Complexed PSA found to outperform other PSA tests

October 15, 2004

Baltimore--Complexed PSA outperforms total PSA and is as good as or better than percent-free PSA in detecting prostate cancer, according to the results of a large pooled analysis presented at the AUA annual meeting.

Baltimore-Complexed PSA outperforms total PSA and is as good as or better than percent-free PSA in detecting prostate cancer, according to the results of a large pooled analysis presented at the AUA annual meeting.

Among a pooled population of more than 5,000 men, and specifically within a subgroup of men with total PSA of 2.0 to 6.0 ng/mL, complexed PSA had better specificity than both total PSA and percent-free PSA at sensitivity values Ž85%, whereas complexed PSA and percent-free PSA were similarly superior to total PSA among men with total PSA values ranging from 4.0 to 10.0 ng/mL.

"These results may appear to conflict with findings from some previously published studies," said investigator Bruce J. Trock, PhD, director of the division of epidemiology, Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore. "However, this is the largest comparison of these PSA tests to date, and as a large, multicenter investigation pooling data from different populations seen in different practice scenarios, it might provide information that is more applicable to individual urologists who see a broad range of patients in diverse settings.

Sensitivity, specificity compared The investigation included data from eight institutions in the United States, United Kingdom, and Spain collected in six previously published studies. The pooled population consisted of 5,437 men. Of those, 1,944 (36%) subjects had prostate cancer, and 2,955 (54%) were prospectively studied. To account for variability across the different studies, the data were combined using a random effects model.

Using data from the entire population, the four assays offered similar sensitivity (range, 85% to 88%) based on published cutpoints for each test. Complexed PSA had a slightly higher specificity (˜31%) than the other three tests (range, 23% to 26%). However, considering only high fixed sensitivity values (85%, 90%, and 95%), complexed PSA outperformed each of the other tests. For example, at a sensitivity level of 90%, the specificity of complexed PSA was 24.9%, compared with values of 18.6% to 23.2% for the other tests, respectively.

Among 3,388 men with total PSA values in the 4.0 to 10.0 ng/mL range, relative test performance varied by sensitivity level. At a sensitivity of 85%, specificity was higher for complexed-to-total PSA (23.6%) and percent-free PSA (22.8%) compared with both total PSA (15%) and complexed PSA (20.4%). However, at a sensitivity of 90%, the specificity of complexed PSA and percent-free PSA was comparable at 15.5% with complexed-to-total PSA slightly superior (16.6%), whereas complexed PSA outperformed all of the other tests at a sensitivity level of 95%.

"A PSA of 4.0 to 10.0 ng/mL represents the diagnostic gray zone of patients for whom urologists hope an additional test will help them make the decision of whether or not to biopsy. However, comparisons based on sensitivity below 90% are not realistic, as most urologists would not be willing to miss more than 10% of cancers to avoid a small percentage of unnecessary biopsies," Dr. Trock said.

In the analysis of some 2,400 men with a total PSA in the range of 2.0 to 6.0 ng/mL, complexed PSA consistently performed better than the other three tests at sensitivity levels of 85%, 90%, and 95%.

Misleading results? Separately, Dr. Trock presented results from area under the curve (AUC) analyses to show they can be misleading. In this study, the AUC values were dominated by the range of sensitivity below 80%, where percent-free PSA or complexed-to-total PSA perform best. However, at sensitivities of 85% or higher, the curves cross and complexed PSA consistently outperformed the other tests.

"The AUC values do not tell the whole story because the areas where percent-free PSA is superior are at relatively low values of sensitivity, representing a range where clinicians would probably be unlikely to make the trade-off of avoiding unnecessary biopsy and missing a large number of cancers," he said.

The results of this study also showed that, for patients with total PSA in the range of 4.0 to 10.0 ng/mL whose biopsies turned out to be negative, use of either complexed PSA or percent-free PSA to guide the decision to biopsy would have resulted in different populations being spared biopsy. Those who would avoid biopsy on the basis of a complexed PSA <3.4 ng/mL occur primarily in the total PSA range of 4.0 to 5.0 ng/mL. In contrast, use of percent-free PSA >25% would spare biopsy primarily in men with total PSA >5.0 ng/mL.

"These findings suggest that complexed PSA may provide a better decision for biopsy among men with a total PSA <6.0 ng/mL, while percent-free PSA may be more useful for those with a total PSA in the range 6.0-10.0 ng/mL," Dr. Trock said.

Four of the co-authors on this study are investigators for Bayer Diagnostics, including one who is an employee. One co-author is an employee of Immunicon.