Dec 29, 2014
By Shira Klapper, Senior Writer/Editor
Researchers and oncologists in the field of genitourinary cancer continue to debate the value of using the prostate-specific antigen (PSA) test to detect prostate cancer. Among the criticism of the PSA test is that it has a high false-positive rate, meaning that many men who report an elevated PSA score are recommended for biopsy, but are ultimately found not to have cancer. The issue is that biopsy can come with risks of its own, for example, it is invasive, and may cause bleeding and sepsis. These risks have prompted research on additional biomarkers that could supplement the information from the PSA and thus provide a better indication about prostate cancer risk—specifically, whether the risk is high enough to warrant a biopsy or low enough to forego the procedure.
Now a study in the Journal of Clinical Oncology (JCO), “Can Urinary PCA3 Supplement PSA in the Early Detection of Prostate Cancer?” validates the use of one such supplemental biomarker: prostate cancer antigen 3 (PCA3). The study, published online, ahead of print, November 10, 2014, found that when the score from the urinary PCA3 biomarker was considered alongside the PSA score, it resulted in a more refined measurement of risk for than could be provided with PSA alone, for both general cancer and high-grade cancer. PCA3 is a gene that is overexpressed in prostate cancer.
The study’s first author, John T. Wei, MD, MS, explained how PCA3 differs from other biomarkers that serve as supplements for PSA. “PCA3 is very important because it is the first in class,” said Dr. Wei. “All of our other biomarkers up until this point that have been commercially available are really versions of PSA and derivatives of PSA. Since PCA3 is not PSA-based, it’s more likely to give you information that has less overlap with PSA information. And this is what we saw in this study.”
Fine-tuning the risk
As part of the study, which was funded by the National Cancer Institute (NCI) and was carried out across 11 centers, the PCA3 test was given to 859 men who had an elevated PSA score and were therefore recommended for biopsy. For purposes of analysis, these men were divided into two groups: those who had received a biopsy in the past and those who were about to undergo their first biopsy. After the biopsy results came in, the researchers asked: Did adding the PCA3 results to the PSA scores lead to more accurate predictions about who had a low-enough risk to be able to forego a biopsy and who had a high enough risk that biopsy would be indicated? The answer was yes.
Dr. Wei described the study’s most important findings. “For men who never had a biopsy and who had an elevated PSA, our study found that if they had a PCA3 cut-off of 60, their risk of having prostate cancer was high enough that they should have a biopsy. For men who've had a biopsy before and now their PSA is still elevated, if they have a PCA3 score of less than 20, according to this study’s findings, they can wait on the biopsy so long as they continue to have their cancer risk monitored.”
An equation for predicting risk
Based on the information gathered in the study, the researchers generated a table that allows doctors and patients to see the magnitude of risk for prostate cancer in general and for high-grade cancer specifically based on patients’ PCA3 and PSA scores.
“We wanted the PCA3 test to be immediately helpful, which is why we added a risk-estimation table,” said Dr. Wei. “Clinicians can use the information in the table to talk to patients and help them decide whether to proceed with a biopsy.”
John T. Wei, MD, MS is a General Urologist and a Professor of Urology at the University of Michigan, in Ann Arbor.
Read the abstract of the original JCO article.
View the PDF of the original JCO article.
Wei JT, Feng Z, Partin AW, et al. Can urinary PCA3 supplement PSA in the early detection of prostate cancer? J Clin Oncol. Epub 2014 Nov 10.
The Exclusive Coverage series on ASCO.org highlights selected research from JCO and JOP with additional perspective provided by the lead or corresponding author.
@ 2014 American Society of Clinical Oncology