Secondary Gleason Grade Research Articles

Learning to predict prostate cancer recurrence from tissue images

Roughly 30% of men with prostate cancer who undergo radical prostatectomy will suffer biochemical cancer recurrence (BCR). Accurately predicting which patients will experience BCR could identify who would benefit from increased surveillance or adjuvant therapy. Unfortunately, no current method can effectively predict this. We develop and evaluate PathCLR, a novel semi-supervised method that learns a model that can use hematoxylin and eosin (H&E)-stained tissue microarrays (TMAs) to predict prostate cancer recurrence within 5 years after diagnosis. The learning process involves 2 sequential steps: PathCLR (a) first employs self-supervised learning to generate effective feature representations of the input images, then (b) feeds these learned features into a fully supervised neural network classifier to learn a model for predicting BCR. We conducted training and evaluation using 2 large prostate cancer datasets: (1) the Cooperative Prostate Cancer Tissue Resource (CPCTR) with 374 patients, including 189 who experienced BCR, and (2) the Johns Hopkins University (JHU) prostate cancer dataset of 646 patients, with 451 patients having BCR. PathCLR’s (10-fold cross-validation) F1 score was 0.61 for CPCTR and 0.85 for JHU. This was statistically superior (paired t-test with P <.05) to the best-learned model that relied solely on clinicopathological features, including PSA level, primary and secondary Gleason Grade, etc. We attribute the improvement of PathCLR over models using only clinicopathological features to its utilization of both learned latent representations of tissue core images and clinicopathological features. This finding suggests that there is essential predictive information in tissue images at the time of surgery that goes beyond the knowledge obtained from reported clinicopathological features, helping predict the patient’s 5-year outcome.

Five-year Outcomes of Magnetic Resonance Imaging–based Active Surveillance for Prostate Cancer: A Large Cohort Study

BackgroundAlthough the use of multiparametric magnetic resonance imaging (mpMRI) in active surveillance (AS) for prostate cancer is of increasing interest, existing data are derived from small cohorts. ObjectiveWe describe clinical, histological, and radiological outcomes from an established AS programme, where protocol-based biopsies were omitted in favour of MRI-led monitoring. Design, setting, and participantsData on 672 men enrolled in AS between August 2004 and November 2017 (inclusion criteria: Gleason 3 + 3 or 3 + 4 localised prostate cancer, presenting prostate-specific antigen <20 ng/ml, and baseline mpMRI) were collected from the University College London Hospital (UCLH) database. Outcome measurements and statistical analysisPrimary outcomes were event-free survival (EFS; event defined as prostate cancer treatment, transition to watchful waiting, or death) and treatment-free survival (TFS). Secondary outcomes included rates of all-cause or prostate cancer–related mortality, metastasis, and upgrading to Gleason ≥4 + 3. Data on radiological and histological progression were also collected. Results and limitationsMore than 3800 person-years (py) of follow-up were accrued (median: 58 mo; interquartile range 37–82 mo). Approximately 84.7% (95% confidence interval [CI]: 82.0–87.6) and 71.8% (95% CI: 68.2–75.6) of patients remained on AS at 3 and 5 yr, respectively. EFS and TFS were lower in those with MRI-visible (Likert 4–5) disease or secondary Gleason pattern 4 at baseline (log-rank test; p < 0.001). In total, 216 men were treated. There were 24 deaths, none of which was prostate cancer related (6.3/1000 py; 95% CI: 4.1–9.5). Metastases developed in eight men (2.1 events/1000 py; 95% CI: 1.0–4.3), whereas 27 men upgraded to Gleason ≥4 + 3 on follow-up biopsy (7.7 events/1000 py; 95% CI: 5.2–11.3). ConclusionsThe rates of discontinuation, mortality, and metastasis in MRI-led surveillance are comparable with those of standard AS. MRI-visible disease and/or secondary Gleason grade 4 at baseline are associated with a greater likelihood of moving to active treatment at 5 yr. Further research will concentrate on optimising imaging intervals according to baseline risk. Patient summaryIn this report, we looked at the outcomes of magnetic resonance imaging (MRI)-based surveillance for prostate cancer in a UK cohort. We found that this strategy could allow routine biopsies to be avoided. Secondary Gleason pattern 4 and MRI visibility are associated with increased rates of treatment. We conclude that MRI-based surveillance should be considered for the monitoring of small prostate tumours.

Automated Text Mining of Prostate Pathology Reports Extracted from an Electronic Medical System, using a Rule-Based Approach

Retrospective analysis of large-scale, prostate cancer databases to identify trends in cancer care and outcomes require detailed histopathologic characterization. Manual extraction of these characteristics from prostate pathology reports is a time-consuming process that is prone to human error. Our goal was to develop a rule-based software algorithm that was capable of automatically extracting pertinent characteristics (primary and secondary Gleason grade, maximum core involvement, number of positive and total cores) from prostate pathology reports. Prostate pathology reports were manually extracted from our institution’s electronic medical record system for 135 patients. The dataset was split into a training and testing set consisting of 110 and 25 patients, respectively. The training set was examined by hand to identify patterns and linguistic features that could be used to build the rules for extracting the clinical characteristics. During the training phase, it was noted that a different set of rules was required for outside slide reviews as these often presented the results in summary format as opposed to the core-by-core breakdown of those authored at our institution. These rules were then implemented in the statistical software platform, R. The performance of the algorithm was assessed in both training and testing sets by comparing the software predictions of the clinical characteristics to those made by a human observer. Of the 135 pathology reports, 29 were outside slide reviews (23 in training, and 6 in testing). The algorithm was able to correctly identify the primary and secondary Gleason grade, as well as the maximum core involvement percentage in 100% (135/135) of the data set. Due to ambiguity in reporting, four of the reports were excluded for the total core analysis, while two were excluded for the positive core analysis. The algorithm correctly identified the total cores in 95% (124/131) of the data set and the positive cores in 98% (131/133) of the data set. The testing set accuracy for the total and positive cores was 83% (19/23) and 96% (23/24), respectively. Analysis of errors revealed that four of the seven incorrectly identified total cores and both incorrectly identified positive cores were in outside slide reviews. The rule-based software algorithm was able to correctly extract and identify the primary and secondary Gleason grades, maximum core involvement, and number of positive and total cores in the majority of the examined prostate pathology reports. Standardized reporting, including a core-by-core breakdown, may lead to improved accuracy of text-mining algorithms and mitigate the need for human registrars.

Is Prostate Imaging Reporting and Data System Version 2 Sufficiently Discovering Clinically Significant Prostate Cancer? Per-Lesion Radiology-Pathology Correlation Study.

The objective of our study was to evaluate the performance of multiparametric MRI with Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) for detecting prostate cancer (PCA) and clinically significant PCA through this per-lesion one-to-one correlation study between pathologically proven lesions and MRI-visible lesions. A total of 93 PCA lesions from 44 patients who underwent radical prostatectomy were included in this retrospective study. Two radiologists scored every visible lesion with a PI-RADSv2 score of 3, 4, or 5 in each patient's multiparametric MRI examination using PI-RADSv2. A per-lesion one-to-one correlation between MRI-visible lesions and pathologically confirmed PCA lesions was conducted during regular radiology-pathology meetings at our center. The detection rates of clinically significant PCA and the proportions of clinically significant PCAs from MRI-visible and MRI-invisible PCAs were calculated. The performance of PI-RADSv2 for detecting clinically significant PCA was evaluated using the positive predictive value (PPV), negative predictive value (NPV), and area under the ROC curve (AUC) value. Using a PI-RADSv2 score of 3, 4, or 5 as an MRI-visible lesion, 46.88% of clinically significant PCA lesions were detected. The PPV, NPV, and AUC were 96.77%, 45.16%, and 0.72, respectively. Tumor volume and secondary Gleason grade showed a statistically significant difference between MRI-visible and MRI-invisible clinically significant PCAs. Multiparametric MRI with PI-RADSv2 missed a considerable number of clinically significant PCA lesions in this per-lesion analysis, causing a relatively low NPV and diagnostic performance compared with previous per-patient studies. However, the high PPV indicates that multiparametric MRI with PI-RADSv2 may be useful for follow-up of active surveillance and planning focal therapy.

Metabolic syndrome is not associated with greater evidences of proliferative inflammatory atrophy and inflammation in patients with suspected prostate cancer

Introduction and objectivesTo evaluate the association between metabolic syndrome (MetS) and proliferative inflammatory atrophy (PIA) in patients with suspected prostate cancer (PCa). Patients and methodsFrom June 2015 to July 2016, we conducted the FIERY (Flogosis Increased Events of pRostatic biopsY) study at the Urology section, Department of Surgery of the University of Catania (Local registration number: #131/2015).A total of 205 patients with elevated prostate-specific antigen (≥ 4 ng/ml) or clinical suspicion of PCa who underwent primary transperineal prostate biopsy were included in this cross-sectional study.The assessment of PIA, HGPIN, and PCa were performed by 2 experienced pathologists and samples were investigated for the presence of an inflammatory infiltrate, according to the Irani score. Primary and secondary Gleason grade of tumor in positive biopsies were evaluated according to the 2016 ISUP Modified Gleason System. ResultsIn the entire cohort, median age was 68.0 (interquartile range: 62.0–74.5), median prostate-specific antigen was 6.5 (interquartile range: 5.51–9.57). The prevalence of MetS was 34.1%, the detection rate of PCa was 32.7%, the rate of PIA was 28.3%, the rate of HGPIN was 32.2%, whereas the rate of severe intraprostatic inflammation (Irani-score ≥4) was 28.8%.When comparing clinical and histological variables in patients without and with PIA, metabolic aberrations where not significantly different in both groups. We did not find statistical association in detection rate of PCa (29.3% vs. 34.0%; P = 0.07) and HGPIN (27.6% vs. 34.0%; P = 0.37) in patients with and without PIA, respectively. When considering metabolic aberrations, MetS was not associated with Irani-score ≥4 (28.6% vs. 28.4%; P = 0.96) and none of each component was statistically predictive of severe inflammation.At the multivariable logistic regression analysis, PIA, HGPIN, and MetS were not associated with greater risk of PCa. ConclusionIn this study, we did not show an association between MetS and PIA and PCa. Although the small sample size and the cross-sectional nature of the study, we do not suppose that MetS could be associated with greater evidence of PIA. Further studies should be conducted to evaluate the exact nature of this pathological lesion.

Tumor marker α-fetoprotein receptor does not discriminate between benign prostatic disease and prostate cancer.

The α-fetoprotein receptor (RECAF) is a proposed novel tumor marker for detecting several different types of tumors, including prostate cancer (PCa). The aim of the study was to evaluate RECAF in discriminating benign prostatic conditions from PCa and to compare it with prostate-specific antigen (PSA). A total of 64 patients with elevated serum PSA levels and/or abnormal digital rectal examination of the prostate referred to a tertiary center for transrectal ultrasound (TRUS) biopsy of the prostate were prospectively enrolled in the study from January 2009 to April 2010. Serum RECAF, total PSA (tPSA) and free PSA (fPSA) concentrations were measured. The results were correlated with histopathologic findings using the Mann-Whitney U test and Kruskal-Wallis χ2 test. The median RECAF concentration was 5.34 U/L in the benign pathology group of patients and 4.72 U/L in the malignant pathology group. The difference was not statistically significant. RECAF density, tPSA and fPSA concentrations and tPSA density were significantly different between the benign and malignant pathology groups (p = 0.033, p = 0.000, p = 0.002 and p = 0.000, respectively). RECAF concentration and RECAF density did not differ significantly in the subgroups of PCa patients stratified according to Gleason score, predominant primary Gleason grade or maximum primary Gleason grade, but in predominant secondary Gleason grade and maximum secondary Gleason grade, significant differences were found (p = 0.007 and p = 0.004, respectively). The results of the study did not confirm the RECAF tumor marker as an alternative way to discriminate between groups of patients with benign prostatic conditions and PCa, and its concentration and density do not differ among PCa histopathologic groups.

Most Gleason 8 Biopsies are Downgraded at Prostatectomy—Does 4 + 4 = 7?

Nonrepresentative biopsy sampling of prostate cancers with a biopsy Gleason score of 8 can adversely influence decisions regarding androgen deprivation in men receiving primary radiation therapy. The frequency of and factors associated with downgrading Gleason 8 biopsies at prostatectomy are not well known. We used records from NCDB (National Cancer Database), a hospital based registry in the United States, of 72,556 men with prostate cancer diagnosed from 2010 to 2013, including 5,474 with Gleason 8 biopsies and no other high progression risk criteria according to NCCN (National Comprehensive Cancer Network®) Guidelines®. The prevalence of Gleason 8 downgrading was calculated. Generalized estimating equation multivariable regression models were used to estimate the prevalence ratios and 95% CIs of downgrading by demographic and clinical factors, and evaluate the association of Gleason 8 downgrading with cT (clinical T) to pathological T category up staging. Of 5,474 Gleason 8 biopsies in men lacking other high progression risk criteria 3,263 (60%) were downgraded, changing the progression risk category from high to intermediate. A higher prevalence of Gleason 8 downgrading was significantly and independently associated with decreasing age, African American race, lower cT category, lower prostate specific antigen quartile and certain combinations of primary and secondary Gleason grades (3 + 5 greater than 4 + 4 greater than 5 + 3). Gleason 8 downgrading in cases of cT less than 3 was independently and significantly associated with a lower prevalence of up staging (prevalence ratio = 0.65, 95% CI 0.61-0.69). Downgrading Gleason 8 biopsies is common. Patient evaluation based on Gleason 8 biopsies often results in overestimating progression risk and disease extent, which may lead to overtreatment.

Updated Nomogram Incorporating Percentage of Positive Cores to Predict Probability of Lymph Node Invasion in Prostate Cancer Patients Undergoing Sentinel Lymph Node Dissection.

Objectives: To update the first sentinel nomogram predicting the presence of lymph node invasion (LNI) in prostate cancer patients undergoing sentinel lymph node dissection (sPLND), taking into account the percentage of positive cores.Patients and Methods: Analysis included 1,870 prostate cancer patients who underwent radioisotope-guided sPLND and retropubic radical prostatectomy. Prostate-specific antigen (PSA), clinical T category, primary and secondary biopsy Gleason grade, and percentage of positive cores were included in univariate and multivariate logistic regression models predicting LNI, and constituted the basis for the regression coefficient-based nomogram. Bootstrapping was applied to generate 95% confidence intervals for predicted probabilities. The area under the receiver operator characteristic curve (AUC) was obtained to quantify accuracy.Results: Median PSA was 7.68 ng/ml (interquartile range (IQR) 5.5-12.3). The number of lymph nodes removed was 10 (IQR 7-13). Overall, 352 patients (18.8%) had LNI. All preoperative prostate cancer characteristics differed significantly between LNI-positive and LNI-negative patients (P<0.001). In univariate accuracy analyses, the proportion of positive cores was the foremost predictor of LNI (AUC, 77%) followed by PSA (71.1%), clinical T category (69.9%), and primary and secondary Gleason grade (66.6% and 61.3%, respectively). For multivariate logistic regression models, all parameters were independent predictors of LNI (P<0.001). The nomogram exhibited a high predictive accuracy (AUC, 83.5%).Conclusion: The first update of the only available sentinel nomogram predicting LNI in prostate cancer patients demonstrates even better predictive accuracy and improved calibration. As an additional factor, the percentage of positive cores represents the leading predictor of LNI. This updated sentinel model should be externally validated and compared with results of extended PLND-based nomograms.

Predicting Gleason score using the initial serum total prostate-specific antigen in Black men with symptomatic prostate adenocarcinoma in Nigeria.

BackgroundMen of Black African descent are known to have the highest incidence of prostate cancer. The disease is also more aggressive in this group possibly due to biologically more aggressive tumor or late presentation. Currently, serum prostate-specific antigen (PSA) assay plays a significant role in making the diagnosis of prostate cancer. However, the obtained value of serum PSA may not directly relate with the Gleason score (GS), a measure of tumor aggression in prostate cancer. This study explores the relationship between serum total PSA at presentation (iPSA) and GS.Patients and methodsThe iPSA of patients with histologically confirmed prostate cancer was compared with the obtained GS of the prostate biopsy specimens. The age of the patients at presentation and the prostate volumes were also analyzed with respect to the iPSA and GS. The data were analyzed retrospectively using IBM SPSS Version 20. Pearson correlation was used for numeric variables, whereas Fisher’s exact test was used for categorical variables. Significance was set at P≤0.05.ResultsThere were 205 patients from January 2010 to November 2013 who satisfied the inclusion criteria. iPSA as well as age at presentation and prostate volume were not found to significantly correlate with the primary Gleason grade, the secondary Gleason grade, or the GS. However, the presence of distant metastasis was identified to significantly correlate positively with GS.ConclusionGS may not be confidently predicted by the iPSA. Higher iPSA does not correlate with higher GS and vice versa.

Prediction of clinical progression after radical prostatectomy in a nationwide population-based cohort

Objective: The aim of this study was to create a model for predicting progression-free survival after radical prostatectomy for localized prostate cancer.Material and methods: The risk of biochemical recurrence (BCR) was modelled in a cohort of 3452 men aged 70 years or younger who were primarily treated with radical prostatectomy after being diagnosed between 2003 and 2006 with localized prostate cancer [clinical stage T1c–T2, Gleason score 5–10, N0/NX, M0/MX, prostate-specific antigen (PSA) < 20 ng/ml]. The cohort was split into two: one cohort for model development (n = 3452) and one for validation (n = 1762). BCR was defined as two increasing PSA values of at least 0.2 ng/ml, initiation of secondary therapy, distant metastases or death from prostate cancer. Multivariable Cox proportional hazard regression was applied, predictive performance was assessed using the bootstrap resampling technique to calculate the c index, and calibration of the model was evaluated by comparing predicted and observed Kaplan–Meier 1 year BCR.Results: The overall 5 year progression-free survival was 83% after a median follow-up time of 6.8 years in the development cohort and 7.3 years in the validation cohort. The final model included T stage, PSA level, primary and secondary Gleason grade, and number of positive and negative biopsies. The c index for discrimination between high and low risk of recurrence was 0.68. The probability of progression-free survival ranged from 22% to 97% over the range of risk scores in the study population.Conclusions: This model is based on nationwide population-based data and can be used with a fair predictive accuracy to guide decisions on clinical follow-up after prostatectomy. An online calculator for convenient clinical use of the model is available at www.npcr.se/nomogram

Gleason Score Determination with Transrectal Ultrasound-Magnetic Resonance Imaging Fusion Guided Prostate Biopsies—Are We Gaining in Accuracy?

We evaluated the accuracy of prostate magnetic resonance imaging- transrectal ultrasound targeted biopsy for Gleason score determination. We selected 125 consecutive patients treated with radical prostatectomy for a clinically localized prostate cancer diagnosed on magnetic resonance imaging-transrectal ultrasound targeted biopsy and/or systematic biopsy. On multiparametric magnetic resonance imaging each suspicious area was graded according to PI-RADS™ score. A correlation analysis between multiparametric magnetic resonance imaging and pathological findings was performed. Factors associated with determining the accuracy of Gleason score on targeted biopsy were statistically assessed. Pathological analysis of radical prostatectomy specimens detected 230 tumor foci. Multiparametric magnetic resonance imaging detected 151 suspicious areas. Of these areas targeted biopsy showed 126 cancer foci in 115 patients, and detected the index lesion in all of them. The primary Gleason grade, secondary Gleason grade and Gleason score of the 126 individual tumors were determined accurately in 114 (90%), 75 (59%) and 85 (67%) cases, respectively. Maximal Gleason score was determined accurately in 80 (70%) patients. Gleason score determination accuracy on targeted biopsy was significantly higher for low Gleason and high PI-RADS score tumors. Magnetic resonance imaging-transrectal ultrasound targeted biopsy allowed for an accurate estimation of Gleason score in more than two-thirds of patients. Gleason score misclassification was mostly due to a lack of accuracy in the determination of the secondary Gleason grade.

Gleason Upgrading with Time in a Large Prostate Cancer Active Surveillance Cohort

We report the percentage of patients on active surveillance who had disease pathologically upgraded and factors that predict for upgrading on surveillance biopsies. Patients in our active surveillance database with at least 1 repeat prostate biopsy were included. Histological upgrading was defined as any increase in primary or secondary Gleason grade on repeat biopsy. Multivariate analysis was used to determine baseline and dynamic factors associated with Gleason upgrading. This information was used to develop a nomogram to predict for upgrading or treatment in patients electing for active surveillance. Of 862 patients in our cohort 592 had 2 or more biopsies. Median followup was 6.4 years. Of the patients 20% were intermediate risk, 0.3% were high risk and all others were low risk. During active surveillance 31.3% of cases were upgraded. On multivariate analysis clinical stage T2, higher prostate specific antigen and higher percentage of cores involved with disease at the time of diagnosis predicted for upgrading. A total of 27 cases (15% of those upgraded) were Gleason 8 or higher at upgrading, and 62% of all 114 upgraded cases went on to have active treatment. The nomogram incorporated clinical stage, age, prostate specific antigen, core positivity and Gleason score. The concordance index was 0.61. In this large re-biopsy cohort with medium-term followup, most cases have not been pathologically upgraded to date. A model predicting for upgrading or radical treatment was developed which could be useful in counseling patients considering active surveillance for prostate cancer.

Abstract PR15: The prognostic power of stromal reactivity: An integrated approach to prostate cancer evolution

Abstract Prostate cancer (PCa) is the fifth most common cancer worldwide. Gleason score is the standard metric for defining prostate cancer aggressiveness. Still, prostate cancer is difficult to prognose. Stroma is known to play a major role in tumor progression to malignancy and upon activation (reactive) produces growth factors (GFs) necessary for tissue repair. The prognostic significance of reactive stroma grading in prostate biopsies remains uncertain, except for recurrence in Gleason 7 patients. Moreover, how stromal reactivity and tumor aggressiveness drives progression in PCa remains unclear. To better understand PCa progression, we investigated the interplay between stroma, tumor and microenvironmental heterogeneity in driving PCa aggressiveness. We used an integrated approach combining 7200 simulated prostate cancers over 20 years, 870 prostate cancer patients with 20 years of follow-up (recurrence and death) as well as in-vivo experimentation. We designed a multiscale computational model that incorporates, chemical and physical properties of the microenvironment that modulate the dynamic behavior of hundreds of thousands of cells. This model was simulated on an anatomically reconstructed tissue domain that represents most of the largest segment of the prostate where cancer occurs most frequently (peripheral zone). Each simulated tumor was initiated by seeding a heterogeneous distribution of GF producing tumor cells along with 3 different degrees of reactive stroma. We corroborated our in silico results with whole mount slides from clinical radical prostatectomy specimens. Histopathological analysis included stage, primary and secondary Gleason grades with associated outcomes information. In addition, in vivo experiments were performed combining an initiated epithelial cell line with fibroblasts from patients with pathologically-defined degrees of stromagenesis. The recombinant tissues were grown, stained and the aggressiveness of the tumor was recorded. Our findings reveal that the degree of reactive stroma significantly correlates with the level of aggressiveness of the tumor. Crucially, the degree of stromal reactivity appears to be a significant selection pressure in evolving aggressive tumors. Counter intuitively, a low degree of reactive stroma correlates with a strong selection pressure for higher GF production in the tumor cells - due to the restricted levels of GF found in the microenvironment. This results in a slow progression towards increasingly more aggressive tumor phenotypes. In contrast, a high degree of reactive stroma correlates with a weaker selection pressure for GF producing tumor cells and fast progression - since the GFs are readily accessible to the tumor via the microenvironment. Based on these findings, we conclude that the degree of stromal reactivity is a significant prognostic indicator of recurrence and death for the risk level of low, intermediate and high Gleason grades. For example, Gleason 6 is considered to have a low risk prognosis; however, in cases where the stroma is found to be highly reactive the risk should be considered as high. Patients with Gleason scores 9 or 10 already have a high risk prognosis even when there is a low degree of reactive stroma, but their risk increases even more, when there is a high degree of reactive stroma. In brief, using an integrated computational, experimental and clinical data approach we conclude that the stroma surrounding prostate tumors plays a substantial role in driving PCa evolution toward aggressiveness and prognosis towards higher risk. This abstract is also presented as Poster A66. Citation Format: Ziv Frankenstein, David Basanta, Omar Franco, Douglas Strand, Simon Hayward, Gustavo Ayala, Alexander Anderson. The prognostic power of stromal reactivity: An integrated approach to prostate cancer evolution. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr PR15. doi:10.1158/1538-7445.CHTME14-PR15

Diffusion-Weighted Magnetic Resonance Imaging in the Prostate Transition Zone

The objective of this study was to evaluate the apparent diffusion coefficient (ADC) of diffusion-weighted magnetic resonance (MR) imaging for the differentiation of transition zone cancer from non-cancerous transition zone with and without prostatitis and for the differentiation of transition zone cancer Gleason grade (GG) using MR-guided biopsy specimens as a reference standard. From consecutive MR-guided prostate biopsies (2008-2012) in our referral center, we retrospectively included patients from whom diffusion-weighted MR imaging ADC values were acquired during MR-guided biopsy and whose biopsy cores had a (cancer) core length 10 mm or greater and originated from the transition zone. Two radiologists, who were blinded to the ADC data, annotated regions of interest on biopsy sampling locations of MR-guided biopsy confirmation scans in consensus. Median ADC (mADC) of the regions of interest was related to histopathology outcome in MR-guided biopsy core specimens. Mixed model analysis was used to evaluate mADC differences between 7 histopathology categories predefined as MR-guided biopsy core specimens with primary and secondary GG 4-5 (I), primary GG 4-5 secondary GG 2-3 (II), primary GG 2-3 secondary GG 4-5 (III) and primary and secondary GG 2-3 cancer (IV), and noncancerous tissue without (V) or with degree 1 (VI) or degree 2 prostatitis (VII). Diagnostic accuracy was evaluated using areas under the receiver operating characteristic (AUC) curve. Fifty-two patients with 87 cancer-containing biopsy cores and 53 patients with 101 non-cancerous biopsy cores were included. Significant mean mADC differences were present between cancers (mean mADC, 0.77-0.86 × 10 mm/s) and noncancerous transition zone without (1.12 × 10 mm/s) and with degree 1 to 2 prostatitis (1.05-1.12 × 10 mm/s; P < 0.0001-0.05). Exceptions were mixed primary and secondary GG cancers versus a degree 2 of prostatitis (P = 0.06-0.09). No significant differences were found between subcategories of primary and secondary GG cancers (P = 0.17-0.91) and between a degree 1 and 2 prostatitis and non-cancerous transition zone without prostatitis (P = 0.48-0.94).The mADC had an AUC of 0.84 to differentiate cancer versus non-cancerous transition zone. AUCs of 0.84 and 0.56 were found for mADC to differentiate prostatitis from cancer and from non-cancerous transition zone. The mADC had an AUC of 0.62 to differentiate a primary GG 4 versus GG 3 cancer. The mADC values can differentiate transition zone cancer from non-cancerous transition zone and from a degree 1, and from most cases of a degree 2 prostatitis. However, because of substantial overlap, mADC has a moderate accuracy to differentiate between different primary and secondary GG subcategories and cannot be used to differentiate non-cancerous transition zone from degrees 1 to 2 of prostatitis. Diffusion-weighted imaging ADC may therefore contribute in the detection of transition zone cancers; however, as a single functional MR imaging technique, diffusion-weighted imaging has a moderate diagnostic accuracy in separating higher from lower GG transition zone cancers and in differentiating prostatitis from non-cancerous transition zone.

Development of a nomogram model using a very large sample of patients (pts) to predict the risk of 99mTc-bone scan (BS) positivity in pts receiving androgen deprivation therapy (ADT) for prostate cancer (PCa).

4552 Background: Decisions to start imaging pts with PCa can be difficult due to the heterogeneous nature of the disease. Nomograms can combine information on multiple disease factors to improve predictive accuracy and are not influenced by subjective confounders that may affect clinical judgment. However, currently available nomograms for PCa predict current or future risk of positive BS in ADT-naive pts only. We have developed a new nomogram to predict current BS positivity in ADT-treated pts with PCa using a very large pt sample. Methods: All BS records from 1650 ADT-treated pts who received treatment at the Memorial Sloan-Kettering Cancer Center from 2000 to 2011 were analyzed. Pts were followed up from the start of ADT until the first positive BS or last hospital visit. Multivariate logistic regression analysis was used to model the variables that could be used for predicting likelihood of metastases and the variables were incorporated into the nomogram model. The current probability of bone metastasis was generated by the nomogram using the pt variables at each BS and the predictive accuracy was quantified by calculating the concordance index (C-index). Results: In total, 3949 BS records were analyzed and 950 pts had a positive scan. There was an average of 1.1 prior negative scans before a positive result was recorded. Median prostate-specific antigen (PSA) was 2.5 ng/mL and mean PSA doubling time (PSADT) was 7.8 months. At the same time of the positive scans, 49.4% of pts had a PSA &lt;10 ng/mL. Based on clinical relevance and data availability, 13 variables were included in the nomogram model: number of previous negative BSs, PSA, PSADT, prostatectomy, radiotherapy, brachytherapy, chemotherapy, immunotherapy, estrogen therapy, cryotherapy, clinical trial enrollment, and most recent primary and secondary Gleason grades. C-index for the nomogram was 0.76. Conclusions: This is the first nomogram to predict current BS positivity in pts with PCa following ADT. The nomogram was devised from a very large data set from a single center and provides high predictive accuracy.

Passive bioelectrical properties for assessing high- and low-grade prostate adenocarcinoma

The electrical properties of prostate tissues are dependent on cellular morphology and have been demonstrated to distinguish between benign and malignant formations. Because Gleason grading is also based on tissue architecture we explored the hypothesis that the electrical properties might also provide discriminating power between high- and low-Gleason grade cancers. Electrical properties (σ, ε, Δσ, σ(∞) , f(c) , and α) were gauged from 546 prostate tissue samples and correlated with histopathological assessment. Primary and secondary Gleason grades and a Gleason score were assigned to the tissues identified as cancer. We evaluated how well differently graded cancers were separable from benign tissues and from each other on the basis of these properties using ROC curves. Of the 546 prostate tissue samples, 71 were identified as cancer and 465 as benign. ε, Δσ, σ(∞) , and f(c) provided the most discriminatory power with area under the curves (AUCs) ranging from 0.77-0.82 for detecting any cancer, 0.72-0.8 for low-grade cancer, and increasing to 0.87-0.9 for detecting high-grade cancer. Further, ε, Δσ, and σ(∞) , provided AUCs ranging from 0.74 to 0.75 for discriminating between low- and high-grade cancers. Using the electrical properties to identify prostate cancer is improved when high-grade cancers are sought. These electrical properties can also discriminate between different grades of tumors. These findings suggest that technologies being developed to sense and image these properties in vivo may discriminate between aggressive and indolent lesions.

Predicting 15-Year Prostate Cancer Specific Mortality After Radical Prostatectomy

Long-term prostate cancer specific mortality after radical prostatectomy is poorly defined in the era of widespread screening. An understanding of the treated natural history of screen detected cancers and the pathological risk factors for prostate cancer specific mortality are needed for treatment decision making. Using Fine and Gray competing risk regression analysis we modeled clinical and pathological data, and followup information on 11,521 patients treated with radical prostatectomy at a total of 4 academic centers from 1987 to 2005 to predict prostate cancer specific mortality. The model was validated on 12,389 patients treated at a separate institution during the same period. Median followup in the modeling and validation cohorts was 56 and 96 months, respectively. The overall 15-year prostate cancer specific mortality rate was 7%. Primary and secondary Gleason grade 4-5 (each p<0.001), seminal vesicle invasion (p<0.001) and surgery year (p=0.002) were significant predictors of prostate cancer specific mortality. A nomogram predicting 15-year prostate cancer specific mortality based on standard pathological parameters was accurate and discriminating with an externally validated concordance index of 0.92. When stratified by patient age at diagnosis, the 15-year prostate cancer specific mortality rate for pathological Gleason score 6 or less, 3+4, 4+3 and 8-10 was 0.2% to 1.2%, 4.2% to 6.5%, 6.6% to 11% and 26% to 37%, respectively. The 15-year prostate cancer specific mortality risk was 0.8% to 1.5%, 2.9% to 10%, 15% to 27% and 22% to 30% for organ confined cancer, extraprostatic extension, seminal vesicle invasion and lymph node metastasis, respectively. Only 3 of 9,557 patients with organ confined, pathological Gleason score 6 or less cancer died of prostate cancer. Poorly differentiated cancer and seminal vesicle invasion are the prime determinants of prostate cancer specific mortality after radical prostatectomy. The prostate cancer specific mortality risk can be predicted with remarkable accuracy after the pathological features of prostate cancer are known.

The role of transrectal saturation biopsy in tumour localization: pathological correlation after retropubic radical prostatectomy and implication for focal ablative therapy

• To evaluate the accuracy of an initial 24-core prostate biopsy scheme (PBx24) in predicting unilateral prostate cancer (PCa) in radical prostatectomy (RP) specimens. • Between 2005 and 2008, 203 consecutive patients underwent PBx24 followed by RP for PCa. The area under the curve (AUC) was used to evaluate the accuracy of unilateral PCa on PBx24 to predict unilateral PCa in RP specimens. • The positive predictive value (PPV) and negative predictive value (NPV) were also calculated. Moreover, in patients with unilateral PCa on biopsy, univariable and multivariable logistic regression analyses tested the relationship between the presence of unilateral PCa in an RP specimen and the variables: age, prostate-specific antigen (PSA), total prostate volume, clinical stage, primary Gleason grade, secondary Gleason grade and the number of positive cores. • PCa cores were unilateral in 115 patients (56.7%) on biopsy. Of those, only 26 (22.6%) had unilateral PCa in the RP specimen (AUC, 72.9%; PPV, 22.6%; NPV, 98.8%). In patients with clinically low-risk tumours, only 17 of 63 (27%) had a unilateral PCa on PBx24 and in the RP specimen (AUC, 59.1%; PPV, 27.0%; NPV, 100.0%). • None of the examined variables was an independent predictor of the presence of unilateral PCa in the RP specimen (all P > 0.05). • Initial PBx24 is not sufficiently accurate to be dependable as a method of predicting tumour laterality in RP specimens. Therefore, the use of PBx24 to guide hemi-ablation therapy of PCa may lead to mistreatment in a considerable proportion of patients. • Moreover, none of the routinely available clinical and pathological characteristics appears to improve the ability of unilateral PCa on biopsy to predict unilateral PCa in the RP specimen.

Interobserver and intraobserver reproducibility in digital and routine microscopic assessment of prostate needle biopsies

Advances in whole slide digital imaging in the past decade necessitate validation of these tools in each organ system in advance of clinical adoption. We assessed reproducibility in reporting prostate needle biopsy parameters among urologic pathologists using routine and digital microscopy in a consultation/second opinion-like setting. Four urologic pathologists evaluated a single core level from 50 diagnostically challenging needle biopsy specimens by routine microscopy and whole slide digital imaging. Interobserver and intraobserver agreement were calculated for primary and secondary Gleason grades, Gleason score, tumor quantitation (percentage and size in millimeters), and perineural invasion. Interobserver agreement for routine microscopy was excellent for primary Gleason grade (κ = 0.72) and good for all other parameters (κ ranging from 0.36 to 0.55). Whole slide digital imaging assessment yielded similar agreement for all parameters. Intraobserver agreement for primary Gleason grade and Gleason score was very good to excellent for all pathologists (all κ ≥ 0.65 and ≥ 0.73, respectively). Size of tumor in millimeters consistently displayed higher levels of agreement than percentage of tumor across media and pathologists. Digital assessment of routinely reported cancer parameters on prostatic needle biopsy for a given scanned core level is comparable to that of routine microscopy. These findings imply that histologic interpretation using dynamic whole slide images may accurately simulate routine microscopic evaluation in the consultation setting. Implementation of whole slide digital imaging in these scenarios may significantly reduce the workload of large referral centers in the near future and impact the manner in which pathologists seek second opinion consultation on challenging cases.

2075 PROSTATE CANCER IN RENAL TRANSPLANT RECIPIENTS: BIOPSY COMPLICATIONS AND ONCOLOGIC CHARACTERISTICS

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation, Vascular Surgery I1 Apr 20102075 PROSTATE CANCER IN RENAL TRANSPLANT RECIPIENTS: BIOPSY COMPLICATIONS AND ONCOLOGIC CHARACTERISTICS Sergey S. Ananyev, Rizk El-Galley, and J. Erik Busby Sergey S. AnanyevSergey S. Ananyev More articles by this author , Rizk El-GalleyRizk El-Galley More articles by this author , and J. Erik BusbyJ. Erik Busby More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.2135AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES There are presently no established guidelines for prostate cancer (CaP) screening, detection, and treatment in male renal transplant recipients (RTR). Outcomes for RTR with CaP are varied when compared to non-RTR. Only one previous study has examined the morbidity of biopsy in RTR undergoing evaluation for CaP. We compared a large population of RTR to a non-RTR cohort at a single institution to determine the rate of periprocedural infections from prostate biopsy and subsequent CaP characteristics and outcomes METHODS Of 2,478 RTR from 1993 to 2007, 29 underwent prostate biopsy. Infectious complication was defined as 3 of 4 criteria (T>101F, WBC > 12,000, positive urine culture, positive blood culture), or any criteria coupled with hospitalization. The RTR cohort was compared to 2053 non-RTR men who underwent biopsy in the same period (random sampling of 145 men out of 2053 performed for accurate statistical analysis). Cancer characteristics, treatment, and oncologic outcomes were also compared between the subset of each cohort diagnosed with CaP. RESULTS Of RTR and non-RTR respectively, infectious complication occurred in 10% and 0.7% (p=0.016), and of patients biopsied, CaP was detected in 64% and 46% (p=0.079). Comparing RTR and non-RTR cohorts respectively, mean total Gleason grades were 6.11 and 6.48 (p=0.09), mean primary Gleason grades were 3.06 and 3.18 (p=0.343) and secondary Gleason grades were 3.0 and 3.31 (p=0.042). Treatment for RTR vs non-RTR respectively included active surveillance in 21% and 10%, radiation in 42% and 48%, prostatectomy 32% and 38%, and hormonal ablation 5% and 5%. No difference was seen in the treatment between cohorts (p=0.584). D'Amico risk criteria were low (in 47% versus 48%), intermediate (in 42% versus 36%), and high (in 11% versus 16%) with overall comparable risk distribution (p=0.812) in RTR vs non-RTR. Within African American RTR, there was increased intermediate risk CaP (p=0.003), but otherwise there were no differences among groups. Immunosuppressants did not impact cancer characteristics. CONCLUSIONS Although there is a trend towards increased detection in RTR, the groups have similar CaP risk categories. RTR present with higher secondary Gleason scores and African American RTR have increased intermediate risk CaP. RTR have a significantly increased risk for infectious complications after prostate biopsy, warranting improved measures and patient education. Birmingham, AL© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e807 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sergey S. Ananyev More articles by this author Rizk El-Galley More articles by this author J. Erik Busby More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...