Study Indicates PSA Velocity Measurement Improve Detection of Prostate Cancer – But it may not be Relied Upon

January 18, 2013 by  
Filed under Prostate Cancer News

A study published online January 15 in BJU International reveals that repeated measurements of prostate specific antigen (PSA) may likely improve detection of prostate cancer, which may include the aggressive form of the disease.

However, there are some experts which believe the above study cannot be relied upon because the PSA test is not a good predictor of cancer of the prostate. Here are highlights on the details about this study:

Repeated measurements of prostate-specific antigen (PSA) improve the detection of prostate cancer, compared with a single measurement, according to a study published online January 15 in BJU International.

Furthermore, multiple test results, which document PSA changes over time and are known as PSA velocity, improve the accuracy of predicting aggressive disease, say the authors, headed by Lauren P. Wallner, PhD, MPH, a fellow at Kaiser Permanente Southern California, a managed care organization.

But an expert on this issue disagrees. PSA velocity is not a predictor of either prostate cancer or aggressive disease, Andrew Vickers, PhD, from the Memorial Sloan-Kettering Cancer Center in New York City, told Medscape Medical News.

Dr. Vickers, who was not involved in this study, has been involved in 4 large studies that show that PSA velocity does not improve detection beyond the use of PSA alone.

In their study, Dr. Wallner and her colleagues retrospectively examined the electronic health records of nearly 220,000 men 45 years and older over a 10-year period who had at least 1 PSA measurement and no previous diagnosis of prostate cancer. On average, the men received approximately 5 PSA tests during the study period.

In the study cohort, the average change in PSA level per year was 2.9%; the rate of change increased modestly with age (P = .001).

PSA velocity only “somewhat” improved the prediction of prostate cancer, compared with a single measure, but PSA velocity is nonetheless valuable, especially for predicting aggressive disease, say the study authors.

“The results of this study could provide clinicians with a better prostate cancer preventive strategy that could help differentiate between men with an aggressive form of the disease and those who have slow-growing, indolent cancer that may not necessarily merit treatment,” Dr. Wallner said in a press statement.

However, Dr. Vickers says that the study methodology is fundamentally flawed and the results are a “self-fulfilling prophecy.”

Furthermore, the research Dr. Vickers was involved in suggests that PSA velocity is not more clinically valuable than a single PSA test.

In the discussion section of their paper, Dr. Wallner and colleagues acknowledge these findings from the Vickers-led studies.

In 4 studies led by Dr. Vickers, PSA velocity did not improve the prediction of prostate biopsy outcomes and did not improve detection beyond the use of PSA alone. In 2 of the studies, PSA velocity did not improve the detection of aggressive prostate cancers.

But Dr. Wallner and her colleagues say their own results, as well as the results of some others, contradict those findings.

Inflated Results?

Dr. Vickers notes that a major flaw in the study lies within the diagnosis of prostate cancer in the men who were studied.

The men who went on to be diagnosed with incident prostate cancer were identified through the Kaiser Permanente Southern California Cancer Registry. The baseline patient characteristics in the men who developed prostate cancer were then compared with those in the men who did not.

This is a big problem, Dr. Vickers explains. “In the study, there are men who were not diagnosed with prostate cancer. But [Dr. Wallner and colleagues] don’t know if these men actually did not have prostate cancer.”

In other words, because not all of the men were biopsied, there is no way to determine definitively who in the study population had prostate cancer and who did not.

“In studies with universal biopsy, there is no value in PSA velocity,” Dr. Vickers told Medscape Medical News in an interview.

The authors acknowledge that it is not fully knowable which men had prostate cancer and which did not. “Verification bias resulting from the presence of subclinical prostate cancer among men defined as disease free cannot be ruled out. This differential misclassification could result in inflated estimates of the sensitivity and underestimates of the specificity,” the write.

In other words, they admit that their results could be inflated.

The results are inflated, Dr. Vickers asserts. He points to the findings on the area under the receiver operator characteristic curves (AUC) to illustrate this point.

For prostate cancer overall and for aggressive disease (Gleason score of 7 or higher), the accuracy of PSA velocity in predicting prostate cancer was compared with that of a single measure of PSA level using the AUC. AUC estimates ranged from 0.5 (equal to chance) to 1.0 (perfect accuracy).

Dr. Wallner and colleagues report that PSA velocity marginally improved the prediction of prostate cancer overall, compared with a single measure (AUC, 0.963 vs 0.944), but more accurately predicted aggressive disease (AUC, 0.955 vs 0.727).

Dr. Vickers pointed out that 0.6 is roughly the AUC number needed to predict prostate cancer. Remarkably, the 0.95 result for aggressive disease “suggests that PSA velocity is almost a perfect predictor,” he scoffed.

But there is no such thing as a perfect predictor of prostate cancer, said Dr. Vickers. Thus, these findings about PSA velocity are grossly exaggerated and not valuable, he explained.

Indeed, predicting prostate cancer with PSA testing is so imperfect that the US Preventive Services Task Force recommends against PSA-based screening for asymptomatic men.

Kaiser Permanente guidelines include a recommendation that men 40 years and older discuss the PSA test and rectal exam with their physician, according to a press statement from the organization. Source.

Conclusively, this research is revealing for the use of PSA velocity measurement for testing prostate cancer.

Dr. Vickers and others in his school of thought should not be ignored as there is no yet a perfect predictor of prostate cancer.

While the PSA velocity will marginally improve the prediction of prostate cancer overall, the accuracy of this test in many people is still of much importance.

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