The Prostate Cancer gene 3 assay: indications for use in clinical practice

Schilling D, de Reijke T, Tombal B, de la Taille A, Hennenlotter J, Stenzl A. BJU Int 2010;105:452-5

• This review paper discusses five clinical cases in which the PCA3 Assay can be considered, based on scientific evidence and key cases from real-life clinical practice
• Firstly the PCA3 Assay may be used to guide biopsy decisions in men with an elevated prostate specific antigen (PSA) level and one or more prior negative biopsies. European and US studies have shown that the PCA3 Score has a greater diagnostic accuracy than total PSA or %free PSA in predicting repeat biopsy outcome. An increasing PCA3 Score corresponds with an increasing probability of a positive repeat biopsy. The use of the PCA3 Assay in this setting is illustrated by the case of a man aged 47 years old with an increasing PSA level (from about 10 ng/mL to 15 ng/mL) and a normal digital rectal examination (DRE) who had three prior negative biopsies. The high PCA3 Score of 45 indicated an increased probability of a positive repeat biopsy, which was later confirmed
• Secondly, the PCA3 Assay may be used to guide biopsy decisions in men with a family history of prostate cancer and a normal PSA level. Although there is no scientific evidence supporting the use of the assay in this subject population, a clinical case shows that it may be of use. This concerned a man aged 55 years old with a normal PSA level (1.1 ng/mL) and a normal DRE who was concerned about harbouring prostate cancer because of a family history. A high PCA3 Score of 83 indicated an increased probability of a positive biopsy, which was later confirmed
• Thirdly, the PCA3 Assay may be used to guide biopsy decisions in men with an elevated PSA level in whom there is uncertainty as to whether to perform an initial biopsy. A European study showed that the diagnostic accuracy of the PCA3 Assay is statistically significantly better than that of serum total PSA for predicting initial biopsy outcome in men with an elevated PSA level. This can be illustrated by the case of a 67-year old man with a total PSA level of 18.5 ng/mL, a suspicious DRE and a prostate volume of 50 mL. The low PCA3 Score of 11 indicated a low probability of finding prostate cancer in the biopsy and indeed in none of the 13 cores taken for biopsy, cancer was found
• Fourthly, the PCA3 Assay may be used to guide biopsy decisions in men with an elevated PSA level and a concomitant prostate condition. Although scientific evidence is limited, a case of a 72-year old man with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) demonstrates the value of the PCA3 Assay in this setting. This man had a total PSA of 7 ng/mL, a prostate volume of 70 mL, a normal DRE and no prior biopsies. A low PCA3 Score of 9 indicated a low probability of finding prostate cancer in the biopsy. The 21-core biopsy which was later performed according to standard practice in the clinic was indeed negative
• Finally, in men diagnosed with prostate cancer, the PCA3 Assay may aid in the decision whether active therapy is needed or active surveillance is appropriate. Several studies have suggested that the PCA3 Score may be indicative of the aggressiveness of prostate cancer and may therefore be used to select men with clinically insignificant disease who are candidates for active surveillance. An example is the case of 43-year old man who had a PSA level of 2.9 ng/mL. A 6-core biopsy showed one positive core, with a Gleason score of 5. A radical prostatectomy was recommended. However, the PCA3 Score was 5, indicating a decreased probability of significant cancer. In spite of this, a radical prostatectomy was performed because the patient was anxious showing high-grade prostatic intraepithelial neoplasia (HGPIN) in one area of the prostate
• These key patient cases from daily clinical practice and scientific evidence thus show that the PCA3 Score can aid in guiding prostate biopsy decisions and, potentially, in selecting patients with prostate cancer who are candidates for active surveillance

Reviewed by:

Prof. H. van Poppel

Editorial comment:

This nice review paper combines evidence from clinical practice with up-to-date scientific data to show how the PCA3 test can be used your daily management of men with (a suspicion) of prostate cancer. It demonstrates that the PCA3 test can be used to guide the decision whether or not to perform a repeat biopsy, and likely also in guiding initial biopsy decisions in men with a suspicion for prostate cancer. Cases from clinical practice demonstrate that the PCA3 Assay may also be useful to provide additional information on whether or not to perform a biopsy in men with a family history of prostate cancer and men who have a concomitant prostate condition. Increasing scientific evidence suggests that the PCA3 test may also differentiate clinically significant cancer, which needs active therapy, from insignificant cancer, which can be managed with active surveillance. This may have implications for the future management of men with prostate cancer, in that the PCA3 Score may aid in selecting those men suitable for active surveillance.

More information:

http://www.ncbi.nlm.nih.gov/pubmed/19930176?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=4