Atypical Small Acinar Proliferation Research Articles

前立腺生検による前立腺炎後に発症した急性一側性外転神経麻痺の1例

This is a case of repeated acute abducens nerve palsy following prostatitis due to prostate biopsy. A 64-year-old man came to our hospital because of high prostate specific antigen (PSA; 25 ng/ml) on routine medical examination. Transrectal prostate needle biopsy revealed atypical small acinar proliferations in two cores taken from the apex of the prostate. One day after biopsy, the patient presented with chills and a fever. Prostatitis due to prostate biopsy was diagnosed, and hydration and intravenous antibiotics were administered. Although he showed signs of improvement, seven days after biopsy, he complained of double vision in the left gaze. Upon referral to the neurology, head MRI and CSF examination showed no particular abnormality. He was thus diagnosed with post-infection abducens nerve palsy and treated with steroid therapy. His symptoms gradually ameliorated. One year after biopsy, his PSA level was still high, although follow-up prostate biopsy was benign. One day after follow-up biopsy, he presented again with chills and a fever. He was retreated with hydration and intravenous antibiotics. Six days after follow-up biopsy, he complained of double vision in the left gaze as in the previous year. With the diagnosis of post-infection abducens nerve palsy, he was retreated with steroid therapy.

A Novel Repeat Biopsy Nomogram Based on Three-dimensional Extended Biopsy

To develop a nomogram based on a cohort examined with 3-dimensional (3D) protocol for diagnosis of prostate cancer on repeat biopsy. Of 4074 consecutive men undergoing prostate biopsy at our institutions between 2000 and 2009, 775 men with at least 1 previous negative biopsy underwent repeat biopsy with a 3D protocol. Men with previous atypical glands or atypical small acinar proliferation and/or without available prostate-specific antigen (PSA) kinetics information were excluded. The remaining 515 men constituted the study cohort. We developed a logistic regression-based nomogram with 70% of the cohort selected randomly; we validated it with the remaining 30%. Predictive accuracy and performance characteristics were assessed using the area under the receiver operating characteristic curve (AUC) and calibration plots, respectively. The threshold probability was evaluated with decision curve analysis. We developed a novel repeat biopsy nomogram incorporating age, free to total PSA ratio, prostate volume, history of previous extended biopsy, and PSA doubling time. Validation confirmed predictive accuracy with an AUC value of 0.791. Calibration plots showed good agreement. The decision curve of the nomogram was superior to the decision curve of biopsying all men in a range of threshold probability over 0.15. At the threshold of 0.2, the number of unnecessary biopsies could be reduced by 10 per 100, without missing prostate cancer. We developed a novel repeat biopsy nomogram based on a cohort examined with 3D protocol. This repeat biopsy nomogram is clinically beneficial, preventing a substantial number of unnecessary biopsies.

Premalignant and Malignant Prostate Lesions: Pathologic Review

High-grade prostatic intraepithelial neoplasia (HGPIN) is currently the only recognized premalignant lesion of prostatic carcinoma. This review article discusses HGPIN, its link to prostatic adenocarcinoma, and the significance of its presence on needle biopsy. The criteria and clinical impact of the diagnosis of atypical small acinar proliferation on needle biopsy are reviewed. Certain subtypes of prostate cancer that are not associated with HGPIN are of clinical relevance, and the unique clinicopathologic features of these subtypes are discussed. Histologic variants of prostatic adenocarcinoma with distinct cell types are also described. HGPIN is the only known pathologic factor currently available to distinguish which patients may be at risk for detecting carcinoma on repeat biopsy. Histologic variants are recognized due to the inference of a particular Gleason grade pattern associated with the cell type, hence affecting prognosis. Typically, pure forms of these histologic variants are associated with worse prognosis due to the associated high Gleason grades. HGPIN has a strong association with acinar-type prostatic adenocarcinoma. HGPIN and acinar-type prostatic adenocarcinoma both show similar molecular alterations, providing further evidence of their association.

Which Factors allow to Anticipate the Diagnosis of Prostate Cancer in Pin Patients? A Study on 546 Patients

Aim of the study TO analyze which factors allow to assess the risk of finding a prostate cancer (PCa) at repeated biopsies in patients with diagnosis of prostatic intraepithelial neoplasia (PIN). Patients and Methods At our institute all patients with a diagnosis of PIN undergo a 6–monthly control biopsy until the achievement of a benign histology or up to a maximum of 4 consecutive biopsies. For this study a retrospective review of clinical and bioptic data of patients with a diagnosis of isolated PIN (i.e. without associated atypical small acinar proliferation or small cancer foci) was carried out. The correlation between these features and the probability to find PCa at the first re-biopsy or at a further re-biopsy was independently analyzed. Results The data of 546 patients subjected to a median number of 3 biopsies, (mean: 10.8 and 12.9 cores at initial biopsy and at first re-biopsy respectively), and with a mean “bioptic” follow-up time of 14.8 months, were analyzed. PCa was found in 174 cases (31.8%): for 116 of them it took place at the first re-biopsy with a mean latency of 7.8 months from PIN diagnosis, whereas for 58 at a further re-biopsy with a mean latency of 21.6 months. The risk of diagnosing PCa at the first re-biopsy was statistically correlated with the PSA value - for which a cut-off value of 7 ng/mL was identified - and with an anomalous rectal prostatic examination at the time of the initial biopsy. Differently, the risk of diagnosing PCa after the first re-biopsy correlated with the number of cores positive for PIN at the initial biopsy - for which a cut-off of 4 was identified - and to the ratio between these and the total number of cores, defined as PIN density - for which a cut-off of 50% was determined. Discussion and Conclusions It is possible to suggest a tailored protocol of controls in patients with a diagnosis of PIN on the basis of the data available at the initial biopsy: a) high PSA value and/or an anomalous prostatic rectal examination: the diagnosis of PCa is probably just unacknowledged by the initial sampling and it is advisable to carry out an early re-biopsy; b) number of cores with PIN equal to or higher than 4 and/or PIN density equal to or higher than 50%: a true transition from PIN to PCa is likely to happen with time and it is advisable to carry out a delayed re-biopsy; c) no risk factors: just clinical and PSA monitoring to establish the indication to re-biopsy.

Immunohistochemical application of D2-40 as basal cell marker in evaluating atypical small acinar proliferation of initial routine prostatic needle biopsy materials

D2-40 has been recently discovered as a lymphatic endothelial cell marker, and some investigators have found that D2-40 is also expressed in myoepithelial cells of salivary gland or breast. In this study, we evaluated D2-40 expression of basal cells and applied D2-40 immunohistochemistry in the combination of P504S, cytokeratin 5, and p63 for ten lesions with atypical small acinar proliferation (ASAP) in initial prostatic needle biopsy. As a result, D2-40 was expressed in basal cells, lymphatic endothelial cells, and some stromal fibroblasts of normal prostatic tissue. Among ten ASAP lesions, the final diagnosis of seven lesions was resolved by combination immunohistochemistry. D2-40 was comparable to cytokeratin 5 and p63 as a basal cell marker, and there were no lesions that failed to provide an accurate final diagnosis using only D2-40 immunohistochemistry without cytokeratin 5 or p63. However, we found some D2-40-positive stromal fibroblasts or D2-40-positive lumen-collapsed lymphatic vessels neighboring atypical glands. Pathologists should pay attention to avoid recognizing these cells as basal cells. In conclusion, the combination of immunohistochemistry of P504S, cytokeratin 5, p63, and D2-40 may contribute to the accurate diagnosis of ASAP in the initial prostatic needle biopsy.

Improved Resolution of Diagnostic Problems in Selected Prostate Needle Biopsy Specimens by Using the ASAP Workup

This study assessed the value of an atypical small acinar proliferation (ASAP) workup consisting of preparing new recut sections from the paraffin block and performing H&E-stained sections and immunostains (using the antibody cocktail for p63, cytokeratins 5 and 14, and alpha-methylacyl coenzyme A racemase) on the slides. We compared the ASAP workup with the interval workup, the common practice of performing the same immunostains on the saved interval sections, in 105 cases because of focal glandular atypia on the original H&E-stained sections. There were no specimens in which only the interval workup showed a changed diagnosis, but there were 23 specimens (21.9%) in which the preliminary diagnosis was changed to a definitive diagnosis of carcinoma (10 specimens) or a specific benign diagnosis (13 specimens) based solely on the findings of the ASAP workup. The ASAP workup is recommended as a very useful histologic tool for resolving diagnostic problems in prostate needle biopsy specimens.

External Validation of Urinary PCA3-Based Nomograms to Individually Predict Prostate Biopsy Outcome

BackgroundPrior to safely adopting risk stratification tools, their performance must be tested in an external patient cohort. ObjectiveTo assess accuracy and generalizability of previously reported, internally validated, prebiopsy prostate cancer antigen 3 (PCA3) gene-based nomograms when applied to a large, external, European cohort of men at risk of prostate cancer (PCa). Design, setting, and participantsBiopsy data, including urinary PCA3 score, were available for 621 men at risk of PCa who were participating in a European multi-institutional study. InterventionAll patients underwent a ≥10-core prostate biopsy. Biopsy indication was based on suspicious digital rectal examination, persistently elevated prostate-specific antigen level (2.5–10 ng/ml) and/or suspicious histology (atypical small acinar proliferation of the prostate, >/= two cores affected by high-grade prostatic intraepithelial neoplasia in first set of biopsies). MeasurementsPCA3 scores were assessed using the Progensa assay (Gen-Probe Inc, San Diego, CA, USA). According to the previously reported nomograms, different PCA3 score codings were used. The probability of a positive biopsy was calculated using previously published logistic regression coefficients. Predicted outcomes were compared to the actual biopsy results. Accuracy was calculated using the area under the curve as a measure of discrimination; calibration was explored graphically. Results and limitationsBiopsy-confirmed PCa was detected in 255 (41.1%) men. Median PCA3 score of biopsy-negative versus biopsy-positive men was 20 versus 48 in the total cohort, 17 versus 47 at initial biopsy, and 37 versus 53 at repeat biopsy (all p≤0.002). External validation of all four previously reported PCA3-based nomograms demonstrated equally high accuracy (0.73–0.75) and excellent calibration. The main limitations of the study reside in its early detection setting, referral scenario, and participation of only tertiary-care centers. ConclusionsIn accordance with the original publication, previously developed PCA3-based nomograms achieved high accuracy and sufficient calibration. These novel nomograms represent robust tools and are thus generalizable to European men at risk of harboring PCa. Consequently, in presence of a PCA3 score, these nomograms may be safely used to assist clinicians when prostate biopsy is contemplated.

The predictive value of HGPIN and ASAP for the subsequent diagnosis of prostate cancer in the Reduction by Dutasteride of Cancer Events (REDUCE) study.

4561 Background: REDUCE was a 4-year, randomized placebo (pbo) controlled study of prostate cancer (PCa) risk reduction with once daily dutasteride 0.5 mg (dut). This analysis examines the effect of dut on initial detection of high-grade prostatic intraepithelial neoplasia (HGPIN) and/or atypical small acinar proliferation (ASAP) and the incidence of PCa on subsequent biopsy. Methods: Eligible men were aged 50–75 years, had a serum PSA 2.5–10.0 ng/ml, and a single, negative (no PCa, HGPIN or ASAP) biopsy of 6–12 cores in the 6 months prior to enrollment (4126 subjects randomized to pbo, 4105 dut). Ten-core prostate biopsies were taken at 2 and 4 years and examined for evidence of PCa. For subjects with 2-year biopsies and no PCa (2866 pbo, 2867 dut), the initial incidence of ASAP, HGPIN (without ASAP), and ASAP or HGPIN was compared between treatment groups using Fisher's exact test. PCa incidence in a subsequent biopsy was also compared between treatment groups with Fisher's exact test. Results: PCa incidence in subjects biopsied was 17.2% (pbo) and 13.4% (dut) in Years 1–2; and 11.8% (pbo) and 9.1% (dut) in Years 3–4. Dut was associated with a lower incidence of ASAP and/or HGPIN (p≤0.007; Table). For subjects with ASAP and/or HGPIN in initial study biopsy who had a subsequent biopsy (median time between biopsies 2 years), the incidence of PCa was higher vs. overall PCa incidence during Years 3–4. If a man was diagnosed with HGPIN or ASAP while taking dut, the likelihood of a future PCa diagnosis was similar to that of the pbo group. Conclusions: HGPIN and ASAP conferred a 2- and 3-fold increased risk of subsequent PCa, respectively compared to the overall rates for PCa in Years 3–4. Dut significantly reduced the incidence of HGPIN and/or ASAP with no significant differences vs. pbo observed in the risk of subsequent PCa. Incidence Pbo Dut p value ASAP 1st dx ASAP 206/2,866 (7.2%) 156/2,867 (5.4%) 0.007 Subsequent PCa 39/116 (33.6%) 29/95 (30.5%) 0.66 HGPIN and no ASAP 1st dx HGPIN 243/2,866 (8.5%) 143/2,867 (5.0%) <0.0001 Subsequent PCa 23/109 (21.1%) 12/63 (19.0%) 0.85 ASAP and/or HGPIN 1st dx ASAP/HGPIN 434/2,866 (15.1%) 288/2,867 (10.0%) <0.0001 Subsequent PCa 61/221 (27.6%) 40/153 (26.1%) 0.81 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Bostwick Laboratories, Ferring Pharmaceutical, GlaxoSmithKline Astellas Pharma, GlaxoSmithKline, Orion Pharma Bostwick Laboratories, GlaxoSmithKline Astellas Pharma, Ferring Pharmaceutical, GlaxoSmithKline, Orion Pharma GlaxoSmithKline GlaxoSmithKline

Predicting prostate biopsy outcome: artificial neural networks and polychotomous regression are equivalent models

Complex statistical models utilizing multiple inputs to derive a risk assessment may benefit prostate cancer (PC) detection where focus has been on prostate-specific antigen (PSA). This study develops a polychotomous logistic regression (PR) model and an artificial neural network (ANN) for predicting biopsy results, particularly for clinically significant PC. There were 3,025 men undergoing TRUS-guided biopsy (BX) with PSA <10ng/ml selected. BX outcome classified as benign, atypical small acinar proliferation or high-grade prostatic intraepithelial neoplasia (ASAP/PIN), non-significant (NSPC) or clinically significant PC (CSPC). PR and ANN models were developed to distinguish between BX categories. Predictors were age, PSA, abnormal digital rectal examination (DRE), positive transrectal ultrasound (TRUS) and prostate volume. Among the BXs, 44% were benign, 14% ASAP/PIN, 16% NSPC and 25% CSPC. Median age, PSA and volume were 64years, 5.7ng/ml and 50cc. TRUS lesion was present in 47%, and DRE was abnormal in 39%. PR and ANN models did not differ on percentage BX outcomes correctly predicted (55, 57%, respectively) and were equally poor for both ASAP/PIN (0%) and NSPC (2%). For PR and ANN, 74-78% ASAP/PIN predicted benign, 2% NSPC and 20-24% CSPC. For NSPC, 69-71% predicted benign, 27-29% CSPC. Benign outcomes were well identified (86-88%), although 12-13% classified CSPC. CSPC was correctly identified in 65-66% with misclassifications largely benign (33% for PR and ANN). Neither PR nor ANN was able to distinguish between the four biopsy outcomes: ASAP/PIN and NSPC were not distinguished from benign or CSPC. ANN did not perform better than PR. Inclusion of additional predictors may increase the performance of statistical models in predicting BX outcome.

Development and validation of a nomogram for predicting a positive repeat prostate biopsy in patients with a previous negative biopsy session in the era of extended prostate sampling

To create a nomogram for predicting the probability of a positive biopsy in men with one or more previous negative biopsies, as the false-negative rate of prostate biopsy in contemporary series remains substantial, and there is a need to identify those with a negative result but with a high risk of having unrecognized prostate cancer. The study included 408 patients from Cleveland Clinic who had one or more repeat biopsies after an initial negative biopsy from 1999 to 2008. Another 470 men with the same criteria were used to validate the nomogram. Nomogram variables included age, family history of prostate cancer, body mass index, findings on a digital rectal examination, prostate-specific antigen (PSA) level, PSA slope, total prostate volume, months from initial negative biopsy session, months from previous negative biopsy, cumulative number of negative cores previously taken and history of high-grade intraepithelial neoplasia or atypical small acinar proliferation. We calculated the nomogram predicted probability in each patient. These predicted outcomes were compared with the actual biopsy results. The area under the receiver operating characteristic (ROC) curve was calculated as a measure of discrimination. The mean number of previous negative biopsies was 1.5, and the mean number of cores per session was 19.1. Of the original development data, 129 men (31.6%) had prostate cancer. A nomogram was constructed that had a concordance index of 0.72, which was greater than any single risk factor. In the validation group the area under the ROC curve was 0.62. Our nomogram for predicting a positive repeat biopsy can provide important additional information to aid the urologist and patient with a negative biopsy in evaluating clinical options.

The presence of prostate cancer on saturation biopsy can be accurately predicted

To improve the ability of our previously reported saturation biopsy nomogram quantifying the risk of prostate cancer, as the use of office-based saturation biopsy has increased. Saturation biopsies of 540 men with one or more previously negative 6-12 core biopsies were used to develop a multivariable logistic regression model-based nomogram, predicting the probability of prostate cancer. Candidate predictors were used in their original or stratified format, and consisted of age, total prostate-specific antigen (PSA) level, percentage free PSA (%fPSA), gland volume, findings on a digital rectal examination, cumulative number of previous biopsy sessions, presence of high-grade prostatic intraepithelial neoplasia on any previous biopsy, and presence of atypical small acinar proliferation (ASAP) on any previous biopsy. Two hundred bootstraps re-samples were used to adjust for overfit bias. Prostate cancer was diagnosed in 39.4% of saturation biopsies. Age, total PSA, %fPSA, gland volume, number of previous biopsies, and presence of ASAP at any previous biopsy were independent predictors for prostate cancer (all P < 0.05). The nomogram was 77.2% accurate and had a virtually perfect correlation between predicted and observed rates of prostate cancer. We improved the accuracy of the saturation biopsy nomogram from 72% to 77%; it relies on three previously included variables, i.e. age, %fPSA and prostate volume, and on three previously excluded variables, i.e. PSA, the number of previous biopsy sessions, and evidence of ASAP on previous biopsy. Our study represents the largest series of saturation biopsies to date.

Variability in Diagnostic Opinion Among Pathologists for Single Small Atypical Foci in Prostate Biopsies

Pathologists are increasingly exposed to prostate biopsies with small atypical foci, requiring differentiation between adenocarcinoma, atypical small acinar proliferation suspicious for malignancy, and a benign diagnosis. We studied the level of agreement for such atypical foci among experts in urologic pathology and all-round reference pathologists of the European Randomized Screening study of Prostate Cancer (ERSPC). For this purpose, we retrieved 20 prostate biopsies with small (most <1 mm) atypical foci. Hematoxylin and eosin-stained slides, including 10 immunostained slides were digitalized for virtual microscopy. The lesional area was not marked. Five experts and 7 ERSPC pathologists examined the cases. Multirater kappa statistics was applied to determine agreement and significant differences between experts and ERSPC pathologists. The kappa value of experts (0.39; confidence interval, 0.29-0.49) was significantly higher than that of ERSPC pathologists (0.21; confidence interval, 0.14-0.27). Full (100%) agreement was reached by the 5 experts for 7 of 20 biopsies. Experts and ERSPC pathologists rendered diagnoses ranging from benign to adenocarcinoma on the same biopsy in 5 and 9 biopsies, respectively. Most of these lesions comprised between 2 and 5 atypical glands. The experts diagnosed adenocarcinoma (49%) more often than the ERSPC pathologists (32%) (P<0.001). As agreement was particularly poor for foci comprising <6 glands, we would encourage pathologists to obtain intercollegial consultation of a specialized pathologist for these lesions before a carcinoma diagnosis, whereas clinicians may consider to perform staging biopsies before engaging on deferred or definite therapy.

Accurate prediction of repeat prostate biopsy outcomes by a mitochondrial DNA deletion assay

Several cancers are characterized by large-scale mtDNA deletions. We previously provided evidence that one of these deletions has potential utility in resolving false from true-negative prostate needle biopsies. This study was to assess the clinical value of this deletion in predicting re-biopsy outcomes. We used a quantitative polymerase chain reaction assay to measure the levels of the deletion in individual negative needle biopsies from 101 patients who had a repeat biopsy within a year with known outcomes. Using an empirically established cycle threshold (Ct) cutoff of 31, and the lowest Ct for each patient as diagnostic of prostate cancer, as well as the histopathologic diagnosis on second biopsy, we calculated the clinical performance of the deletion. The Ct cutoff at 31 gave a sensitivity and specificity of 84 and 54%, respectively, with the area under a receiver-operating characteristics curve of 0.749. The negative predictive value was 91%. The assay was able to predict the presence of a missed tumor in 17 out of 20 men a year before diagnosis. This ancillary test appears to identify men who do not require a repeat biopsy with a high degree of certainty. The results suggest that the majority of men with atypical small acinar proliferation have a concurrent missed tumor and therefore require close monitoring for early detection.

A nomogram for predicting upgrading in patients with low‐ and intermediate‐grade prostate cancer in the era of extended prostate sampling

Diagnostic (exploratory cohort). 2b. To develop a nomogram to predict the probability that the pathological Gleason sum (GS) will be higher than that indicated by the biopsy, suggesting a higher risk for the patient presumed to be at low risk, as a substantial proportion of patients with low and intermediate grade on biopsy are upgraded on interpretation of the radical prostatectomy (RP) specimens, but a similar clarification of accurate Gleason scoring is not available in patients with no surgical histology. The study included 1017 patients who had RP after biopsy showing GS 6 and 7 (3 + 4) from 2000 to 2007. Nomogram predictor variables included age, race, digital rectal examination, prostate-specific antigen (PSA) level, number of cores taken, number of positive cores, maximum percentage cancer in any core, number of previous biopsies, prostate volume, clinical stage, high-grade prostatic intraepithelial neoplasia, atypical small acinar proliferation, inflammation and perineural invasion. We calculated the nomogram-predicted probability in each patient. The area under the receiver operating characteristic curve was calculated as a measure of discrimination, and the calibration was assessed graphically. The mean age of the patients was 60 years, the mean PSA level 6.62 ng/mL; 336 patients were upgraded (33%), 623 remained the same (61.3%) and 58 were downgraded (5.7%). A nomogram for predicting the possibility of upgrading was constructed that had a concordance index of 0.68. The nomogram was well calibrated. Our nomogram for predicting upgrading provides important additional information for deciding on treatment to both the urologist and the patient with low- and intermediate-grade prostate cancer. It might prove useful when the possibility of a more aggressive Gleason variant can change the management, and is especially meaningful when management options other than surgery are selected based on the inability to recognize the true pathological actual GS.

Pathologic Results of Radical Prostatectomies in Patients with Simultaneous Atypical Small Acinar Proliferation and Prostate Cancer

PurposeThe incidence of adenocarcinoma on a subsequent biopsy following a diagnosis of atypical small acinar proliferation (ASAP) ranges from 34% to 60%. We reexamined radical prostatectomy (RP) specimens of patients diagnosed as having synchronous ASAP with prostate cancer (PCa) to evaluate pathological entities and the clinical significance of ASAP.Materials and MethodsFrom January 2007 to December 2008, a total of 118 patients who had been diagnosed with adenocarcinoma on prostate needle biopsy underwent RP. Forty-six of the 118 patients (39%) were diagnosed as having synchronous ASAP with PCa on the prostate needle biopsy. Using whole-mount sections and prostate mapping, we evaluated the RP specimens that were close sections to the ASAP on prostate needle biopsy. All tissues were examined by immunohistochemistry with high molecular weight cytokeratin (34βE12), p63, and AMACR/P504S added to initial H&E stains by one pathologist.ResultsThirty-six of the 46 patients (78%) were diagnosed as having adenocarcinoma at sites of ASAP on the initial prostate needle biopsies. The Gleason score was 5 to 6 in 22 patients (61%), 7 in 3 (8%), and unknown due to multifocal and microfocal lesions in 11 (31%). The tumor volume of 14 of the 36 patients (39%) was 0.5 cc or less and was unknown due to multifocal and microfocal lesions in 8 (22%).ConclusionsMost ASAP on initial prostate needle biopsy was a true pathological entity, in other words, prostatic adenocarcinoma. Aggressive approaches including more extended repeat biopsy with additional biopsy of the site of the ASAP are needed to diagnose PCa in patients with ASAP.

Predictive Factors of Prostate Cancer at Repeat Biopsy in Patients with an Initial Diagnosis of Atypical Small Acinar Proliferation of the Prostate

PurposeThe factors that predict prostate cancer detection on repeat biopsy were evaluated in patients with atypical small acinar proliferation (ASAP) on the initial biopsy.Materials and MethodsFrom 2003 to 2008, 3,130 men with suspected prostate cancer underwent a prostate needle biopsy, and 244 (7.8%) were diagnosed as having ASAP. One hundred seventy of 244 patients were rebiopsied at least once more. They were classified into a prostate cancer group and a noncancer group according to the final pathological diagnosis. The database of rebiopsied patients included age, initial prostate-specific antigen (PSA), PSA density (PSAD), PSA velocity (PSAV), total prostate volume (TPV), and transitional zone volume of the prostate (TZV). We compared differences in the aforementioned parameters between the 2 groups.ResultsA total of 57 patients (33.5%) with ASAP were ultimately shown to have prostate cancer. Univariate analysis showed that PSAD (p=0.002), PSAV (p=0.001), TPV (p=0.035), and TZV (p=0.005) differed significantly between the cancer and noncancer groups. The results of the multivariate analysis showed that PSAD (p=0.022), PSAV (p<0.001), and TPV (p=0.037) had a statistically significant correlation with cancer detection.ConclusionsPSAD, PSAV, and TPV are predictive factors of prostate cancer in patients with an initial diagnosis of ASAP of the prostate. Although repeat biopsy is mandatory irrespective of PSA values, the follow-up of PSA may help to estimate the probability of cancer in these men.

False-negative Prostate Needle Biopsies: Frequency, Histopathologic Features, and Follow-up

Little is known about the frequency, histopathologic characteristics, and clinical consequences of false-negative prostate biopsies, that is, biopsies classified as benign but containing adenocarcinoma or atypical suspicious glands [atypical small acinar proliferations (ASAP)]. Objective of this study was to evaluate false-negative prostate biopsy in a prostate cancer screening setting. Prostate biopsy sets of 196 participants of a screening trial, which had been reported as "benign" at initial diagnosis, followed by a diagnosis of adenocarcinoma in a subsequent screening round were reviewed by 2 urologic pathologists. Adenocarcinoma was identified in 19 biopsy cores corresponding to 16 (8.2%) patients and ASAP in 24 cores, corresponding to 19 patients (9.7%). All missed prostate cancers were Gleason score 6 (3+3). After correction for patient selection, the overall false-negative biopsy rate was estimated to be 2.4%; 1.1% for prostate cancer; and 1.3% for ASAP. Clinicopathologic features at the time of initial biopsy and of subsequent prostate cancer diagnosis did not differ between patients with a false-negative or true benign biopsy. Relatively low number of atypical glands (<10 glands), intense intermingling with preexistent glands or lack of architectural disorganization were the most prominent risk factors for a false-negative diagnosis. Another potential pitfall was the presence of prostate cancer variants, as 1 adenocarcinoma was of foamy gland type and 3 of pseudohyperplastic type. Routine examination of at least 1 level of prostate biopsy sets at high magnification and awareness of histologic prostate cancer variants might reduce the risk of missing or misinterpreting a relevant lesion at prostate biopsy evaluation.

Outcome of Prostate Biopsy in Men Younger than 40 Years of Age with High Prostate-Specific Antigen (PSA) Levels

PurposeProstate cancer is rarely diagnosed in men younger than 40 years of age. At present, the available data show a low rate of cancer detection from prostate-specific antigen (PSA) screening of this group of young men. We analyzed the outcome of prostate biopsy results in patients of this age group with a high PSA.Materials and MethodsBetween October 1997 and August 2008, a total of 81 men less than 40 years of age were referred from the Health Care Promotion Center as the result of elevated PSA levels. Six men with prostatitis were excluded. The remaining 75 men were asymptomatic and had normal findings on the digital rectal examination (DRE) and were selected to have a transrectal ultrasound-guided prostate biopsy for suspected prostate cancer. The patients with sustained high PSA levels underwent repeat biopsies.ResultsThe median age of the 75 men was 33 years (range, 26-40 years) and the mean PSA level was 6.57 ng/ml (range, 4.32-13.45 ng/ml). The results of the primary biopsy was 1 (1.3%) case of prostate cancer, 70 cases (93%) with benign tissue, 2 cases (2.6%) with inflammation, and 1 case each (1.3%) with high grade intraepithelial neoplasia (HGPIN) and atypical small acinar proliferation (ASAP). Of the 10 men who underwent a second biopsy, all had benign findings. Three of the men who underwent a third biopsy all had benign tissue findings.ConclusionsThe prostate cancer detection rate in young men less than 40 years of age with high PSA levels and normal DREs was very low. Repeat biopsy for sustained high PSA levels in young men less than 40 years of age may not be indicated.

Detection rate and factors predictive the presence of prostate cancer in patients undergoing ultrasonography-guided transperineal saturation biopsies of the prostate

To assess the prostate cancer detection rate and predictive factors for prostate cancer after transrectal ultrasonography (TRUS)-guided transperineal saturation re-biopsies of the prostate, using a 24-core scheme. We evaluated 143 consecutive patients undergoing TRUS-guided transperineal saturation re-biopsy of the prostate using a 24-core scheme. The inclusion criteria were a previous negative biopsy and a prostate-specific antigen (PSA) level of > or =10.0 ng/mL, or of 4.0-10.0 ng/mL with a free/total ratio of <20% or an abnormal digital rectal examination or previous high-grade prostatic intraepithelial neoplasia (HGPIN) or atypical small acinar proliferation (ASAP). The mean (sd) age of the patients was 66.5 (6.1) years and the median (interquartile range) PSA level was 9.0 (6.1-12.8) ng/mL. The number of previous biopsies was one in 59% of patients, two in 26% and three or more in 15%. We detected prostate cancer in 26%, ASAP in 5.6% and HGPIN in 2.1%. The cancer detection rate was 47%, 25.5% and 14% for prostate volumes of <40, 40-60 and > or =60 mL, respectively (P = 0.002). On a multivariate analysis the total prostate volume (40-60 vs <40 mL, hazard ratio 5.683; >60 vs <40 mL, hazard ratio 6.965; P = 0.01) was the only significant predictor of prostate cancer at saturation biopsy. TRUS-guided transperineal saturation re-biopsy of the prostate using a 24-core scheme resulted in a high cancer detection rate also in patients who had had two or more previous biopsies. The total prostate volume was the only predictor of prostate cancer.

Considerations on prostate cancer: diagnosis and treatment decisions

Discussion on the accuracy of PSA and biopsy for the selection of tailored treatment has been generated from several Welds. The inherent variability of total, free and complex PSA has been demonstrated. Analytical sample handling, laboratory processing, assay performance, and standardisation as well as biological variation are factors inXuencing its impact. Bogermann and colleagues from the University of Essen, Germany draw attention to the fact that diVerent pre-analytic timetables of blood samples in inpatient and out-patient setups lead to subsequent diVerent fPSA degradation, thereby shedding light on the need for diVerent cut-oV values for biopsy indication in these clinical settings. Prostate biopsy has evolved from a paradigm of a small number of random biopsies to a systematic, numerically standardised, and anatomically controlled strategy. Over the past several years, data have demonstrated the need for deWned biopsy strategies for detecting, accurately grading, and staging prostate cancer in varying patient populations. Saturation biopsy schemes have proven beneWcial in repeat biopsy and active surveillance protocols. Ploussard and colleagues from Creteil, Paris, France, report on how to follow-up prostate cancer detection with repeated biopsies after high-grade prostatic intraepithelial neoplasia (HGPIN) and atypical small acinar proliferation (ASAP) following their initial 21-core extended biopsy scheme. Proving the sensitivity and speciWcity of artiWcial neuronl networks (ANN) for prostate cancer in a diVerent “statistical environment” is a necessary part of the evaluation of any ANN. Meijer and colleagues from Hertogenbosch, The Netherlands, report on their results on prostate biopsy predicting model of the ANN Prostataclass of the Universitatsklinikum Charite, Berlin, Germany, from their database. Trifecta (continence, potency and oncological result) has been the issue of discussions in recent years but lacking single center data for intra-institutional comparisons. Drouin and colleagues from Pitie-Salpetriere, University of Paris, France, compared the oncological midterm outcome over 50 months of patients treated during the same period in a single institution. Gilberti and colleagues from Savona, Italy present a prospective randomised trial including the mid-term follow-up data comparing brachytherapy with radical prostatectomy with regard to Trifecta. As with any other surgical treatment option, laparoscopy carries the risk of major surgical complications. Teber and colleagues from Heilbronn, Germany, present their experience with identifying and treating ureteral injury during laparoscopic radical prostatectomy in their institutions series of more than 2,100 patients. Rinnab and colleagues from the University of Ulm, Germany have been involved in detection methods for patients with biochemical recurrence after treatment of prostate cancer, which remains a diagnostic and therapeutic challenge. Here, they display their results on [(11)C] choline PET/CT in patients with biochemical recurrence after radical prostatectomy. Androgen-deprivation therapy is associated with important adverse eVects which have an impact on quality of life, especially in men over 70 years of age. A further disadvantages of continuous application is the cost consideration. Numerous phase II trials have shown the eYcacy of intermittent androgen withdrawal with a reduction in inter-treatment intervals. Prapotnich and colleagues from Montsouris, Paris, France, report their oncological results over a period T. R. W. Herrmann (&) · A. S. Merseburger · M. Burchardt Department of Urology and Urologic Oncology, Hannover Medical School, Carl-Neuberg-Strase 1, 30625 Hannover, Germany e-mail: Herrmann.Thomas@mh-hannover.de