February 24, 2011 — A change in the level of prostate-specific antigen (PSA) — known as PSA velocity — is not a good predictor of prostate cancer. In fact, in the absence of other indications, such as a positive digital rectal exam or a high PSA level, there is no evidence to support prostate biopsy in men with a high PSA velocity, according to a new analysis.
These findings appear to contradict a body of evidence that supports the relation between PSA velocity and prostate cancer, but "this contradiction is more apparent than real," note the authors.
"What we've shown is that changes in PSA are not very important at all," said lead author Andrew Vickers, PhD, associate attending research methodologist in the Department of Epidemiology and Biostatistics at Memorial Sloan-Kettering Cancer Center in New York City. "The take-home message here is that if the patient doesn't have a high PSA to begin with and has a normal clinical exam, there is no reason to do a biopsy, even if the PSA is increasing."
The study was published online February 24 in the Journal of the National Cancer Institute.
On the basis of their results, the authors believe that measuring PSA velocity should not be included in practice guidelines. "Tracking PSA over time may be helpful clinically, if it is integrated with other information," Dr. Vickers told Medscape Medical News. "But calculating PSA velocity and then applying a simplistic algorithm to it — and then to do a biopsy based on that — does more harm than good."
Dr. Vickers pointed out that one of the problems with PSA velocity measurements is that velocity can be calculated a number of ways. "There is no standardized method, and new ways of calculating it are continually being invented," he said.
A sudden rise in PSA is also not usually indicative of cancer, Dr. Vickers explained. "It may be the result of an infection or other benign disease. It doesn't necessarily warrant a biopsy."
Adds Little Info
In an accompanying editorial, Siu-Long Yao, MD, and Grace Lu-Yao, PhD, note that these findings suggest that using PSA velocity "may not provide more information to either physician or patient as we try to come to a decision about interpreting the results of any screening."
PSA velocity measurements also take time to acquire, say the editorialists, who are both from the Cancer Institute of New Jersey–University of Medicine and Dentistry of New Jersey in New Brunswick. "Recognizing that such data add relatively little information may help prevent inappropriate postponement of follow-up in affected patients."
They note that these findings can help physicians refine and focus their clinical approach, "but they also remind us that the use of PSA as a screening tool still leaves much to be desired."
After more than 20 years of using PSA to screen for prostate cancer, it is estimated that approximately 1 million men might have been unnecessarily treated for clinically insignificant prostate cancer, they write. "The shortcomings of PSA testing also remind us that there is still much art to the diagnosis and treatment of prostate cancer."
PSA screening itself has become a controversial topic and, as previously reported by Medscape Medical News, many experts see it as an imperfect tool for screening men for prostate cancer.
Professional organizations also disagree in their screening recommendations. For example, the American Urological Association (AUA) supports PSA screening, but other groups, such as the European Urological Association and the US Preventive Services Task Force, do not recommend population-based screening because of insufficient data on its benefits and harms.
In the current study, the authors point out that guidelines from the National Comprehensive Cancer Network (NCCN) state that men with a high PSA velocity should consider biopsy even if their absolute level of PSA is very low.
The use of PSA velocity is also included in the PSA Best Practice Statement from the AUA, albeit with a disclaimer that questions whether it adds predictive value to PSA alone, they note.
Unnecessary Biopsies
Dr. Vickers and colleagues evaluated the NCCN and AUA guidelines by assessing the positive predictive value of various PSA velocity cut points in a subset of men with a low PSA. The cohort consisted of 5519 men who were in the placebo group of the Prostate Cancer Prevention Trial, in which all participants received an end-of-study biopsy, regardless of clinical indication.
As anticipated, they found a statistical association between PSA velocity and biopsy outcome. But when PSA velocity was added to a multivariate prediction model, adjusted for factors such as age, race, PSA level, and digital rectal exam, the strong associations seen on univariate analyses were reduced.
The authors also found that incorporating PSA velocity into the prediction model led to a very small increase in the area under the curve, from 0.702 to 0.709. The improvements in predictive accuracy were also smaller for the end points of high-grade cancer (Gleason score of 7 or greater) and clinically significant disease.
Thus, the use of PSA velocity added little to the predictive accuracy of high PSA levels or positive digital rectal exams, the researchers conclude. Hence, biopsying men on the basis of PSA velocity, but no other indications, would lead to a substantial increase in additional biopsies.
Implementing PSA velocity as a guideline would be unlikely to improve patient outcomes, the authors conclude, and "we therefore recommend that organizations issuing policy statements related to PSA and prostate cancer detection remove references to PSA velocity."
The study was funded in part by the Prostate Cancer Foundation, the Sidney Kimmel Center for Prostate and Urologic Cancers, the National Cancer Institute, and the National Institutes of Health. Coauthor Hans Lilja, MD, PhD, from Memorial Sloan-Kettering Cancer Center in New York City, holds a patent for free PSA assays.
J Natl Cancer Inst. Published online February 24, 2011.
These findings appear to contradict a body of evidence that supports the relation between PSA velocity and prostate cancer, but "this contradiction is more apparent than real," note the authors.
"What we've shown is that changes in PSA are not very important at all," said lead author Andrew Vickers, PhD, associate attending research methodologist in the Department of Epidemiology and Biostatistics at Memorial Sloan-Kettering Cancer Center in New York City. "The take-home message here is that if the patient doesn't have a high PSA to begin with and has a normal clinical exam, there is no reason to do a biopsy, even if the PSA is increasing."
The study was published online February 24 in the Journal of the National Cancer Institute.
On the basis of their results, the authors believe that measuring PSA velocity should not be included in practice guidelines. "Tracking PSA over time may be helpful clinically, if it is integrated with other information," Dr. Vickers told Medscape Medical News. "But calculating PSA velocity and then applying a simplistic algorithm to it — and then to do a biopsy based on that — does more harm than good."
Dr. Vickers pointed out that one of the problems with PSA velocity measurements is that velocity can be calculated a number of ways. "There is no standardized method, and new ways of calculating it are continually being invented," he said.
A sudden rise in PSA is also not usually indicative of cancer, Dr. Vickers explained. "It may be the result of an infection or other benign disease. It doesn't necessarily warrant a biopsy."
Adds Little Info
In an accompanying editorial, Siu-Long Yao, MD, and Grace Lu-Yao, PhD, note that these findings suggest that using PSA velocity "may not provide more information to either physician or patient as we try to come to a decision about interpreting the results of any screening."
PSA velocity measurements also take time to acquire, say the editorialists, who are both from the Cancer Institute of New Jersey–University of Medicine and Dentistry of New Jersey in New Brunswick. "Recognizing that such data add relatively little information may help prevent inappropriate postponement of follow-up in affected patients."
They note that these findings can help physicians refine and focus their clinical approach, "but they also remind us that the use of PSA as a screening tool still leaves much to be desired."
After more than 20 years of using PSA to screen for prostate cancer, it is estimated that approximately 1 million men might have been unnecessarily treated for clinically insignificant prostate cancer, they write. "The shortcomings of PSA testing also remind us that there is still much art to the diagnosis and treatment of prostate cancer."
PSA screening itself has become a controversial topic and, as previously reported by Medscape Medical News, many experts see it as an imperfect tool for screening men for prostate cancer.
Professional organizations also disagree in their screening recommendations. For example, the American Urological Association (AUA) supports PSA screening, but other groups, such as the European Urological Association and the US Preventive Services Task Force, do not recommend population-based screening because of insufficient data on its benefits and harms.
In the current study, the authors point out that guidelines from the National Comprehensive Cancer Network (NCCN) state that men with a high PSA velocity should consider biopsy even if their absolute level of PSA is very low.
The use of PSA velocity is also included in the PSA Best Practice Statement from the AUA, albeit with a disclaimer that questions whether it adds predictive value to PSA alone, they note.
Unnecessary Biopsies
Dr. Vickers and colleagues evaluated the NCCN and AUA guidelines by assessing the positive predictive value of various PSA velocity cut points in a subset of men with a low PSA. The cohort consisted of 5519 men who were in the placebo group of the Prostate Cancer Prevention Trial, in which all participants received an end-of-study biopsy, regardless of clinical indication.
As anticipated, they found a statistical association between PSA velocity and biopsy outcome. But when PSA velocity was added to a multivariate prediction model, adjusted for factors such as age, race, PSA level, and digital rectal exam, the strong associations seen on univariate analyses were reduced.
The authors also found that incorporating PSA velocity into the prediction model led to a very small increase in the area under the curve, from 0.702 to 0.709. The improvements in predictive accuracy were also smaller for the end points of high-grade cancer (Gleason score of 7 or greater) and clinically significant disease.
Thus, the use of PSA velocity added little to the predictive accuracy of high PSA levels or positive digital rectal exams, the researchers conclude. Hence, biopsying men on the basis of PSA velocity, but no other indications, would lead to a substantial increase in additional biopsies.
Implementing PSA velocity as a guideline would be unlikely to improve patient outcomes, the authors conclude, and "we therefore recommend that organizations issuing policy statements related to PSA and prostate cancer detection remove references to PSA velocity."
The study was funded in part by the Prostate Cancer Foundation, the Sidney Kimmel Center for Prostate and Urologic Cancers, the National Cancer Institute, and the National Institutes of Health. Coauthor Hans Lilja, MD, PhD, from Memorial Sloan-Kettering Cancer Center in New York City, holds a patent for free PSA assays.
J Natl Cancer Inst. Published online February 24, 2011.
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