A Medical Device Daily

Physician scientists at Columbia University Medical Center and New York-Presbyterian Hospital (both New York) said results of a study presented last week at the American Urological Association’s (AUA; Lithicum, Maryland) annual meeting in San Antonio refute recent claims that the era of the prostate-specific antigens (PSA) test is over.

The Columbia/New York-Presbyterian Hospital study included a statistical analysis of those hospitals’ prostate cancer patients who underwent radically retropubic prostatectomy (RRP) with no adjuvant therapy between 1988 and 2003.

Investigators found that, when controlling for cancer stage and grade, according to the Gleason sum and pathologic stage, pre-operative PSA is an accurate predictor of biochemical failure (BCF) – a measure of cancer recurrence defined as PSA 0.2ng/ml – with the same degree of accuracy, regardless of when the RRP was performed.

The scientists said their study follows research presented at the 2004 AUA meeting by Thomas Stamey, MD, of Stanford University (Palo Alto, California), which found that PSA does not correlate with the amount of cancer that recurs following prostatectomy, but instead to prostate size, which led to speculation about the continued predictive powers of PSA.

“Contrary to other recent interpretations, our analysis finds that PSA remains a vital tool for determining risk of recurrence in prostate cancer patients – indeed, the predictive ability of the PSA test does not significantly vary over the last 15 years,” said Mitchell Benson, director of urologic oncology at New York-Presbyterian/Columbia and interim chairman of the department of urology and George F. Cahill professor of urology at Columbia University College of Physicians and Surgeons.

Medical Device Daily reported in September 2004 that Stamey, who nearly two decades ago reported that serum prostate-specific antigen was proportional to stages of prostate cancer that could be determined through a digital rectal exam, had pronounced that, in the words of his study title, “The Prostate-Specific Antigen Era in the U.S. is Over for Prostate Cancer” (MDD, Sept. 22, 2004).

Stamey held that the PSA test had become all but useless as a screening tool for prostate cancer. He was the lead author of the study, which was published in the October issue of the Journal of Urology. Stamey published his original findings in 1987 in the New England Journal of Medicine, which held that increased blood PSA levels could be used to indicate prostate cancer.

According to Stamey’s article in the Journal of Urology, “Serum PSA was related to prostate cancer 20 years ago. In the last five years, serum PSA has only been related to benign prostatic hyperplasia. There is an urgent need for serum markers that reflect the size and grade of this ubiquitous cancer.”

The Columbia/New York-Presbyterian investigators found that, when controlling for cancer stage and grade, there has been no significant change in the impact of PSA in predicting BCF. Researchers controlled for stage and grade because these two variables, with PSA, are used to predict outcome after surgery.

Using a concordance index, the accuracy of PSA in predicting outcome, stratified by time period in which the procedure was performed, are statistically equivalent: .65 for the period 1988-1993, .66 for the period 1994-1998, and .64 for the period 1999-2003.

The hospital scientists said that a “surprise finding” of their study is that prostatectomy is more effective in preventing cancer recurrence today, even when controlling for PSA level.

The scientists said prostate cancer patients who un-dergo radical prostatectomy are less likely to have cancer recurrence than patients 15 years ago, even when controlling for PSA levels.

Using the same data as the first study and controlling for PSA, researchers found that patients who had the procedure in the years 1999-2003 and 1994-1998 were less likely to have cancer recurrence when compared to patients who had the procedure in the years 1988-1993, with hazard ratios of 0.583 and 0.576, respectively. That second study also was presented at the AUA poster session last week.

“It is well known that since the PSA test was first introduced in 1988-1989, patients have presented with an earlier-stage cancer, with lower PSA, which leads to decreased recurrence. Surprisingly, we found that, even after we controlled for this change in initial PSA level, recurrence is still less likely to occur in recent years, compared to earlier years,” said James McKiernan, assistant attending urologist at New York-Presbyterian/Columbia and assistant professor of urology at Columbia University College of Physicians and Surgeons.

Age wasn’t a factor, and the surgery’s ability to get rid of the cancer was not a factor. The specific factors that do account for the change in outcomes have not yet been determined, the study authors said. However, they said they suspect it may involve prostate cancer tumor volume upon initial presentation.