Association of [-2]proPSA with biopsy reclassification during active surveillance for prostate cancer.

PURPOSE: Previous studies have suggested an association between [-2]proPSA expression and prostate cancer detection. Less is known about the usefulness of this marker in following patients with prostate cancer on active surveillance. Thus, we examined the relationship between [-2]proPSA and biopsy results in men enrolled in an active surveillance program. MATERIALS AND METHODS: In 167 men from our institutional active surveillance program we used Cox proportional hazards models to examine the relationship between [-2]proPSA and annual surveillance biopsy results. The outcome of interest was biopsy reclassification (Gleason score 7 or greater, more than 2 positive biopsy cores or more than 50% involvement of any core with cancer). We also examined the association of biopsy results with total prostate specific antigen, %fPSA, [-2]proPSA/%fPSA and the Beckman Coulter Prostate Health Index phi ([-2]proPSA/free prostate specific antigen) × (total prostate specific antigen)(½)). RESULTS: While on active surveillance (median time from diagnosis 4.3 years), 63 (37.7%) men demonstrated biopsy reclassification based on the previously mentioned criteria, including 28 (16.7%) of whom had reclassification based on Gleason score upgrading (Gleason score 7 or greater). Baseline and longitudinal %fPSA, %[-2]proPSA, [-2]proPSA/%fPSA and phi measurements were significantly associated with biopsy reclassification, and %[-2]proPSA and phi provided the greatest predictive accuracy for high grade cancer. CONCLUSIONS: In men on active surveillance, measures based on [-2]proPSA such as phi appear to provide improved prediction of biopsy reclassification during followup. Additional validation is warranted to determine whether clinically useful thresholds can be defined, and to better characterize the role of %[-2]proPSA and phi in conjunction with other markers in monitoring patients enrolled in active surveillance.

Accuracy of PCA3 measurement in predicting short-term biopsy progression in an active surveillance program.

PURPOSE: PCA3 is a prostate specific noncoding mRNA that is significantly over expressed in prostate cancer tissue. Urinary PCA3 levels have been associated with prostate cancer grade and extent, suggesting a possible role in monitoring patients on active surveillance. We assessed the relationship between PCA3 and prostate biopsy results in men in a surveillance program. MATERIALS AND METHODS: Urine specimens were obtained from 294 men with prostate cancer enrolled in the Johns Hopkins surveillance program. The followup protocol included semiannual free and total prostate specific antigen measurements, digital rectal examination and annual surveillance prostate biopsy. Cox proportional hazards regression was used to evaluate the association between PCA3 results and progression on surveillance biopsy (defined as Gleason pattern 4 or 5, more than 2 positive biopsy cores or more than 50% involvement of any core with cancer). RESULTS: Patients with progression on biopsy (12.9%) had a mean PCA3 score similar to that of those without progression (60.0 vs 50.8, p = 0.131). ROC analysis suggested that PCA3 alone could not be used to identify men with progression on biopsy (AUC 0.589, 95% CI 0.496-0.683, p = 0.076). After adjustment for age and date of diagnosis PCA3 was not significantly associated with progression on biopsy (p = 0.15). CONCLUSIONS: In men with low risk prostate cancer who were carefully selected for surveillance the PCA3 score was not significantly associated with short-term biopsy progression. Further analysis is necessary to assess the usefulness of PCA3 in combination with other biomarkers or in selected subsets of patients undergoing surveillance.