Use of Systematic Biopsy Results to Predict Pathologic Stage in Patients with Clinically Localized Prostate Cancer: A Preliminary Report

Background : The purpose of this study was to determine the ability of clinical tests to predict advanced pathologic stage (seminal vesicle invasion, pT3c, or pelvic lymph node metastases, pN+).
Methods : T stage, PSA, PSA density, and pathologic features in systematic biopsy specimens were correlated with pathologic stage in 190 consecutive patients with clinically localized (T1-3) prostate cancer detected by systematic needle biopsies and treated with radical prostatectomies.
Results : Thirty-three patients (17%) had an advanced pathologic stage cancer (pT3c or pN+). In logistic regression analysis, the total length of cancer in all biopsy cores ( P < 0.0005), the percent of poorly-differentiated cancer in each specimen (P < 0.021), and serum PSA (P < 0.028) were the only significant predictors of advanced stage. A model was constructed to predict advanced stage: if the PSA was 6 ng/mL and 4 or more biopsy cores were positive and the total length of cancer in all cores was 20 mm and at least 10% of the cancer was poorly-differentiated, then 14 (93%) of 15 patients had an advanced pathologic stage cancer compared to 11% of the remaining 175 patients (P < 0.0005). Conclusion: The pathologic features of cancer in systematic needle biopsy specimens more accurately predicts which patients have advanced stage cancer than standard clinical tests alone.     

Initial Prostate Biopsy: Development and Internal Validation of a Biopsy-specific Nomogram Based on the Prostate Cancer Antigen 3 Assay

Background

Urinary prostate cancer antigen 3 (PCA3) assay in combination with established clinical risk factors improves the identification of men at risk of harboring prostate cancer (PCa) at initial biopsy (IBX).

Objective

To develop and validate internally the first IBX-specific PCA3-based nomogram that allows an individual assessment of a man's risk of harboring any PCa and high-grade PCa (HGPCa).

Design, setting, and participants

Clinical and biopsy data including urinary PCA3 score of 692 referred IBX men at risk of PCa were collected within two prospective multi-institutional studies.

Intervention

IBX (≥10 biopsy cores) with standard risk factor assessment including prebiopsy urinary PCA3 measurement.

Outcome measurements and statistical analysis

PCA3 assay cut-off thresholds were investigated. Regression coefficients of logistic risk factor analyses were used to construct specific sets of PCA3-based nomograms to predict any PCa and HGPCa at IBX. Accuracy estimates for the presence of any PCa and HGPCa were quantified using area under the curve of the receiver operator characteristic analysis and compared with a clinical model. Bootstrap resamples were used for internal validation. Decision curve analyses quantified the clinical net benefit related to the novel PCA3-based IBX nomogram versus the clinical model.

Results and limitations

Any PCa and HGPCa were diagnosed in 46% (n = 318) and 20% (n = 137), respectively. Age, prostate-specific antigen, digital rectal examination, prostate volume, and PCA3 were independent predictors of PCa at IBX (all p < 0.001). The PCA3-based IBX nomograms significantly outperformed the clinical models without PCA3 (all p < 0.001). Accuracy was increased by 4.5–7.1% related to PCA3 inclusion. When applying nomogram-derived PCa probability thresholds ≤30%, only a few patients with HGPCa (≤2%) will be missed while avoiding up to 55% of unnecessary biopsies. External validation of the PCA3-based IBX-specific nomogram is warranted.

Conclusions

The internally validated PCA3-based IBX-specific nomogram outperforms a clinical prediction model without PCA3 for the prediction of any PCa, leading to the avoidance of unnecessary biopsies while missing only a few cases of HGPCa. Our findings support the concepts of a combination of novel markers with established clinical risk factors and the superiority of decision tools that are specific to a clinical scenario.