Haese et al. have just published data from a prospective, multicenter study of the PROGENSA PCA3 assay as a test for prostate cancer in patients having a repeat biopsy (after one or two prior, negative biopsies). Their conclusion states that, “The probability of a positive repeat biopsy increases with rising PCA3 scores. The PCA3 score was superior to %fPSA for predicting repeat prostate biopsy outcome and may be indicative of clinical stage and significance of pCa.” This is probably not the ringing endorsement of the value of the PCA3 test that some people were hoping for.
The prostate cancer gene 3 (PCA3) assay has previously shown considerable potential as an aid in the evaluation and diagnosis of prostate cancer in men with a high probability of a positive (repeat) biopsy. Haese et al.’s study was designed to evaluate the clinical utility of the PROGENSA PCA3 assay, presumably as a pivotal trial of this assay potentially leading to European approval of this test.
The trial was a European, prospective, multicenter study that enrolled men with a history of one or two prior negative biopsies who were scheduled for repeat biopsy. After a digital rectal examination (DRE), first-catch urine was collected to measure the concentration of messenger RNA (mRNA) derived from the PCA3 gene and to calculate the PCA3 score. The PCA3 score was compared to the result of the biopsy for each patient. The diagnostic accuracy of the PCA3 assay was also compared to the percentage of free (not total) prostate-specific antigen.
The results of the study were as follows:
- Among the 463 men initially enrolled, the positive repeat biopsy rate was 28 percent.
- The higher the PCA3 score, the greater was the probability of a positive repeat biopsy.
- The PCA3 score (cut-off of 35) had a greater diagnostic accuracy than the percentage of free PSA (cut-off of 25 percent).
- The PCA3 score was independent of the number of previous biopsies, age, prostate volume, and total PSA level.
- The comparative PCA3 score was significantly higher in men with
- high-grade prostate intraepithelial neoplasia (HGPIN) vs. those without HGPIN
- clinical stage T2 vs. T1
- Gleason score ≥7 versus <7, and
- clinically “significant” versus “indolent” disease
(In the last bullet point above, clinically “indolent” disease was defined as clinical stage T1c, PSA density <0.15 ng/mL, Gleason score on biopsy ≤ 6, and percent positive cores ≤ 33 percent.)
It would seem to The “New” Prostate Cancer InfoLink that there may need to be additional work done to clearly demonstrate the precise clinical value of the PCA3 assay before this test is ready for “prime time.” While it is encouraging that there was a consistent association between known higher as opposed to lower risk factors, our primary concern would be the degree of selectivity and specificity of this test in making decisions that affect individual patients (particularly with respect to false positive and false negative rates).
Filed under: Diagnosis
Although not mentioned here, I understand that in calculating the PCA3 value, reference is made to the PSA test number. Given the inherent inaccuracy of that test and the wide range of results, surely the application of additional calculations would result in a less accurate value — or at least a wide range?
The rumor mill tells me that at least one of the major prostate cancer reference laboratories is entirely less than impressed by the potential value of the PCA3 test for all sorts of reasons. This would indeed, probably, be one of them.