Interpretation of the Prostate Cancer Gene 3 in Reference to the Individual Clinical Background: Implications for Daily Practice

Abstract

Introduction: The prostate cancer gene 3 (PCA3) urine assay for the diagnosis of prostate cancer was introduced into clinical practice at the end of 2006. We report our experience with the test in a routine clinical setting and discuss the interpretation of the test results in the context of the individual patient history. Material and Methods: We retrospectively reviewed the data of all patients who received PCA3 determination during a visit to our outpatient clinic between January and June 2008. Prostate volume, prostate-specific antigen (PSA) and (in cases where a biopsy was performed) the biopsy results were collected. Results: The PCA3 score was independent of prostate volume and serum PSA. In our study population, 56 men had a negative (<35) and 47 a positive score (≧35). Thirty-two patients were subsequently biopsied, 18 of which were diagnosed with prostate cancer (51%). Patients with a positive biopsy showed significantly higher PCA3 values (p < 0.05). Sensitivity was 94%, specificity was 36% and the negative predictive value was 83%. The area under the curve in the receiver operating characteristics was 0.81 for the PCA3 score and 0.61 for the serum PSA. Conclusion: The PCA3 value correlates with the probability of a positive prostate biopsy. The high negative predictive value can facilitate the decision for or against a prostate biopsy. However, the low specificity and the comparably high costs hamper the routine use for prostate cancer screening purposes. To increase specificity, in daily practice the PCA3 score should be interpreted carefully with reference to the absolute PSA value and clinical history.

PCA3 score and prostate cancer diagnosis at repeated saturation biopsy. Which cut-off: 20 or 35?

“…Setting a PCA3 cut-off at 20 vs 35 would have avoided 22.9% vs 38.1% of biopsies but 3 (9.4%) and 9 cases (28%) of cancer with GS of 6 would have been missed. Despite these interesting reports, PCA3 accuracy (cut-off ≥ 35) at repeated biopsy remains contradictory: sensitivity, specificity, PPV and NPV range between 47 to 76.6% (5), 66.6 to 78.6% (6), 39 to 74% (16) and 62.5 to 87% (17), respectively; in fact, only NPV is satisfactory being > 80% in three of the five studies evaluated (5,6,17,18,19).…”

Biopsy and treatment decisions in the initial management of prostate cancer and the role of PCA3; a systematic analysis of expert opinion

“…In daily practice, the PCA3 Assay is increasingly being used [9][10][11][12]. Since thousands of patients are treated each day, aggregated clinical expertise from physicians using the PCA3 Assay in their daily clinical practice may provide additional valuable information to evidence-based information on how this test can be integrated in current initial management of PCa.…”

“…PSA), may aid in guiding biopsy decisions and reducing the number of unnecessary biopsies [5][6][7][8]. In daily clinical practice, the PCA3 Assay is increasingly being used for this purpose [9][10][11][12].…”

Recommendations from the EGAPP Working Group: does PCA3 testing for the diagnosis and management of prostate cancer improve patient health outcomes?

“…However, 12 additional studies included matched results of PCA3 and the comparators but enrolled men with both initial and repeat biopsies or they did not report biopsy history. 10,11,[35][36][37][38][39][40][41][42][43][44] Most often, the results from these studies were not stratified by biopsy history.…”

“…Fifteen studies [9][10][11]30,32,[34][35][36][37][38][39][40][41][42][43]46 reported AUC estimates for tPSA and PCA3 in the same population. Overall, 13 [9][10][11]30,32,34,35,37,38,[40][41][42]46 of the15 studies found that the AUC of PCA3 was higher than that of tPSA.…”