Prostate cancer gene 3 score predicts prostate biopsy outcome in men receiving dutasteride for prevention of prostate cancer: results from the REDUCE trial.

OBJECTIVES: To examine the ability of the urinary prostate cancer gene 3 (PCA3) assay to predict biopsy-detected cancers in men receiving dutasteride in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study cohort. METHODS: Urine and serum samples from 930 men in the active arm were acquired at years 2 and 4 of the biopsy visits. In addition to univariate logistic regression and receiver operating characteristic analysis, multivariate analysis for association with biopsy outcome was performed for PCA3 score in the presence of serum prostate-specific antigen (PSA), age, prostate volume, and family history of prostate cancer. RESULTS: At year 2, the univariate PCA3 score area under the receiver operating characteristic curve (AUC) was 0.668 versus 0.603 for PSA. At year 4, the PCA3 assay significantly predicted the biopsy outcome (AUC 0.628, 95% confidence interval 0.556-0.700), and the PSA level was not predictive (AUC 0.556, 95% confidence interval 0.469-0.642). The year 2 multivariate model yielded an AUC of 0.712. Removing the PCA3 score decreased the AUC to 0.660 (P = .0166 vs the full model). The median PCA3 scores in the dutasteride arm were not different from those in the 1072 men in the placebo arm (16.2 and 17.2 at year 2, P = .1755; and 18.8 and 18.1 at year 4, P = .2340, respectively). However, the PSA values were reduced >50% in the dutasteride arm at both visits (both P < .0001 vs placebo). At a PCA3 score cutoff of 35, the sensitivity and specificity were equivalent between the 2 arms. CONCLUSIONS: In the present study, the PCA3 assay outperformed PSA for cancer detection in men undergoing dutasteride treatment and improved the diagnostic accuracy when combined with the PSA level and other clinical variables. In addition, no adjustment in PCA3 score was needed to yield equivalent clinical performance between the dutasteride and placebo arms. These findings are particularly important in light of the potential role of dutasteride for prostate cancer chemoprevention.

PCA3 molecular urine test for predicting repeat prostate biopsy outcome in populations at risk: validation in the placebo arm of the dutasteride REDUCE trial.

PURPOSE: We determined the performance of PCA3 alone and in the presence of other covariates as an indicator of contemporaneous and future prostate biopsy results in a population with previous negative biopsy and increased serum prostate specific antigen. MATERIALS AND METHODS: Urine PCA3 scores were determined before year 2 and year 4 biopsies from patients in the placebo arm of the REDUCE trial, a prostate cancer risk reduction study evaluating men with moderately increased serum prostate specific antigen results and negative biopsy at baseline. PCA3, serum prostate specific antigen and percent free prostate specific antigen results were correlated with biopsy outcome via univariate logistic regression and ROC analyses. Multivariate logistic regression was also performed including these biomarkers together with prostate volume, age and family history. RESULTS: PCA3 scores were measurable from 1,072 of 1,140 subjects (94% informative rate). PCA3 scores were associated with positive biopsy rate (p <0.0001) and correlated with biopsy Gleason score (p = 0.0017). PCA3 AUC of 0.693 was greater than serum prostate specific antigen (0.612, p = 0.0077 vs PCA3). The multivariate logistic regression model yielded an AUC of 0.753 and exclusion of PCA3 from the model decreased AUC to 0.717 (p = 0.0009). PCA3 at year 2 was a significant predictor of year 4 biopsy outcome (AUC 0.634, p = 0.0002), whereas serum prostate specific antigen and free prostate specific antigen were not predictive (p = 0.3281 and 0.6782, respectively). CONCLUSIONS: PCA3 clinical performance was validated in the largest repeat biopsy study to date. Increased PCA3 scores indicated increased risk of contemporaneous cancers and predicted future biopsy outcomes. Use of PCA3 in combination with serum prostate specific antigen and other risk factors significantly increased diagnostic accuracy.

The role of imaging with (111)In-ibritumomab tiuxetan in the ibritumomab tiuxetan (zevalin) regimen: results from a Zevalin Imaging Registry.

UNLABELLED: The ibritumomab tiuxetan therapeutic regimen consists of a dose of rituximab, 250 mg/m(2), followed by (111)In-ibritumomab tiuxetan, for imaging, on day 1 and a dose of rituximab followed by (90)Y-ibritumomab tiuxetan, for therapy, on day 7, 8, or 9. Treatment with the Food and Drug Administration-approved regimen also requires that scans be performed at 2-24 h and at 48-72 h after the (111)In-ibritumomab tiuxetan, with an optional third scan at 90-120 h, to confirm appropriate biodistribution. In the clinical trials before the approval of the regimen, only 1 patient (of approximately 400) was not treated with (90)Y-ibritumomab tiuxetan after imaging with (111)In-ibritumomab tiuxetan, because of altered biodistribution. The Zevalin Imaging Registry was established by Biogen Idec Inc. to identify cases of potential altered biodistribution and to collect clinical information in cases in which the regimen was not completed after imaging. METHODS: The registry surveyed treating physicians to verify completion of treatment with the ibritumomab tiuxetan therapeutic regimen in patients treated with (111)In-ibritumomab tiuxetan between March 27, 2002, and March 31, 2003. RESULTS: Survey data were collected on 953 of an estimated 1,144-1,192 patients in whom ibritumomab tiuxetan therapy was initiated (case capture rate of 80%-83%). Thirty-eight cases were reported in which a decision not to treat was made after imaging with (111)In-ibritumomab tiuxetan (4.0% of all cases captured); 16 of these were for imaging reasons, and 22 were for medical reasons. Twelve of the 16 imaging cases met the criteria for altered biodistribution (1.3%). Of these 12 cases, 6 (0.6%) were suspected to be true altered biodistribution and 6 appeared to be due to the use of a procedure for radiolabeling (111)In-ibritumomab tiuxetan that differed from that in the prescribing information. All cases of altered biodistribution were seen on the first image (2-24 h) after the administration of (111)In-ibritumomab tiuxetan. The 22 cases in which decisions not to treat were made for medical reasons accounted for 2.3% of the cases. The majority of these cases (19/22) were in patients who had an expected biodistribution but had a rapid change in their clinical condition that precluded treatment. CONCLUSION: The rate of true altered biodistribution was 0.6% in the Zevalin Imaging Registry, which collected treatment decisions based on data from approximately 80% of all patients treated commercially in the first year after drug approval. All cases of altered biodistribution were apparent on the first image, obtained at 2-24 h after the administration of (111)In-ibritumomab tiuxetan.