewed patient records for 2,312 men who had prostate removal surgery at Johns Hopkins between 1992 and 2004. All operations were performed by Patrick C. Walsh, M.D., professor and former chair of urology. The research team compared the association between preoperative PSA and the risk of cancer recurrence after surgery.

During an average follow-up of five years, 211 men (10 percent) had signs of recurrent cancer. Higher PSA levels prior to surgery were significantly associated with increased risk of cancer after surgery. Compared to men with PSA levels less than 10 nanograms per milliliter, men with PSA values between 10 and 19.9 nanograms per milliliter were more than three times more likely to develop cancer after surgery. Men with PSA levels of 20 nanograms per milliliter or greater were more than five times more likely to develop cancer after surgery than those with low PSA levels.

Even in men with PSA values of less than 10 nanograms per milliliter, increasing PSA was significantly associated with increased risk of cancer after surgery. For each two-point increase in PSA, the risk of cancer after surgery approximately doubled.

“From our study and others, it is clear that a single PSA value is an extremely useful measure of a patient’s risk of progression after surgery,” Freedland says. “However, looking at how quickly the PSA increases over time is likely to be even more informative than a single value.”