PCA3 Materials & News

Perdonà S, Cavadas V, Di Lorenzo G, Damiano R, Chiappetta G, Del Prete P, Franco R, Azzarito G, Scala S, Arra C, De Sio M, Autorino R. Eur Urol 2010; in press; doi: 10.1016/j.eururo.2010.09.036

• This Italian study in 218 men referred for ≥ 12-core biopsy shows that the Chun nomogram¹ and the Prostate Cancer Prevention Trial (PCPT) risk calculator², both incorporating Prostate Cancer gene 3 (PCA3) and other risk factors such as race, age, family history, prostate specific antigen (PSA) and digital rectal examination (DRE) , can aid in biopsy decisions. This applies particularly for men with PSA levels < 10 ng/mL where biopsy dilemma's occur most often
• This prospective, multicentre Italian study including 218 men referred for a first (61.5%) or repeat (38.5%) ≥ 12-core biopsy because of an abnormal PSA level ≤ 10 ng/mL and/or a suspicious DRE evaluated the performance of the Chun nomogram¹ and the PCPT risk calculator² (both incorporating PCA3)
• The positive biopsy rate was 33.5%, of which 27 were high-grade (Gleason score >=7)
• The median PCA3 Score was significantly higher in men with a positive biopsy (72) vs. those with a negative biopsy (22; P<0.001). Increasing PCA3 Scores correlated with an increasing probability of a positive biopsy (P<0.001)
• The estimated risk of prostate cancer was statistically significantly higher in men with a positive biopsy vs. a negative biopsy when calculated with both the Chun nomogram and the PCPT risk calculator 
• For predicting the outcome of a first biopsy, the Area Under the Receiver Operating Characteristic curve (AUC ROC) was significantly higher for the PCPT risk calculator incorporating PCA3 compared to the Chun nomogram but similar to the PCA3 Score (Table)
• For predicting the outcome of a repeat biopsy the AUC ROCs were comparable for the PCPT risk calculator, Chun nomogram and the PCA3 Score, but significantly better than serum PSA (Table)
• The Chun nomogram displayed better overall calibration (i.e. result of plots of predicted probability of a positive biopsy vs. actual observed proportion of positive biopsy) than the PCPT risk calculator for the entire cohort of men and for the cohort of men with first biopsies. In men undergoing a repeat biopsy, the PCPT risk calculator tended to have a better calibration
• Decision curve analysis was used to estimate the “net benefit” for the nomogram/risk calculator predicting biopsy outcome by summing the benefits (true positives) and subtracting the harms (false positives). The threshold probability at which a man would opt for a prostate biopsy optimally lies between 10-40%. The Chun nomogram had a higher net benefit when the threshold probability was set at <33% compared to the PCPT risk calculator for the entire cohort and for men with a first biopsy. Both risk calculators are superior to the “treat all” strategy of biopsying every man
• If a probability threshold of 25% was used, no high-grade cancers would be missed. At this threshold, the PCPT risk calculator would prevent 11% of biopsies while missing no cancers, and the Chun nomogram would prevent 22% of biopsies while missing 4.1% low-intermediate risk cancers
• It was concluded that both the Chun nomogram and the PCPT calculator, by incorporating PCA3, can aid in the decision to biopsy, especially in men with PSA levels < 10 ng/mL by avoiding unnecessary biopsies without missing significant tumours. The PCPT risk calculator  is available on a website

1. Chun FK, et al. Prostate cancer gene 3 (PCA3): development and internal validation of a novel biopsy nomogram. Eur Urol 2009;56:659-68
2. Ankerst DP, et al. Predicting prostate cancer risk through incorporation of prostate cancer

 More information: Article at PubMed