Auprich M, Augustin H, Budäus L, Kluth L, Mannweiler S, Shariat SF, Fisch M, Graefen M, Pummer K, Chun FK-H. BJU Int 2011; doi: 10.1111/j.1464-410X.2011.10584.x
- This single-centre study in men undergoing a first (n=48), second (n=40) or third (n=39) repeat biopsy suggests that the performance of prostate cancer (PCa) risk factors to predict repeat biopsy outcome is influenced by the number of previous negative biopsies. PCA3 demonstrated the highest diagnostic accuracy to predict PCa at first repeat biopsy and would have avoided up to 73% of unnecessary first repeat biopsies. %free prostate specific antigen (PSA) performed best at second and third repeat biopsy
- This single-centre study evaluated the performance characteristics of total PSA, %free PSA, PSA velocity and PCA3 at first, second and third repeat biopsy. A total of 127 men ≤ 70 years with 1 or more prior negative biopsies (8-10 cores) but continued suspicion of PCa were included. Continued suspicion of PCa was defined as a suspicious digital rectal examination (DRE) and/or persistent elevated age-specific total PSA level and/or suspicious histology at prior biopsy (i.e. atypical small acinar proliferation [ASAP] and/or ≥ 2 cores with high-grade prostatic intraepithelial neoplasia [HGPIN]). These men underwent either a first, second or third repeat biopsy (12 or 24 cores). Each patient was only included once in the study. The proportion of avoided repeat biopsies was calculated as: [number of false positives for total PSA-number of false positives for %freePSA or PCA3 or PSA velocity]/number of false positives for total PSA
- The overall positive repeat biopsy rate was 35%
- At first repeat biopsy PCa was detected in 19/48 (40%) men. PCA3, %free PSA and age were identified as the only statistically significant PCa risk factors in univariable analysis. The area under the receiver operator characteristics curve (AUC ROC) showed that PCA3 had the highest diagnostic accuracy
(AUC =0.80) for predicting PCa at biopsy when compared to total PSA, %free PSA and PSA velocity. At a sensitivity of 75%, 85% and 95% the use of the PCA3 score would have avoided 73%, 50% and 26% of first repeat biopsies (Table) - At second and third repeat biopsy, PCa was detected in 13/40 (33%) and 12/39 (31%) men, respectively. %free PSA had the highest diagnostic accuracy for detecting PCa at second or third repeat biopsy and would have avoided most biopsies
- It was discussed that the present study was limited in that the sample size was small, ranging from 39-48 men in the three subgroups. Therefore this study should be regarded as “a proof of principle” study. In addition, the significance of PCa was not assessed. Further studies evaluating the effect of the number of previous negative biopsies on PCa risk factors are needed to provide better guidance to patients and physicians when deciding on repeat biopsies
- It was concluded that the number of previous biopsy sessions influences the performance of PCa risk factors in predicting PCa at biopsy. PCA3 demonstrated the highest diagnostic accuracy to predict PCa at first repeat biopsy and would have avoided up to 73% of unnecessary first repeat biopsies. %free PSA performed best at second and third repeat biopsy
| PCA3 Score | Specificity | Biopsies avoided | |
| Sensitivity 75% | 44 | 83% | 73% |
| Sensitivity 85% | 34 | 59% | 50% |
| Sensitivity 95% | 17 | 31% | 26% |
Editorial comment
This single-centre study including men undergoing first (n=48), second (n=40) or third (n=39) repeat biopsy suggests that the performance characteristics of PCa risk factors in predicting biopsy outcome are influenced by the number of previous biopsies. A European multicentre study in 463 men undergoing first (n=331) or second (n=126) repeat biopsy shows that in this cohort PCA3 was more predictive in predicting biopsy outcome than %free PSA1. Moreover, the diagnostic accuracy of PCA3 in predicting biopsy outcome was independent of the number of prior biopsies. The AUC ROC of PCA3 for predicting first and second repeat biopsy outcome were 0.651 and 0.667, respectively. Further large-size, well-designed clinical studies are needed to evaluate the impact of the number of previous negative biopsies on performance characteristics of PCa risk factors in predicting biopsy outcome. These studies should also take into account the significance of PCa, as in clinical practice unnecessary biopsies need to be avoided, but significant cancer should also not be missed.
1. Haese A, et al. Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy. Eur Urol 2008;54:1081-8
More information: Abstract at PubMed