PCA3 molecular urine assay correlates with prostate cancer tumor volume: implication in selecting candidates for active surveillance

Nakanishi H, Groskopf J, Fritsche HA, Bhadkamkar V, Blase A, Kumar SV, Davis JW, Troncoso P, Rittenhouse H, Babaian RJ. J Urol 2008;179:1804-10

• This study in 96 men who underwent radical prostatectomy shows that the PROGENSA^TM PCA3 Score correlates with total tumour volume and Gleason score in prostatectomy samples.
• The PCA3 Score may be used in clinical practice to select men who have low volume/low grade cancer who are candidates for active surveillance.
• The PCA3 Score statistically significantly correlated with total tumour volume in prostatectomy samples: r = 0.269; P=0.008.
• The mean PCA3 Score was statistically significantly lower in low grade cancer (prostatectomy Gleason score ≤ 6) vs. high grade cancer (prostatectomy Gleason score ≥ 7; P=0.005).
• The mean PCA3 Score was statistically significantly lower in men with low volume (< 0.5 mL)/low grade (Gleason score ≤ 6) cancer than in men with significant cancer (P=0.007; Figure).
• The PCA3 Score was, in comparison to prostate volume, serum total PSA, biopsy Gleason score and percent positive biopsy cores, the best predictor of total tumour volume.

Reviewed by

Prof. J. Schalken

Editorial comment

The use of the PCA3 test as diagnostic tool has now been extensively documented. Clearly, other indications of the test have to be considered. For the potential to aid in a decision for active surveillance a negative test would have to be indicative for tumors with low malignant potential (indolent cancers). Why may the PCA3 test be helpful in this respect? The PCA3 test identifies prostate cancer (PCa) cells in urine. The urine sample collected after a digital rectal examination (DRE) contains a mixture of normal and PCa cells. The PCA3 Score is calculated as the ratio of the concentrations of mRNA PCA3 / mRNA PSA x 1000. The PSA mRNA used in the ratio normalizes for cells of prostatic origin (normal and malignant). One can hypothesize that a high tumor volume combined with an increased potential of PCa cells to invade into the prostate ductal system (increased in high grade cancers) would result in a higher fraction of PCa cells in the urine and thus a higher PCA3 Score. So far this was a hypothesis. The first experimental evidence is now provided by this paper by Nakanishi et al. It was shown that indolent cancers have a significantly lower PCA3 Score. This demonstrates that the test can aid in the decision to propose active surveillance to a patient. In the follow-up of patients managed with active surveillance, the use of non-prostate cancer specific serial serum PSA measurements can often not reassure the decision for active surveillance. The normal variation in serum PSA may trigger anxiety and a premature switch to intervention. It is conceivable that the prostate cancer specific PCA3 test can be used as a more reliable tool to monitor the patients under active surveillance.

More information:

http://www.ncbi.nlm.nih.gov/pubmed/