Faculty Bibliography

PURPOSE: Given the limited sensitivity and specificity of prostate-specific antigen (PSA), its widespread use as a screening tool has raised concerns for the overdiagnosis of low-risk and the underdiagnosis of high-grade prostate cancer. To improve early-detection biopsy decisions, the National Cancer Institute conducted a prospective validation trial to assess the diagnostic performance of the prostate cancer antigen 3 (PCA3) urinary assay for the detection of prostate cancer among men screened with PSA. PATIENTS AND METHODS: In all, 859 men (mean age, 62 years) from 11 centers scheduled for a diagnostic prostate biopsy between December 2009 and June 2011 were enrolled. The primary outcomes were to assess whether PCA3 could improve the positive predictive value (PPV) for an initial biopsy (at a score > 60) and the negative predictive value (NPV) for a repeat biopsy (at a score < 20). RESULTS: For the detection of any cancer, PPV was 80% (95% CI, 72% to 86%) in the initial biopsy group, and NPV was 88% (95% CI, 81% to 93%) in the repeat biopsy group. The addition of PCA3 to individual risk estimation models (which included age, race/ethnicity, prior biopsy, PSA, and digital rectal examination) improved the stratification of cancer and of high-grade cancer. CONCLUSION: These data independently support the role of PCA3 in reducing the burden of prostate biopsies among men undergoing a repeat prostate biopsy. For biopsy-naive patients, a high PCA3 score (> 60) significantly increases the probability that an initial prostate biopsy will identify cancer.

OBJECTIVE: To evaluate the agreement in volumes of prostate tumors determined on multiparametric MRI (mpMRI) and histologic assessment, using detailed software-assisted co-registration. MATERIALS AND METHODS: 37 patients who underwent 3T mpMRI (T2WI, DWI/ADC, DCE) were included. A radiologist traced the borders of suspicious lesions on T2WI and ADC and assigned a suspicion score (SS) from 2-5; a uro-pathologist traced borders of tumors on histopathologic photographs. Software was used to co-register MRI and 3D digital reconstructions of RP specimens and compute imaging and histopathologic volumes. Agreement in volumes between MRI and histology was assessed using Bland-Altman plots and stratified by tumor characteristics. RESULTS: Among 50 tumors, mean difference and 95% limits of agreement on MRI relative to histology were -32% (-128% to +65%) on T2WI and -47% (-143% to +49%) on ADC. For all tumor subsets, volume under-estimation was more marked on ADC maps (mean difference ranging from -57% to -16%) than T2WI (mean difference ranging from -45% to +2%). 95% limits of agreement were wide for all comparisons, with lower 95% limit ranging between -77% and -143% across assessments. Volume under-estimation was more marked for tumors with Gleason score >/=7 or MRI SS 4 or 5. CONCLUSION: Volume estimates of PCa using MRI tended to substantially under-estimate histopathologic volumes, with wide variability in extent of under-estimation across cases. These findings have implications for efforts to use MRI to guide risk assessment.