Gleason Upgrading Research Articles

Stability of a 17-Gene Genomic Prostate Score in Serial Testing of Men on Active Surveillance for Early Stage Prostate Cancer.

Genomic testing may improve risk stratification in men with prostate cancer managed by active surveillance. We aimed to characterize the stability and usefulness of serial genomic test scores in men undergoing serial biopsies during active surveillance. We compiled clinical and disease characteristics of men on active surveillance using an institutional Urologic Outcomes Database. We included patients initially diagnosed with Gleason 3 + 3 prostate cancer who elected active surveillance and received 2, 17-gene GPS (Genomic Prostate Score) results. We examined the association of GPS results and Gleason grade reclassification (Gleason 3 + 4 or greater) with definitive treatment using multivariable Cox proportional hazards regression models. We identified 111 men who underwent serial genomic testing. There were 49 grade reclassification events (44%) at a median followup of 64 months. The mean ± SD GPS change between the first and second biopsies was 2.1 ± 10.3. The GPS at first biopsy (per 5 units HR 1.04, 95% CI 1.00-1.07, p=0.03) was associated with an upgrade at second biopsy, although the second GPS was not (HR 1.02, 95% CI 0.99-1.05, p=0.13). The first and second GPSs (HR 1.09, 95% CI 1.04-1.14 and HR 1.09, 95% CI 1.04-1.14, each p <0.01) were associated with active treatment. The GPS undergoes small changes with time. Absolute GPS results at the first and second biopsies were associated with Gleason upgrading and transition from active surveillance to active treatment.

The pathological upgrading after radical prostatectomy in low-risk prostate cancer patients who are eligible for active surveillance: How safe is it to depend on bioptic pathology?

Active surveillance (AS) is one of the treatment alternatives in low-risk prostate cancer (PCa). The pathological upgrading after radical prostatectomy (RP) were investigated in patients who were eligible for AS in the present study. Between August 2006 and July 2017, 627 patients underwent RP in our institution. One hundred and thirty-six patients who were eligible for AS at the time of RP were included in this study. The previously defined AS criteria Gleason 3 + 3=6 adenocarcinoma at maximum two biopsy cores, prostate-specific antigen (PSA) < 10 ng/mL and clinical T stage ≤ 2a were used in the study. The demographics, clinical, and histopathological outcomes were retrospectively compared between two groups, which were divided in accordance with the upgrading status at final pathology as Group 1 (n = 67, upgrading) and Group 2 (n = 69, nonupgrading). Gleason upgrading (GU) was found in 67 (49.3%) patients, and 17 patients (12.5%) were upstaged to pT3a. The upgrading to Gleason 3 + 4 was reported in 38.7% of patients, however, 7.4%, and 3.7% of the patients were upgraded to Gleason 4 + 3, and Gleason 4 + 4, respectively. The 10.3% of the patients had extraprostatic involvement, and the rate (19.4% vs 1.4%, P = .002) was significantly higher in Group 1. PSA density (P = .001), tumor size (P < .001), tumor percentage (P < .001), apical involvement (P = .013), and perineural invasion (P < .001) in RP specimen were higher in Group 1. Multivariate analysis showed that perineural invasion (OR = 4.26; 95%CI: 1.76-10.33; P = .001) and pathologic T stage (OR = 5.45; 95%CI: 1.08-27.4; P = .04) were independently associated with GU. Since 12.5% of the patients upstaged to pT3a disease, and there is a possible risk of Gleason 4 pattern, upgrading of the tumor should carefully be kept in mind before offering AS to low-risk patients with PCa.

Neutrophil, Platelets, and Eosinophil to Lymphocyte Ratios Predict Gleason Score Upgrading in Low-Risk Prostate Cancer Patients

Background: Several biochemical and clinical markers have been proposed for selecting patients for active surveillance (AS). However, some of these are expensive and not easily accessible. Moreover, currently about 30% of patients on AS harbor aggressive disease. Hence, there is an urgent need for other tools to accurately identify patients with low-risk prostate cancer (PCa). Patients: We retrospectively reviewed the medical records of 260 patients who underwent radical prostatectomy and were eligible for AS according to the following criteria: clinical stage T2a or less, prostate-specific antigen level < 10 ng/mL, 2 or fewer cores involved with cancer, Gleason score (GS) ≤6 grade, and prostate-specific antigen density < 0.2 ng/mL/cc. Methods: Univariate and multivariate analyses were performed to evaluate the association of patient and tumor characteristics with reclassification, defined as upstaged (pathological stage >pT2) and upgraded (GS ≥7) disease. A base model (age, prostate-specific antigen, prostate volume, and clinical stage) was compared with models considering neutrophil to lymphocyte ratio (NLR) or platelets to lymphocyte ratio (PLR), monocyte to lymphocyte (MLR), and eosinophil to lymphocyte ratio (ELR). OR and 95% CI were calculated. Finally, a decision curve analysis was performed. Results: Univariate and multivariate analyses showed that NLR, PLR, and ELR upgrading were significantly associated with upgrading (ORs ranging from 2.13 to 4.13), but not with upstaging except for MLR in multivariate analysis, showing a protective effect. Conclusion: Our results showed that NLR, PLR, and ELR are predictors of Gleason upgrading. Therefore, these inexpensive and easily available tests might be useful in the assessment of low-risk PCa, when considering patients for AS.

Prostate Cancers Detected by Magnetic Resonance Imaging-Targeted Biopsies Have a Higher Percentage of Gleason Pattern 4 Component and Are Less Likely to Be Upgraded in Radical Prostatectomies.

In Gleason score (GS) 7 prostate cancers, the quantity of Gleason pattern 4 (GP 4) is an important prognostic factor and influences treatment decisions. Magnetic resonance imaging (MRI)-targeted biopsy has been increasingly used in clinical practice. To investigate whether MRI-targeted biopsy may detect GS 7 prostate cancer with greater GP 4 quantity, and whether it improves biopsy/radical prostatectomy GS concordance. A total of 243 patients with paired standard and MRI-targeted biopsies with cancer in either standard or targeted or both were studied, 65 of whom had subsequent radical prostatectomy. The biopsy findings, including GS and tumor volume, were correlated with the radical prostatectomy findings. More prostate cancers detected by MRI-targeted biopsy were GS 7 or higher. Mean GP 4 percentage in GS 7 cancers was 31.0% ± 29.3% by MRI-targeted biopsy versus 25.1% ± 29.5% by standard biopsy. A total of 122 of 218 (56.0%) and 96 of 217 (44.2%) prostate cancers diagnosed on targeted biopsy and standard biopsy, respectively, had a GP 4 of 10% or greater ( P = .01). Gleason upgrading was seen in 12 of 59 cases (20.3%) from MRI-targeted biopsy and in 24 of 57 cases (42.1%) from standard biopsy ( P = .01). Gleason upgrading correlated with the biopsy cancer volume inversely and GP 4 of 30% or less in standard biopsy. Such correlation was not found in MRI-targeted biopsy. Magnetic resonance imaging-targeted biopsy may detect more aggressive prostate cancers and reduce the risk of Gleason upgrading in radical prostatectomy. This study supports a potential role for MRI-targeted biopsy in the workup of prostate cancer and inclusion of percentage of GP 4 in prostate biopsy reports.

Cumulative Cancer Locations is a Novel Metric for Predicting Active Surveillance Outcomes: A Multicenter Study

BackgroundActive surveillance (AS) of prostate cancer (PC) has increased in popularity to address overtreatment. ObjectiveTo determine whether a novel metric, cumulative cancer locations (CCLO), can predict AS outcomes in a group of AS patients with low and very low risk. Design, setting, and participantsCCLO is obtained by summing the total number of histological cancer-positive locations in both diagnostic and confirmatory biopsies (Bx). The retrospective study cohort comprised three prospective AS cohorts (Helsinki University Hospital: n=316; European Institute of Oncology: n=204; and University of Münster: n=89). Outcome measurements and statistical analysisWe analyzed whether risk stratification based on CCLO predicts different AS outcomes: protocol-based discontinuation (PBD), Gleason upgrading (GU) during AS, and adverse findings in radical prostatectomy (RP) specimens. ResultsIn Kaplan Meier analyses, patients in the CCLO high-risk group experienced significantly shorter event-free survival for all outcomes (PBD, GU, and adverse RP findings; all p<0.002). In multivariable Cox regression analysis, patients in the CCLO high-risk group had a significantly higher risk of experiencing PBD (hazard ratio [HR] 12.15, 95% confidence interval [CI] 6.18–23.9; p<0.001), GU (HR 6.01, 95% CI 2.16–16.8; p=0.002), and adverse RP findings (HR 9.144, 95% CI 2.27–36.9; p=0.006). In receiver operating characteristic analyses, the area under the curve for CCLO outperformed the number of cancer-positive Bxs in confirmatory Bx in predicting PBD (0.734 vs 0.682), GU (0.655 vs 0.576) and adverse RP findings (0.662 vs 0.561) and the added value was supported by decision curve analysis. ConclusionsCCLO is distinct from the number of positive Bx cores. Higher CCLO predicts AS outcomes and may aid in selection of patients for AS. Patient summaryFor patients on active surveillance for prostate cancer, the cumulative number of cancer-positive locations in diagnostic and confirmatory biopsies is a predictor of active surveillance outcomes.

MP05-19 THE FACTORS ASSOCIATED WITH GLEASON UPGRADING AT RADICAL PROSTATECTOMY: A PERSPECTIVE FROM THE SINGLE INSTITUTIONAL ASSESSMENT OF BIOPSY AND FINAL PATHOLOGY

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy I1 Apr 2018MP05-19 THE FACTORS ASSOCIATED WITH GLEASON UPGRADING AT RADICAL PROSTATECTOMY: A PERSPECTIVE FROM THE SINGLE INSTITUTIONAL ASSESSMENT OF BIOPSY AND FINAL PATHOLOGY Selcuk Erdem, Samed Verep, Tzevat Tefik, Yasemin Ozluk, Isin Kilicaslan, Murat Tunc, Oner Sanli, Ismet Nane, and Faruk Ozcan Selcuk ErdemSelcuk Erdem More articles by this author , Samed VerepSamed Verep More articles by this author , Tzevat TefikTzevat Tefik More articles by this author , Yasemin OzlukYasemin Ozluk More articles by this author , Isin KilicaslanIsin Kilicaslan More articles by this author , Murat TuncMurat Tunc More articles by this author , Oner SanliOner Sanli More articles by this author , Ismet NaneIsmet Nane More articles by this author , and Faruk OzcanFaruk Ozcan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.190AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Gleason upgrading (GU) at radical prostatectomy (RP) is a concern in the prostate cancer (PCa) treatment. This study aims to investigate which clinical and histopathologic factors are associated to GU at RP. METHODS Between January 2005-September 2017, 694 RPs were performed in our department. After excluding 21 RPs with incomplete records, 673 RPs were included in this study and divided into two groups: Group 1 (Upgrading) and Group 2 (No Upgrading). A subgroup of 443 patients whose biopsy were examined by only our institutional pathology department were divided by same grouping. The retrospectively collected clinical and histopathological parameters were compared between two groups. Chi square and Mann-Whitney U tests were used to compare categorical and non-parametric continuous parameters, respectively. Logistic regression was used for multivariate analysis. RESULTS The analyses of overall and subgroup cohorts found that PSA level (p=0.001, p=0.005) and pathologic tumor size (p<0.001, p<0.001) were increased while pathologic prostate weight (p=0.001, p=0.006) was decreased in Group 1. The biopsy report from external institution (p<0.001) was higher in Group 1 at the comparison of overall cohort. The rates of pT3 stage (p<0.001, p<0.001), extraprostatic disease (p<0.001, p=0.001), perineural invasion (p<0.001, p<0.001), apical (p=0.001, p=0.001) and bladder neck (p=0.017, p=0.007) involvement were higher in Group 1 at two comparisons. Multivariate analyses showed that the independent factors associated with GU after RP were perineural invasion (p<0.001), biopsy report of external institution (p<0.001) and pathologic tumor size (p=0.001) at overall cohort meanwhile perineural invasion (p=0.001), pathologic tumor size (p=0.034) and apical involvement (p=0.044) at subgroup cohort. CONCLUSIONS Single institutional assessment of bioptic and final pathologies may reduce GU reports at RP. However it plays a marginal role to define independent factors associated with GU. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e50-e51 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Selcuk Erdem More articles by this author Samed Verep More articles by this author Tzevat Tefik More articles by this author Yasemin Ozluk More articles by this author Isin Kilicaslan More articles by this author Murat Tunc More articles by this author Oner Sanli More articles by this author Ismet Nane More articles by this author Faruk Ozcan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Biparametric Prostate Imaging Reporting and Data System version2 and International Society of Urological Pathology Grade Predict Biochemical Recurrence after RadicalProstatectomy.

We retrospectively assessed the clinical significance of the Prostate Imaging Reporting and Data System (PI-RADS), version 2, criteria based on biparametric magnetic resonance imaging (bp-MRI), together with the International Society of Urological Pathology (ISUP) grade, for predicting biochemical recurrence (BCR) after radical prostatectomy. The data from 126 patients who had undergone radical prostatectomy were retrospectively analyzed. The prognostic significance of the PI-RADS v2 score based on bp-MRI was assessed with other clinical factors, including the ISUP grade. We defined a positive PI-RADS and ISUP score as≥ 4 and≥ 3, respectively. Statistical analysis was performed using Cox proportional hazard models, logistic regression analysis, and the Kaplan-Meier method. The median age and median prostate-specific antigen level were 66 years and 7.96 ng/mL, respectively. The number of positive PI-RADS scores was 106 (84.1%) and the number of positive ISUP grade scores was 71 (56.3%). PI-RADS≥ 4 (P= .0031) and ISUP≥ 3 (P= .070) were the 2 independent prognostic factors predictive of BCR. A positive PI-RADS score was related to tumor volume (P= .014), and a positive ISUP score was related to prostate-specific antigen level (P= .043), extraprostatic extension (P= .029), and Gleason upgrading (P< .0001). After stratifying patients into risk groups according to PI-RADS and ISUP positivity, the poor-risk group (PI-RADS and ISUP grade positive) showed significantly worse BCR-free survival compared with that of the favorable- and intermediate-risk groups (P< .0001), with a median survival difference of 21 months. Biparametric PI-RADS v2 and ISUP grade criteria predicted for BCR after radical prostatectomy. PI-RADS v2 combined with the ISUP grade might be helpful in choosing the treatment modality of patients with localized prostate cancer.

Outcomes of serial MRI/ultrasound fusion targeted biopsy in men with very low-risk and low-risk prostate cancer managed with active surveillance.

114 Background: The utility of serial magnetic resonance imaging (MRI)/ultrasound (US) fusion targeted prostate biopsy in men with prostate cancer (PCa) on active surveillance (AS) have not been clearly defined. We sought to investigate the rate of Gleason upgrading both on sequential fusion targeted and systematic biopsies among men with low-risk PCa managed with AS. Methods: We retrospectively queried an institutional database of 800 patients undergoing MRI/US fusion biopsy to identify 209 patients on AS with at least two fusion biopsies between December 2013 and November 2016. Men with National Comprehensive Cancer Network (NCCN) very low-risk and low-risk criteria were included. Gleason upgrade was defined as detection of Gleason score &gt;=3+4. The proportion of patients experiencing upgrade on systematic, fusion, or both biopsy techniques was tabulated. Associations of clinical, pathologic, and imaging factors with biopsy upgrade were analyzed by logistic regression. Results: Of 209 patients undergoing MRI/US fusion biopsy, 73 (35.0%) had at least two targeted biopsies (66% very low-risk and 34% low-risk PCa). The time between biopsies was 12.6 months (11.2-17.7). The median PSA and PSA density were 5.4 ng/mL (4.2-7.1) and 0.11 ng/mL/mL (0.07-0.18), respectively. 21 (29%) patients experienced Gleason upgrade on subsequent biopsy. Of those, 6 (8%), 5 (7%), and 10 (14%) had upgrade on systematic biopsy only, fusion biopsy only, and both systematic and fusion biopsy, respectively. Patients with upgrade on subsequent biopsy had higher PSA (p=0.02) and PSA density (p=0.02), and were among low-risk disease population (p=0.03). In logistic regression models, greater number of positive cores in systematic biopsy (OR 1.88; 95% CI 1.23-2.92; p=0.005) was associated with the total Gleason upgrade on repeated biopsy. Conclusions: In men with favorable risk prostate cancer managed with AS, Gleason upgrade was detected in a 29% of patients on a second MRI/US fusion biopsy including both targeted and systematic regions. These findings support the continued use of both MRI fusion and systematic biopsy during surveillance due to risks of reclassification over time.

Heterogeneity in early oncologic outcomes among men with NCCN intermediate-risk prostate cancer treated with radical prostatectomy.

144 Background: The National Comprehensive Cancer Network (NCCN) risk classification scheme for prostate cancer (PCa) encompasses several definitions and has been shown to contain significant heterogeneity. Because patients possessing a single intermediate-risk (IR) feature may be regarded as ineligible for active surveillance (AS), we aimed to compare pathologic and early oncologic outcomes between those with low-risk (LR) and IR features based on the number of criteria met. Methods: We queried the National Cancer Database (NCDB) to identify men with NCCN LR (cT1-T2a, prostate-specific antigen [PSA] &lt; 10 ng/mL, and Gleason score (GS)≤6) and IR PCa diagnosed from 2010-2014 who were treated with radical prostatectomy (RP). Patients with IR PCa were stratified based on a single factor: clinical stage (cT2b-T2c), PSA (10-20 ng/mL), GS 3+4, or GS 4+3 alone. The pathologic outcomes including any Gleason upgrade, and adverse pathology (primary Gleason 4 or ≥pT3 at RP), and receipt of adjuvant radiation therapy (RT) were compared between the LR and IR groups. Odds ratios for pathologic outcomes and receipt of adjuvant RT were computed using logistic regression analyses. Results: Of 181,847 men treated with RP, we identified 30.7% and 37.1% with LR and IR PCa, respectively. Of 67,623 with IR PCa, 4,075 (6%) were due to clinical stage alone, 5,004 (7.4%) by PSA, 43,409 (64.2%) by GS 3+4, and 15,135 (22.4%) by GS 4+3. Patients meeting IR by clinical stage alone had similar risks of adverse pathology as LR patients (OR 1.03, 95%CI 0.94-1.13, p = 0.49). In contrast, those meeting IR by PSA alone had higher risks of adverse pathology compared with LR individuals (OR 2.20, 95%CI 2.05-2.36, p &lt; 0.001). Moreover, receipt of adjuvant RT was similar among LR and IR patients by clinical stage alone (p = 0.62), and higher among patients meeting IR by PSA alone (OR 2.99, 95% CI 2.43-3.69, p &lt; 0.001). Conclusions: Based on national cancer registry data, early outcomes among men meeting the NCCN IR definition for PCa are heterogeneous. IR patients by clinical stage alone had similar rates of adverse pathology as did LR group. Broadened eligibility for AS should be considered to include those meeting favorable IR definitions.

Risk of Upgrading from Prostate Biopsy to Radical Prostatectomy Pathology—Does Saturation Biopsy of Index Lesion during Multiparametric Magnetic Resonance Imaging-Transrectal Ultrasound Fusion Biopsy Help?

We sought to determine whether saturation of the index lesion during magnetic resonance imaging-transrectal ultrasound fusion guided biopsy would decrease the rate of pathological upgrading from biopsy to radical prostatectomy. We analyzed a prospectively maintained, single institution database for patients who underwent fusion and systematic biopsy followed by radical prostatectomy in 2010 to 2016. Index lesion was defined as the lesion with largest diameter on T2-weighted magnetic resonance imaging. In patients with a saturated index lesion transrectal fusion biopsy targets were obtained at 6 mm intervals along the long axis of the index lesion. In patients with a nonsaturated index lesion only 1 target was obtained from the lesion. Gleason 6, 7 and 8-10 were defined as low, intermediate and high risk, respectively. Included in the study were 208 consecutive patients, including 86 with a saturated and 122 with a nonsaturated lesion. Median patient age was 62.0 years (IQR 10.0) and median prostate specific antigen was 7.1 ng/ml (IQR 8.0). The median number of biopsy cores per index lesion was higher in the saturated lesion group (4 vs 2, p <0.001). The risk category upgrade rate from systematic only, fusion only, and combined fusion and systematic biopsy results to prostatectomy was 40.9%, 23.6% and 13.8%, respectively. The risk category upgrade from combined fusion and systematic biopsy results was lower in the saturated than in the nonsaturated lesion group (7% vs 18%, p = 0.021). There was no difference in the upgrade rate based on systematic biopsy between the 2 groups. However, fusion biopsy results were significantly less upgraded in the saturated lesion group (Gleason upgrade 20.9% vs 36.9%, p = 0.014 and risk category upgrade 14% vs 30.3%, p = 0.006). Our results demonstrate that saturation of the index lesion significantly decreases the risk of upgrading on radical prostatectomy by minimizing the impact of tumor heterogeneity.

Clinical Variables That Predict for Adverse Pathological Features in Intermediate Risk Prostate Cancer

Significant clinical heterogeneity exists in man with intermediate risk prostate cancer (IRP). Precise risk stratification may aid optimal management recommendation. The present study was conducted to evaluate risk of up-grading and adverse pathological features with a larger cohort of patients. Patients with IRP, as defined by NCCN guideline, were included in this study. Men with unfavorable IRP included any IRP with a primary Gleason score (GS) of 4, percentage of positive biopsy cores >=50%, or multiple intermediate risk factors. Clinical and pathological reports from 1560 patients with IRP who underwent radical prostatectomy (RP) at our institution were reviewed and analyzed. The rates of pathologic Gleason upgrade (GU), and adverse pathological features (defined as extracapsular extension, seminal vesicle invasion, positive surgical margins, or positive lymph node involvement) were reported. Chi-square tests were used to assess differences in categorical variables and t-tests for continuous variables between groups. Multivariable logistic regression analysis was used to determine clinical factors that significantly predicted for adverse pathological outcomes. A total of 329 (21.1%) and 650 (41.7%) of patients had GU or adverse pathologic features at the time of RP, respectively. Patients with GU were older (p<0.001), had a higher preoperative PSA (p<0.001), and lower GS on biopsy (p<0.001). Patients with adverse pathologic features were older (p<0.001), had a higher preoperative PSA (p<0.001), higher GS on biopsy (p<0.001), higher clinical T stage (p<0.001), higher percent positive cores on biopsy (38.2% vs. 29.6%, p<0.001), higher percent positive perineural invasion on biopsy (17.9% vs. 9.1%, p<0.001), and a higher incidence of unfavorable IRP (66.3% vs. 48.8%, p<0.001). Race was not a significant risk factor for any of these adverse pathological outcomes. On multivariable analysis, increasing PSA level, older age, biopsy GS, and unfavorable intermediate risk category were statistically significantly associated with GU and adverse pathologic features. An increased percent positivity of cancer on core was associated with adverse pathologic features. Based on our single institution experience, we have identified key clinical variables that are associated with GU and adverse pathological features in patients with IRP. These are important considerations when planning for optimal treatment for this cohort of patients.

Machine Learning to Predict Postradical Prostatectomy Pathology Outcomes in Intermediate Risk Prostate Cancer

Intermediate risk prostate cancer (IRPC) is a heterogeneous disease with various treatment options. Existing efforts to further risk stratify this disease entity were developed using a small a priori determined subset of predictors. Here, we use statistical machine learning that pulls from a larger pool of demographics and clinical features to better predict post-radical prostatectomy (RP) pathologic outcomes in IRPC. Knowing the probability of high risk pathology and thus the likelihood of adjuvant radiation may inform patients deciding between upfront surgery and radiation. We retrospectively reviewed patients who underwent RP from 6/2005 to 5/2015 at our institution and included 1560 patients with clinical IRPC, defined per NCCN. Predictors included demographics, PSA and location-specific biopsy findings. The post-RP surgical pathology variables analyzed were positive margins, Gleason upgrading and pathologic upstaging.MATLAB was used. We imputed missing data and used minority oversampling to balance data. 69 predictors were eligible after pre-processing. We used a combination of feature selection methods to decrease multicollinearity and overfitting. Learning methods included logistic regression (LR) with or without lasso regularization and support vector machine with a Gaussian kernel (SVM) with or without forward feature selection. 10-fold cross validation was used to estimate the performance of our model building methods. Statistical measures are reported with syntax: sensitivity/specificity/positive predictive value (PPV)/negative predictive value (NPV). Positive margins: SVM had excellent results with 98%/95%/95%/98% (AUC ∼1.0). Feature selection chose 11 predictors with 71%/75%/74%/72% (AUC 0.83). LR with or without lasso had poorer outcomes except specificity and NPV with <10%/99%/<34%/87%.Gleason upgrading: SVM performance was again excellent with 95%/89%/90%/95% (AUC 0.97). Feature selection narrowed to 21 predictors with good performance at 85%/73%/75%/83% (AUC 0.87). LR was inferior except in specificity with 24%/93%/47%/82% (AUC 0.68). Lasso selected 6 features with 6%/100%/100%/80% (AUC 0.73).Pathologic upstaging: SVM again was superior except for specificity, with 79%/77%/77%/79% (AUC 0.85). Feature selection resulted in 30 variables with 74%/74%/73%/75% (AUC 0.82). Using LR with or without lasso (39 features) resulted in almost identical performance with 50%/84%/65%/74% (AUC 0.73). We are able to build statistical machine learning models of varying complexity to accurately estimate post-RP pathological outcomes. While overall SVM performance was superior—likely due to its ability to handle high dimensional data—LR had unique advantages, suggesting that an ensemble method may be optimal. Further development of these models, including deep learning, may allow us to inform patients and colleagues whether upfront surgery or radiation would be the optimal choice.

Impact of 5α-Reductase Inhibitors on Disease Reclassification among Men on Active Surveillance for Localized Prostate Cancer with Favorable Features

We determined the effect of 5α-reductase inhibitors on disease reclassification in men with prostate cancer optimally selected for active surveillance. In this retrospective review we identified 635 patients on active surveillance between 2002 and 2015. Patients with favorable cancer features on repeat biopsy, defined as absent Gleason upgrading, were included in the cohort. Patients were stratified by those who did or did not receive finasteride or dutasteride within 1 year of diagnosis. The primary end point was grade reclassification, defined as any increase in Gleason score or predominant Gleason pattern on subsequent biopsy. This was assessed by multivariable Cox proportional hazards regression analysis. At diagnosis 371 patients met study inclusion criteria, of whom 70 (19%) were started on 5α-reductase inhibitors within 12 months. Median time on active surveillance was 53 vs 35 months in men on vs not on 5α-reductase inhibitors (p<0.01). Men on 5α-reductase inhibitors received them for a median of 23 months (IQR 6-37). On actuarial analysis there was no significant difference in grade reclassification for 5α-reductase inhibitor use in patients overall or in the very low/low risk subset. The overall percent of patients who experienced grade reclassification was similar at 13% vs 14% (p = 0.75). After adjusting for baseline clinicopathological features 5α-reductase inhibitors were not significantly associated with grade reclassification (HR 0.80, 95% CI 0.31-1.80, p = 0.62). Furthermore, no difference in adverse features on radical prostatectomy specimens was observed in treated patients (p = 0.36). Among our cohort of men on active surveillance 5α-reductase inhibitor use was not associated with a significant difference in grade reclassification with time.

History of PSA screening on prostate cancer aggressiveness.

5066 Background: In 2012, PSA screening for prostate cancer (CaP) detection was given a “Grade D” recommendation for all men by the USPSTF. Recent U.S. studies report declines in PSA screening with concomitant increases in advanced CaP at diagnosis. This study examined the association between PSA screening history and CaP aggressiveness in a racially diverse, military cohort with equal health care access. Methods: This retrospective cohort study evaluated CaP patients undergoing radical prostatectomy (RP) from 1994-2015 at Walter Reed National Military Medical Center. Whole-mounted prostatectomy specimens were classified using 2014 ISUP Gleason grading system. Excluding the diagnostic PSA, screening history was categorized as: ≥ 6 PSA’s prior to CaP diagnosis (uppermost quartile), 1-5 (lower 3 quartiles), vs. no screening history. Multivariable logistic regression (MLR) was used to examine NCCN risk stratum (intermediate-high vs. low) and Gleason upgrade (GU) from biopsy to RP. Multivariable Cox proportional hazards (Cox PH) analyses were used to model time to biochemical recurrence (BCR). Multivariable models controlled for age at RP, race, family history and obesity (BMI &gt; 30 vs. ≤ 30 kg/m2). The GU and BCR models also controlled for NCCN risk classification. Results: There were 1,772 eligible patients with a median follow-up and age at RP of 7.0 and 59.8 years, respectively. Prior to CaP diagnosis, 42% and 19% of men had 1-5 and ≥ 6 PSA’s screenings, respectively. MLR showed greater odds of intermediate or high vs. low risk disease for PSA screening history of none vs. 1-5 (OR = 1.33, CI = 1.03-1.70, p = 0.028) but not for none vs. ≥ 6 (p = 0.44). MLR showed increased odds of GU for none vs. ≥ 6 (OR = 1.81, CI = 1.23-2.7, p &lt; 0.001). Multivariable Cox PH models showed incrementally poorer BCR-free survival as screening history decreased (HRNone vs. ≥6 = 2.27, CI = 1.54-3.33, p &lt; 0.001; HRNone vs. 1-5= 1.49, CI = 1.15-1.92, p = 0.002). Conclusions: In this RP cohort, higher risk stratum, increased GU, and poorer BCR-free survival were associated with no PSA screening history. BCR-free survival was incrementally worsened by less PSA screening. A complete absence of PSA screening may lead to more aggressive disease at presentation and poorer clinical outcomes.

Population-based study of grade progression in patients who harboured Gleason 3+3.

This study aimed to evaluate (1) the time interval between a decision to commence on active surveillance (AS) and grade progression in community practice; (2) factors predicting grade progression in localised prostate cancer (CaP) patients apparently undergoing AS. Data from the Prostate Cancer Outcomes Registry-Victoria were used to analyze men with Gleason 3+3 CaP or less who had at least one repeat biopsy. Unadjusted and adjusted 5-year Kaplan-Meier survival curves were used to assess the time to grade progression. Both univariate and multivariate analyses for grade progression were performed using Cox proportional hazards. The cohort included 951 men. Overall, 39% of men had Gleason grade reclassified to a higher risk disease state with median of 2.2years [IQR 1.2-3.7years]. Men who harboured cT2 disease were 30% more likely to have upgrading compared to men with cT1 disease (adjusted HR: 1.3, 95% CI 1.0-1.6, p=0.048). Half of the men with cT2 in our cohort had their Gleason grade reclassified within 1.6years from diagnosis as compared with 2.7years for the cT1 group. The presence of percentage of core involvement >25.0% and a PSA velocity of >1.01ng/mL/year remained significant for a higher progression rate. The adjusted HR: 1.6; 95% CI [1.2-2.3], p=0.004; adjusted HR: 1.6, 95% CI [1.2-2.4], p=0.021, for percent of core involvement of 25.1-37.5%, and ≥37.6%, respectively. The adjusted HRs and p value associated with PSA velocity were 1.5; 95% CI [1.1-2.1], p=0.016 and 1.6; 95% CI [1.2-2.3], p=0.003 for PSA velocity values of 1.01-2ng/mL per year and >2ng/mL per year, respectively. Men who were diagnosed in regional hospital and subsequently had biopsy in metropolitan hospital were twice at risk of having Gleason upgrade compared to those whom both diagnostic and surveillance biopsies were carried out in metropolitan hospitals (adjusted HR: 1.9; 95% CI 1.1-3.3, p=0.029). When placing men on AS and considering time to histologic progression, clinicians should pay particular attention to the likely accuracy of the diagnostic specimen, their tumour stage, volume of tumour (percent of core involvement), and rising PSA. Those diagnosed with T2 disease and had >25.0% of core involvement, and a PSA velocity greater than 1ng/mL per year is at particular risk for more rapid disease progression and, for this reason, should be counselled on the importance of following the recommended surveillance regimen. For half of these men, their disease will have 'progressed' according to biopsy results in 2 years.

PD61-04 COMPARISON OF GLEASON UPGRADING RATES IN TRANSRECTAL ULTRASOUND SYSTEMATIC RANDOM BIOPSIES VERSUS US-MRI FUSION BIOPSIES FOR PROSTATE CANCER.

You have accessJournal of UrologyProstate Cancer: Staging II1 Apr 2017PD61-04 COMPARISON OF GLEASON UPGRADING RATES IN TRANSRECTAL ULTRASOUND SYSTEMATIC RANDOM BIOPSIES VERSUS US-MRI FUSION BIOPSIES FOR PROSTATE CANCER. Arie Carneiro, Paulo Kayano, Tiago Castilho, Arjun Sivaraman, Oliver Claros, Ary Neto, Renee Filippi, Ronaldo Baroni, and Gustavo Lemos Arie CarneiroArie Carneiro More articles by this author , Paulo KayanoPaulo Kayano More articles by this author , Tiago CastilhoTiago Castilho More articles by this author , Arjun SivaramanArjun Sivaraman More articles by this author , Oliver ClarosOliver Claros More articles by this author , Ary NetoAry Neto More articles by this author , Renee FilippiRenee Filippi More articles by this author , Ronaldo BaroniRonaldo Baroni More articles by this author , and Gustavo LemosGustavo Lemos More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2763AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES US-MRI fusion biopsy (FB) showed that it improves the detection of clinically significant prostate cancer (PCa). A more accurate diagnostic method is desirable to avoid misclassification, which in turn is particularly important in appropriate decision making on treatment for PCa (active surveillance or focal therapy or radical treatment). We aimed to compare the Gleason upgrading (GU) rates and the concordance of the Gleason scores in the biopsy versus final pathology after the surgery in patients who underwent only TRUS systematic random biopsies versus US-MRI FB for PCa. METHODS A retrospective analysis of patients′ prospective collected data that underwent prostate biopsy and subsequent radical prostatectomy were included from January 2011 to June 2016 at our institution. The study cohort was divided into: US-MRI FB (Group A) and only TRUS systematic random biopsy (Group B). US-MRI FB was performed in patients who had a previous MRI with a focal lesion classified by Likert score ≥ 3, otherwise a TRUS systematic random biopsy was performed. All biopsies and surgical specimens were analyzed by the same uropathologist and MRIs were analyzed by two expert urological radiologists. RESULTS 73 men underwent US-MRI FB and 89 TRUS systematic random biopsy. The GU rate was higher in group B (31.5% vs 16.4%; p = 0.027). GU according to Gleason grade pattern was higher in Group B against Group A (40.4% vs 23.3%; p = 0.02). Analyses from separate Gleason grade pattern showed that Gleason score 3+4 presented less GU in group A (24.1% vs 52.6%; p = 0.043)(table 1). The Bland-Altman plot analysis showed a higher bias in Group B compared to group A (-0.27 [-1.40 to 0.86] vs -0.01 [-1.42 to 1.39]). In the multivariable logistic regression the only independent predictor of GU was the use of TRUS systematic random biopsy (2.64 [1.11 - 6.28]; p = 0.024). CONCLUSIONS The US-MRI FB appears to be related to a decrease in GU rate and an increase in the concordance between biopsy and final pathology in comparison to TRUS random biopsy, that leads to greater accuracy on diagnosis and better treatment decision. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1188-e1189 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Arie Carneiro More articles by this author Paulo Kayano More articles by this author Tiago Castilho More articles by this author Arjun Sivaraman More articles by this author Oliver Claros More articles by this author Ary Neto More articles by this author Renee Filippi More articles by this author Ronaldo Baroni More articles by this author Gustavo Lemos More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Pathologic correlation of transperineal in-bore 3-Tesla magnetic resonance imaging-guided prostate biopsy samples with radical prostatectomy specimen.

To determine the accuracy of in-bore transperineal 3-Tesla (T) magnetic resonance (MR) imaging-guided prostate biopsies for predicting final Gleason grades in patients who subsequently underwent radical prostatectomy (RP). A retrospective review of men who underwent transperineal MR imaging-guided prostate biopsy (tpMRGB) with subsequent radical prostatectomy within 1 year was conducted from 2010 to 2015. All patients underwent a baseline 3-T multiparametric MRI (mpMRI) with endorectal coil and were selected for biopsy based on MR findings of a suspicious prostate lesion and high degree of clinical suspicion for cancer. Spearman correlation was performed to assess concordance between tpMRGB and final RP pathology among patients with and without previous transrectal ultrasound (TRUS)-guided biopsies. A total of 24 men met all eligibility requirements, with a median age of 65 years (interquartile range [IQR] 11.7). The median time from biopsy to RP was 85 days (IQR 50.5). Final pathology revealed Gleason 3+4=7 in 12 patients, 4+3=7 in 10 patients, and 4+4=8 in 2 patients. A strong correlation (ρ: +0.75, p<0.001) between tpMRGB and RP results was observed, with Gleason scores concordant in 17 cases (71%). 16 of the 24 patients underwent prior TRUS biopsies. Subsequent tpMRGB revealed Gleason upgrading in 88% of cases, which was concordant with RP Gleason scores in 69% of cases (ρ: +0.75, p<0.001). Final Gleason scores diagnosed by tpMRGB at 3-T correlate strongly with final RP surgical pathology. This may facilitate prostate cancer diagnosis, particularly in patients with negative or low-grade TRUS biopsy results in whom clinically significant cancer is suspected or detected on mpMRI.

795 - PTEN status in diagnostic biopsies predicts active surveillance rebiopsy Gleason upgrade, treatment change and adverse surgical histopathological findings

795 - PTEN status in diagnostic biopsies predicts active surveillance rebiopsy Gleason upgrade, treatment change and adverse surgical histopathological findings

Comparison of Gleason upgrading rates in transrectal ultrasound systematic random biopsies versus US-MRI fusion biopsies for prostate cancer.

57 Background: US-MRI fusion biopsy (FB) showed that it improves the detection of clinically significant prostate cancer (PCa). A more accurate diagnostic method is desirable to avoid misclassification, which in turn is particularly important in appropriate decision making on treatment for PCa (active surveillance or focal therapy or radical treatment). We aimed to compare the Gleason upgrading (GU) rates and the concordance of the Gleason scores in the biopsy versus final pathology after the surgery in patients who underwent only TRUS systematic random biopsies versus US-MRI FB for PCa. Methods: A retrospective analysis of patients’ prospective collected data that underwent prostate biopsy and subsequent radical prostatectomy were included from January 2011 to June 2016 at our institution. The study cohort was divided into: US-MRI FB (Group A) and only TRUS systematic random biopsy (Group B). US-MRI FB was performed in patients who had a previous MRI with a focal lesion classified by Likert score ≥ 3, otherwise a TRUS systematic random biopsy was performed. All biopsies and surgical specimens were analyzed by the same uropathologist and MRIs were analyzed by two expert urological radiologists. Results: 73 men underwent US-MRI FB and 89 TRUS systematic random biopsy. The GU rate was higher in group B (31.5% vs 16.4%; p = 0.027). GU according to Gleason grade pattern was higher in Group B against Group A (40.4% vs 23.3%; p = 0.02). Analyses from separate Gleason grade pattern showed that Gleason score 3+4 presented less GU in group A (24.1% vs 52.6%; p = 0.043). The Bland-Altman plot analysis showed a higher bias in Group B compared to group A (-0.27 [-1.40 to 0.86] vs -0.01 [-1.42 to 1.39]). In the multivariable logistic regression the only independent predictor of GU was the use of TRUS systematic random biopsy (2.64 [1.11 – 6.28]; p = 0.024). Conclusions: The US-MRI FB appears to be related to a decrease in GU rate and an increase in the concordance between biopsy and final pathology in comparison to TRUS random biopsy, that leads to greater accuracy on diagnosis and better treatment decision.

A model for predicting focal ablation candidates in patients with prostate cancer based on MRI and biopsy criteria.

31 Background: To determine the accuracy of multiparametric MRI (mpMRI) and fusion biopsy in predicting focal therapy candidates by correlating agreement between patients’ pre-prostatectomy MRI and biopsy findings with whole mount pathology. Methods: Patients who underwent mpMRI and biopsy followed by prostatectomy between 2010-2015 were included in the study. Patients were considered good candidates for focal therapy if they had intermediate risk cancer (max Gleason 3+4 or 4+3 on biopsy) in only one hemisphere of the prostate, and if they had an mpMRI visible lesion(s) on one hemisphere that did not cross midline. Patients were considered poor candidates for focal therapy if they had either low risk cancer (Gleason 6), high risk cancer (Gleason 8, 9 and 10), intermediate risk cancer bilaterally, MRI visible lesions that cross the midline, or contained extracapsular extension or seminal vesicle invasion. Whole mounts of patients considered good candidates were then examined histologically for maximum tumor involvement. Results: 501 patients who underwent prostatectomy between 2010 and 2015 were included in the study, with mean age 60.0 (±10.0) and PSA 6.21 (±6.0). 395 patients were considered poor focal candidates, and 106 were considered good focal candidates. Of these 106, 66 patients had whole mounts available for analysis (14 random biopsy, 52 fusion biopsy). 42/66 (63.6%) patients were confirmed as candidates (6/14 (42.9%) who had random biopsy and 36/52 (68.0%) who had fusion). Candidates failed prediction due to Gleason upgrade in final histopathology in 20/24 (83.3%), and for significant Gleason detection bilaterally in 4/24 (16.7%). Conclusions: Our results suggest that application of mpMRI and biopsy criteria to predict focal therapy candidates may result in undertreatment of a large portion of patients with significant cancer. Results from mpMRI guided targeted biopsy were shown to be a more accurate tool for predicting candidates for focal therapy than results from random biopsy alone. More accurate predictive capability is needed before focal therapy can be widely accepted.