Purpose: Prostate cancer (PC) is the second most common cause of cancer related death in men. A number of key limitations with prostate specific antigen (PSA), currently the standard detection test, has justified evaluation of new biomarkers. We have assessed the diagnostic potential of Engrailed-2 (EN2) protein, a homeodomain-containing transcription factor expressed in PC cell lines and secreted into the urine by PC in men.Experimental Design: EN2 expression in PC cell lines and prostate cancer tissue was determined by semi-quantative RT-PCR and immunohistochemistry. First pass urine [without prior digital rectal examination (DRE)] was collected from men presenting with urinary symptoms (referred to exclude/confirm the presence of prostate cancer) and from controls. EN2 protein was measured by ELISA in urine from men with PC (n ¼ 82) and controls (n ¼ 102).Results: EN2 was expressed and secreted by PC cell lines and PC tissue but not by normal prostate tissue or stroma. The presence of EN2 in urine was highly predictive of PC, with a sensitivity of 66% and a specificity of 88.2%, without requirement for DRE. There was no correlation with PSA levels. These results were confirmed independently by a second academic center.Conclusions: Urinary EN2 is a highly specific and sensitive candidate biomarker of prostate cancer. A larger multicenter study to further evaluate the diagnostic potential of EN2 is justified.

OBJECTIVETo investigate the accuracy and use of body‐coil magnetic resonance imaging (MRI) in the local staging of prostate cancer before radical prostatectomy (RP).PATIENTS AND METHODSFifty‐six patients undergoing RP were staged before surgery using body‐coil MRI; none was denied surgery on the basis of their scan results. All scans were reported before RP by one of three consultant radiologists and afterward by a colleague with a special interest in prostate MRI, unaware of the patients’ clinical details.RESULTSThe overall sensitivity of MRI at detecting extracapsular extension was 50% on general reporting and 72% when reported by the specialist radiologist; the respective specificities were 84% and 86%. Of the 55 patients included in the study, 18 (33%) had extracapsular disease on histological analysis. MRI was most accurate in the 17 patients at high‐risk (prostate‐specific antigen, PSA, >10 ng/mL and Gleason score ≥ 8) and eight at intermediate risk (PSA < 10 ng/mL and Gleason score 7). In the former group with specialist analysis, the sensitivity was 100%, although this decreased to 67% with general reporting. Both gave a specificity of 82%. Intermediate risk disease gave a sensitivity and specificity of 75%, irrespective of reporting method. The ability of MRI to detect extraprostatic tumour in the 30 low‐risk patients (PSA < 10 ng/mL and Gleason score 2–6) was poor; the sensitivity was 25% with general and 50% on specialist review, although both methods gave a specificity of >90%.CONCLUSIONBody‐coil MRI is sensitive and specific for identifying extracapsular extension of prostate cancer in patients with high‐ or intermediate‐risk disease. Patients at low risk frequently have microscopic extension which is not detected. Opinion from a radiologist with a special interest in prostate MRI can increase the reporting accuracy even when unaware of the patients’ clinical details.

INTRODUCTION AND OBJECTIVES: When focal therapy (FT) is performed with sufficient intensity to eradicate cancer, accurate evaluation for the extent of significant cancer (SC) is essential to avoid undertreatment. By D 0 Amico risk category of prostate cancer (PC), we assessed the possibility of underdiagnosis by MRI and biopsy for: 1) extra-prostatic extension (EPE) at the ablation field; and 2) SC left in untreated area. We then verified the applicability of quadrant-based regional FT to intermediate-and high-risk PC, compared with lowrisk PC.METHODS: We enrolled 203 PC patients in clinical stage T2 on digital rectal examination who underwent multiparametric MRI, systematic 14-core biopsy, and radical prostatectomy. MRI interpretation followed the Prostate Imaging Reporting and Data System version 2. Cancer distribution was analyzed using a quadrant basis. Anterior and posterior prostatic quadrants were assessed through 4 anterior/lateral cores and 4 posterior/lateral cores, respectively. Additional MRI-targeted sampling was included in the assessment of Gleason score (GS). SC was defined as a lesion with volume 0.5 mL and/or GS 4+3 and/or EPE. We consider that the absence of EPE is a precondition for FT and that the absence of SC is prerequisite for the untreated area. Each prostate was examined for EPE using MRI, and each quadrant was then assessed for SC using MRI and 4 biopsy cores.RESULTS: In total, 35/109/59 men were classified as low-/ intermediate-/high-risk cases, respectively. In each risk groups, radiological EPE (rEPE) features on MRI were absent in 31/49/21 men (89/45/36% of each group). Among men without rEPE features in each group, EPE was pathologically absent in 30/47/19 men (97/96/90%) (p ¼ 1.00 and 0.56 in intermediate-and high-risk groups, respectively, vs. the low-risk group). In men without rEPE features, SC was absent in 44/55/23 anterior quadrants (71/56/55%) and 46/55/22 posterior quadrants (74/56/52%). Negative predictive values of the combination of MRI and biopsy for SC were 95/96/100% in anterior quadrants (p ¼ 1.00 and 1.00 in intermediate-and high-risk groups, respectively, vs. the low-risk group) and 94/98/89% in posterior quadrants (p ¼ 0.58 and 0.61).CONCLUSIONS: In intermediate-and high-risk PC selected through MRI and biopsy, EPE is absent in 96% and 90% of men, respectively, and SC left in the untreated area is absent in 96-98% and 89-100% of quadrants, respectively, which suggests that FT is an option for intermediate-risk PC as well as low-risk PC. Although carefullyselected high-risk PC might also be a candidate for FT, further study using a larger cohort is needed.

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