[Diagnostic problems and prognostic factors in prostate cancer]

We aimed to refine the methodology for discriminating ductal (DAP) and acinar adenocarcinomas (AAP) of the prostate preoperatively with a high degree of accuracy, and confirm that prostate carcinoma of ductal origin is a more aggressive subtype. Moreover, we intended to evaluate the clinical utility of transrectal ultrasound-guided systematic sextant or octant biopsies in prediction of extracapsular extension (ECE) at radical prostatectomy. A blinded retrospective analysis of 3-dimensional histology specimens from 110 consecutive radical prostatectomy (RP) cases operated between 2000 and 2006 was carried out (average follow-up: 5.1 years). The samples were also analyzed for 9 different biomarkers. We performed a retrospective analysis of 84 cases of patients who underwent transrectal ultrasound-guided systematic sextant (in 60 cases) or octant (in 24 cases) biopsy. The presence of ECE was correlated to the number of positive biopsies on each side of the prostate by chi-square analysis. Sensitivity, specificity, positive and negative predictive values were calculated for both positive (two or three positive biopsies per side) and negative (no or only one positive biopsy per side) test results. The number of positive cores was thereafter combined with two other parameters: prostate-specific antigen (PSA) and Gleason score. 3-dimensional and conventional histology classified 97 cases of AAP and 13 cases of DAP. DAP cases had a significantly greater frequency of pT3a and more advanced cancers (p<0.0001), >20 mm tumor focus (p=0.0020), highgrade PIN (p=0.0079), Gleason score ≥7 (p<0.0001), positive surgical margin (p=0.0219), ECE (p<0.0001), vascular invasion (p=0.0033), seminal vesicle infiltration (p=0.0213), biochemical/local recurrence (p=0.0015), regional lymph node metastases and distant metastases (p<0.0001). Three biomarkers in combination (chromogranine A, EGFR, p53) distinguished DAP from AAP with an accuracy of 94% (AUC 0.94; 95% CI: 0.88-0.99). ECE was evidenced at RP in 24% (20/84) of the patients. Chi-square analysis demonstrated a significant correlation between the number of positive biopsies and presence of ECE. Analysis of the 168 prostate sides and dominant sides revealed that systematic needle biopsies had a positive predictive value of 46.7% and 37% and a negative predictive value of 89%, and 94%, respectively. Combination of parameters (biopsy Gleason score ≥7 vs. <7, PSA >10 ng/ml vs. ≤10 ng/ml and more than one positive cores vs. 0 or 1 positives) identified patients at high or low risk of ECE, respectively. On the extremes, with only lowrisk parameters none of the 10 patients, while 77% of those with high-risk group had ECE at RP. Both 3-dimensional histology and the three selected biomarkers can accurately distinguish DAP from AAP. This discriminatory ability offers AAP cases less radical treatment regimens and emphasizes the need to develop more effective treatment regimens for DAP cases. The probability of ECE at radical prostatectomy can be accurately predicted based on the number of positive sextant and octant biopsies, solely or in combination with other parameters.