Introduction

1. No. 003 PCA3 surpasses Best Clinical Judgment in selecting men requiring a repeat prostate biopsy: Application of a RAND Decision Model to the REDUCE Trial Placebo Cohort Aubin SMJ1 , Tombal B2, Andriole GL3, Groskopf J1, Smets L4, Stoevelaar H4 1: Gen-Probe Incorporated, San Diego, CA; 2: UCL, Brussels, Belgium; 3:Barnes-Jewish Hospital, Washington University School of Medicine, St. Louis, Missouri, USA; 4: Ismar Healthcare, Lier, Belgium • Introduction • There is a need to better individualize the decision for repeat prostate biopsy (rBx) to reduce the number of unnecessary rBx while not underdiagnosing aggressive cancer (PCa). • PCA3 is a biomarker that has been shown to predict the probability that a rPBx will be positive and may be indicative of PCa significance [1-5]. • Results • 1) Patient demographics and baseline characteristics • Table 1 - Baseline characteristics of the study population, i.e. men included in the placebo cohort of the REDUCE trial who had complete data for the appropriateness calculations • 2) Trade-off between reduction in rPBx and missed significant PCa • Comparing the different scenerios, application of RAM expert recommendations including PCA3 would have resulted in a greatest reduction in rPBx and fewer Gleason sum ≥ 7 cancers would have been missed. • The number of missed low-grade cancers would have been highest in the scenario using expert opinion including PCA3. • 3) Diagnostic accuracy • The sensitivity, specificity, PPV and NPV of the RAM scenario including PCA3 for detecting Gleason sum ≥ 7 cancer were superior to the scenario without PCA3. • The specificity and PPV of the RAM scenario including PCA3 were better than those of the model with PCA3 only; sensitivity and NPV were comparable. • Aim • Using the RAND/UCLA appropriateness method (RAM), 12 European urologists developed recommendations for the appropriateness of prostate biopsy (PBx) based on PSA, DRE, number of previous negative PBx, prostate volume and life expectancy, with and without PCA3 Assay results [6]. • The aim was to test the ability of the RAM expert recommendations reflecting physician’s best clinical judgement (BCJ) with or without PCA3 to identify men requiring a rPBx in the placebo cohort of the REDUCE study. • Methods • The RAM expert recommendations for rPBx patient selection were applied to men in the placebo cohort of the REDUCE study, with a baseline PSA 2.5-10 ng/mL and scheduled for rPBx after a prior negative one [6]. The 1024 men included in the analysis were those who had a PROGENSA® PCA3 test before the planned 2-year and 4-year rPBx. • The appropriateness of rPBx in the study population was assessed for three scenarios: • Application of the RAM expert recommendations without consideration of PCA3 (RAM without PCA3) • rPBx considered inappropriate in men with a PCA3 Score < 20 (PCA3 only) • Application of the RAM expert recommendations including the PCA3 Score (RAM with PCA3) • Appropriateness outcomes were correlated with the actual rPBx outcome (negative vs. positive; Gleason sum < 7 vs. Gleason sum ≥ 7 when positive) and a trade-off analysis was done, assessing the balance between the number of inappropriate (‘avoidable’) rPBx versus the number of missed Gleason sum < 7 and ≥ 7, respectively. • Performance characteristics were calculated for the different RAM scenarios (with and without inclusion of PCA3) and the scenario with PCA3 alone. aExpert recommendations; brPBx considered inappropriate in men with a PCA3 Score < 20 N: number of patients; PCa: prostate cancer • Conclusions • Results suggest that RAM expert recommendations only are fairly ineffective for selecting patients requiring a rPBx, because the reduction in rPBx rate is moderate and a significant proportion of Gleason sum ≥ 7 PCa is missed. • In the decision to repeat a PBx, the optimal algorithm should include RAM expert recommendations and PCA3 testing. This combination offers the highest reduction in PBx rate while maintaining sensitivity to detect Gleason sum ≥7 cancer. • References • Marks LS, Fradet Y, Deras IL, et al. Urology 2007;69:532-5. • Haese A, de la Taille A, Van Poppel H, et al. Eur Urol 2008;54:1081-8. • Nakanishi H, Groskopf J, Fritsche HA, et al. J Urol 2008;179:1804-9. • Whitman EJ, Groskopf J, Ali A, et al. J Urol 2008;180:1975-8. • Aubin SMJ, Reid J, Sarno MJ, et al. J Urol 2010;184:1947-52. • 6. Tombal B, Ameye F, de la Taille A, et al. World J Urol 2011;doi:10.1007/s00345-011-0721-0. Acknowledgements This study was supported by Gen-Probe. Poster presentation sponsor