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Background: Prediction models need validation to assess their value outside the development setting.Objective: To assess the external validity of the European Randomised study of Screening for Prostate Cancer (ERSPC) Risk Calculator (RC) in a contemporary clinical cohort.Methods: The RC calculates the probability of a positive sextant prostate biopsy (P(posb)) using serum prostate-specific antigen (PSA), results of digital rectal examination, transrectal ultrasound (TRUS) and ultrasound assessed prostate volume. We prospectively validated the RC in 320 biopsied men (55-75 years), with no previous prostate biopsy, included in five Dutch hospitals in 2008-2011. If the P(posb) was >= 20% a biopsy was recommended. The performance of the RC was tested by comparing the observed outcomes to predicted probabilities, using the area under the curve (AUC) and decision curves analyses.Results: Compared to the screening cohort, men in the clinical cohort differed. They had higher PSA levels (median 6.8 versus 4.3 ng/ml, p Conclusions: The ERSPC RC performs well in a Dutch clinical cohort in men with previous PSA tests and contemporary biopsy schemes, and outperforms a PSA and DRE-based approach in the decision to perform a biopsy. (C) 2012 Elsevier Ltd. All rights reserved.

Objectives: The stage and grade shift of currently diagnosed prostate cancer has led to a diminished prognostic power of the Gleason score system. We investigated the predictive value of the amount of high-grade cancer (Gleason growth patterns 4/5) in the biopsy for prostate-specific antigen (PSA) and clinical relapse after radical prostatectomy. Methods: PSA-tested participants (N = 281) of the European Randomized Study of Screening for Prostate Cancer (ERSPC) who underwent radical prostatectomy were analyzed. Besides clinical features, and serum-PSA, histopathologic features as determined in the diagnostic biopsy and matching radical prostatectomy specimen were related to patient outcome. Results: At a median follow-up of 7 yr, 39 (13.9%), 24 (8.5%), and 12 (4.3%) patients had PSA ≥0.1 ng/ml, PSA ≥1.0 ng/ml, and clinical relapse after radical prostatectomy, respectively. Using Cox proportional hazards, PSA level (p = 0.002), length of tumour (p = 0.040), and length of high-grade cancer (p = 0.006) in the biopsy, but not Gleason score, were independent prognostic factors for biochemical relapse (PSA ≥0.1 ng/ml) when assessed as continuous variables. In radical prostatectomies, the proportion of high-grade cancer (p < 0.001) was most predictive of relapse (PSA ≥0.1 ng/ml). For PSA ≥1.0 ng/ml and clinical relapse, the amount of high-grade cancer, both in the biopsy specimen (p = 0.016 and p = 0.004, respectively) and radical prostatectomy specimen (p = 0.002 and p = 0.005, respectively), but not Gleason score, was an independent predictor. Conclusions: In biopsy and radical prostatectomy specimens of surgically treated prostate cancer, the amount of high-grade cancer is superior to the Gleason grading system in predicting patient outcome. We propose that, in addition to the Gleason score, the amount of Gleason growth patterns 4/5 in the biopsy (whether absolute length or proportion) should be mentioned in the pathology report.

Purpose: At low prostate specific antigen (PSA) the indication for prostate biopsy is usually an abnormal digital rectal examination. We evaluate the diagnostic value of PSA, digital rectal examination, transrectal ultrasonography and tumor characteristics at low PSA (0 to 4.0 ng./ml.). We confirm and add to recent evidence that digital rectal examination has a low predictive value and that many significant cancers at this PSA range may be missed. Materials and Methods: From 1994 to 1997 a total of 10,523 participants 54 to 74 years old were randomized to screening in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer. Of the participants 9,211 (87.5%) had PSA less than 4.0 ng./ml., and underwent digital rectal examination and transrectal ultrasonography. Expected rates of prostate cancer detection were calculated using logistic regression analysis. Radical prostatectomy was performed in about half of the 478 men diagnosed with prostate cancer. Tumors were characterized by pT category, Gleason score and cancer volume in 166 processed radical prostatectomy specimens. In 50 of these cases PSA was 0 to 4.0 ng./ml. Results: The positive predictive value of digital rectal examination and transrectal ultrasonography at PSA 0 to 4.0 ng./ml. was only 9.7%. Positive predictive value strongly depended on PSA. Sensitivity was calculated by using estimates of the prevalence of sextant biopsy detectable prostate cancers. Of 760 detectable cancers 478 (67%) were diagnosed irrespective of PSA in men screened with digital rectal examination, transrectal ultrasonography and PSA. Only 127 of 348 detectable prostate cancers (36.5%) were actually diagnosed in men with PSA 2 to 4 mg./ml. The importance of these missed cancers was evaluated with parameters of tumor aggressiveness within PSA ranges. Conclusions: Approximately half of the tumors missed with PSA 0 to 4 ng./ml. had aggressive characteristics (Gleason score 7 or greater, Gleason 4-5 components) and were organ confined. These tumors should be diagnosed and treated according to the present understanding of their natural history. More sensitive and selective screening strategies are needed. Presently a wrong 'window of opportunity' is used for early detection of prostate cancer.

Application of immunohistochemistry to assess the presence of prognostic tissue markers is used widely. The quantitation of these markers may be hampered by a time-related loss of antigenicity in formalin-fixed paraffin- embedded tissue stored on glass slides. Potential loss of immunohistochemical staining intensity was studied on prostatic needle biopsy sections stored for a maximum of 4 years with antibodies against p27(kip1), CD-44s, MIB-1, and androgen receptor (AR). In benign tissue, the positive/total ratio for p27(kip1) was determined, while CD-44s staining intensity was assessed semiquantitatively. For MIB-1 and AR, nuclear staining intensity was assessed using computed image analysis. An exponential and significant decay of immunoreactivity was seen for p27(kip1), CD-44s, MIB-1, and AR, with half- lives of 587 days, 214 days, and 290 days for p27(kip1), MIB-1, and AR, respectively. Immunohistochemical assessment of prognostic tissue markers on stored slides must be considered with care in research and clinical settings.