Publication
Hessels D, Schalken JA. Nat Rev Urol 2009;6:255-61
- This review paper describes the development of the Prostate CAncer gene 3 (PCA3) Assay from the research laboratory to clinical practice
- In 1999, the PCA3 gene was identified. Studies showed that it was highly over-expressed in prostate tumours compared to normal prostate tissue. This suggested its potential use as a biomarker for prostate cancer
- A method was developed to easily and rapidly quantify PCA3 mRNA levels in urine, i.e. the transcription-mediated amplification (TMA)-based PCA3 Assay. The ProgensaTM TMA-based PCA3 Assay is the first RNA-based molecular diagnostic assay in body fluids for prostate cancer available for urologists. It measures PCA3 and PSA mRNA concentrations in urine, and the PCA3 Score is calculated as [PCA3 mRNA]/[PSA mRNA] * 1,000
- The PCA3 Assay is very robust. Post-digital rectal examination (DRE) urine specimens provide informative rates of > 95%. Moreover, the performance of the Assay varies little within and between research sites
- Unlike serum prostate specific antigen (PSA), PCA3 is prostate cancer specific and not affected by prostate volume / benign prostatic hyperplasia (BPH) or other non-cancerous prostate conditions such as prostatitis
- Several clinical studies have shown that the PCA3 Score correlates with the outcome of a (repeat) prostate biopsy, with a higher PCA3 Score indicating a higher probability of a positive biopsy. In addition, in men undergoing a repeat biopsy, the diagnostic accuracy of the PCA3 Score in predicting biopsy outcome is superior to either serum total PSA or % free PSA. PCA3 Scores have shown to be independent of prostate size, PSA level and number of prior biopsies
- Combining PCA3 with other risk factors for prostate cancer (e.g. serum PSA level, DRE outcome, age, family history of prostate cancer) increases the diagnostic accuracy of multivariate models and risk calculators. This may improve future prostate cancer detection
- The PCA3 Score may be associated with significance of prostate cancer and as such identify men who have clinically insignificant cancer who are candidates for active surveillance. However, as the scientific evidence is still limited further studies are needed
- In clinical practice, the PCA3 Assay may aid in the decision whether an immediate repeat biopsy is needed or can be delayed (Table). In men in whom prostate cancer has been detected, the PCA3 Assay may aid in the decision whether active therapy is needed or active surveillance is appropriate (Table)
- Further studies should evaluate the most appropriate PCA3 Score cut-off for clinical practice and if the PCA3 Score might be useful as a continuous variable in combination with other clinical and/or pathological factors
Table: The PCA3 Assay: the way it can aid in clinical decisions
| Outcome biopsy | PCA3 Score | Established prognostic factor | Course of action |
| Negative | Low | PSA kinetics | Conservative follow-up |
| Negative | High | PSA kinetics | Advanced imaging; repeat biopsy depending on imaging results |
| Positive | Low | Clinical stage and grade; PSA kinetics | Consider active surveillance |
| Positive | High | Clinical stage and grade | Active therapy (e.g. radical prostatectomy, radiotherapy |
More information: Article at PubMed