Editor's Commentary - ProPSA and diagnostic biopsy tissue DNA content combination improves accuracy to predict need for prostate cancer treatment among men enrolled in an active surveillance program

BERKELEY, CA (UroToday.com) - Triggers for intervention in active surveillance (AS) algorithms for low risk prostate cancer (CaP) remain in evolution.

Periodic prostate biopsy to assess tumor grade and volume and PSA doubling time are the most frequently employed. The NCI funds a group of grants in the Early Detection Research Network to further understanding in this area. Dr. Sumit Isharwal and colleagues at Johns Hopkins University evaluated proPSA/%freePSA in combination with prostate biopsy tissue DNA for prediction of unfavorable biopsy conversion in patients on AS. Their findings appear in the online edition of Urology.

The research groups has previously reported that the DNA content of prostate biopsy adjacent tissue (BA) and CaP tissue (CA) and serum [-2]proPSA/%fPSA can predict unfavorable biopsy and conversion to active treatment from AS in men with low risk CaP. ProPSA is a precursor of PSA that is cleaved, and a formula that combines total PSA (tPSA), fPSA, and [-2]proPSA is referred to as the Prostate Health Index (phi). This study investigated phi, phi vs. [-2]proPSA/%fPSA, and their combination with diagnostic biopsy tissue DNA content to predict unfavorable biopsy results and conversion to active treatment among men on an AS protocol. A total of 71 men banked serum and biopsy tissue; 39 had unfavorable biopsy features and 32 had favorable features. Median follow up was 3.72 years.

Serum phi, [-2]proPSA/%fPSA, DNA content in BA tissue area (in excess of optical density), and CA tissue area were significant predictors as continuous variables for unfavorable biopsy conversion. Dichotomized phi, [-2]proPSA/%fPSA, BA excess of OD, and Ca deviation of OD were significant predictors of unfavorable biopsy conversion at the annual prostate biopsy. There was no statistically significant difference between the accuracy of phi and [-2]proPSA/%fPSA for predicting unfavorable biopsy conversion. Phi and [-2]proPSA/%fPSA were highly significantly correlated and as such considered separately for multivariate analysis with BA excess and CA deviation. Both remained significant in the multivariate models and combined with tissue DNA content demonstrated improvement in predictive accuracy to about 70% (c-index 0.6908-0.6884) for unfavorable biopsy conversion.

Isharwal S, Makarov DV, Sokoll LJ, Landis P, Marlow C, Epstein JI, Partin AW, Carter HB, Veltri RW



PubMed Abstract
PMID: 21216447

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