Biopsy Gleason Grade Research Articles

Trend of Adverse Stage Migration in Patients Treated with Radical Prostatectomy for Localized Prostate Cancer

BackgroundTwo recent European studies showed an increasing proportion of non–organ-confined (NOC; pathologic stages T3–4) prostate cancer (PCa) in radical prostatectomy (RP) specimens. ObjectiveTo determine if the trend for NOC and pT3–4 PCa is also evident among contemporary North American patients. Design, setting, and participantsWithin the Surveillance, Epidemiology, and End Results database (2010–2014), we identified 58 558 patients with clinically localized PCa treated with RP. Only patients with clinical stage T1–2 and biopsy Gleason grade group (GGG) 1–3 PCa were included. Outcome measurements and statistical analysisAnnual trend analyses and multivariable logistic regression models focused on the rate of NOC PCa, the rate of primary pathologic Gleason ≥4 PCa, and the rate of either NOC PCa and/or primary pathologic Gleason ≥4 PCa. Adjustment was made for clinical tumor characteristics (prostatic specific antigen [PSA], clinical stage, and biopsy GGG). Results and limitationsThe rate of NOC PCa increased during the study period (18.7% vs 24.2%; p=0.002) and remained significant after adjustment (16.9% vs 22.3%; p=0.001) Similarly, the rate of pathologic primary Gleason ≥4 PCa increased during the study period (16.8% vs 23.0%, p=0.001) and remained significant after multivariable adjustment (10.8% vs 14.2%; p=0.002). Moreover, virtually the same findings were recorded when both endpoints were combined. Our results were confirmed in multivariable logistic regression analyses in which year of diagnosis was modeled as a continuous variable or a categorical variable or when a cubic spline approach was used. ConclusionsRates of NOC PCa and primary Gleason ≥4 PCa increased over time among contemporary North American patients treated with RP. This finding may be related to better acceptance of active surveillance and watchful waiting by North American patients. Patient summaryIn this report, we looked at pathologic outcomes for contemporary North American patients treated with radical prostatectomy. We found an increase in non–organ-confined and more aggressive prostate cancer.

Development and internal validation of a side-specific, multiparametric magnetic resonance imaging-based nomogram for the prediction of extracapsular extension of prostate cancer.

To develop a nomogram for predicting side-specific extracapsular extension (ECE) for planning nerve-sparing radical prostatectomy. We retrospectively analysed data from 561 patients who underwent robot-assisted radical prostatectomy between February 2014 and October 2015. To develop a side-specific predictive model, we considered the prostatic lobes separately. Four variables were included: prostate-specific antigen; highest ipsilateral biopsy Gleason grade; highest ipsilateral percentage core involvement; and ECE on multiparametric magnetic resonance imaging (mpMRI). A multivariable logistic regression analysis was fitted to predict side-specific ECE. A nomogram was built based on the coefficients of the logit function. Internal validation was performed using 'leave-one-out' cross-validation. Calibration was graphically investigated. The decision curve analysis was used to evaluate the net clinical benefit. The study population consisted of 829 side-specific cases, after excluding negative biopsy observations (n = 293). ECE was reported on mpMRI and final pathology in 115 (14%) and 142 (17.1%) cases, respectively. Among these, mpMRI was able to predict ECE correctly in 57 (40.1%) cases. All variables in the model except highest percentage core involvement were predictors of ECE (all P ≤ 0.006). All variables were considered for inclusion in the nomogram. After internal validation, the area under the curve was 82.11%. The model demonstrated excellent calibration and improved clinical risk prediction, especially when compared with relying on mpMRI prediction of ECE alone. When retrospectively applying the nomogram-derived probability, using a 20% threshold for performing nerve-sparing, nine out of 14 positive surgical margins (PSMs) at the site of ECE resulted above the threshold. We developed an easy-to-use model for the prediction of side-specific ECE, and hope it serves as a tool for planning nerve-sparing radical prostatectomy and in the reduction of PSM in future series.

MP46-14 LOOKING BEYOND CANCER DETECTION: IS TEMPLATE BIOPSY BETTER THAN TRUS BIOPSY IN PLANNING NERVE SPARING ROBOTIC RADICAL PROSTATECTOMY IN THE MULTIPARAMETRIC MRI ERA?

You have accessJournal of UrologyProstate Cancer: Detection & Screening IV1 Apr 2018MP46-14 LOOKING BEYOND CANCER DETECTION: IS TEMPLATE BIOPSY BETTER THAN TRUS BIOPSY IN PLANNING NERVE SPARING ROBOTIC RADICAL PROSTATECTOMY IN THE MULTIPARAMETRIC MRI ERA? Dimitrios Moschonas, Edward Bass, Pavlos Pavlakis, Murthy Kusuma, Stylianos Chintzoglou, Krishnaji Patil, Christopher Eden, Matthew Perry, and Stephen Langley Dimitrios MoschonasDimitrios Moschonas More articles by this author , Edward BassEdward Bass More articles by this author , Pavlos PavlakisPavlos Pavlakis More articles by this author , Murthy KusumaMurthy Kusuma More articles by this author , Stylianos ChintzoglouStylianos Chintzoglou More articles by this author , Krishnaji PatilKrishnaji Patil More articles by this author , Christopher EdenChristopher Eden More articles by this author , Matthew PerryMatthew Perry More articles by this author , and Stephen LangleyStephen Langley More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1473AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Surgical decision-making at radical prostatectomy is of vital importance to maximizing biochemical disease-free survival as well as quality of life. Accurate characterisation of a patient′s tumour at diagnosis is thus paramount. Whilst the bulk of existing data has focused on cancer detection, little has been done in regard to whether biopsy strategies have demonstrable effect on surgical outcome. Our aim was to assess the impact of biopsy method on nerve sparing robotic assisted radical prostatectomy (RARP) and positive surgical margin (PSM) rates. METHODS We analysed our prospectively collected data of consecutive patients who underwent primary RARP following a diagnosis of CaP at a single referral centre between October 2010 and June 2017. All patients underwent multiparametric MRI (mpMRI) and either transrectal ultrasound guided (TRUS) or template transperineal biopsy. Data included presenting PSA (pPSA); patient age; clinical and radiological T stage; biopsy type and Gleason grade; D′Amico risk classification; whole-mount Gleason grade, prostate and tumour volumes; PSM status, site and length. PSM status was compared between groups. RESULTS 771 patients were included in the study, with 343 (44.5%) having undergone TRUS and 428 (55.6%) template biopsies. Median age was 66 [IQR 60-69] and median pPSA 7.2 [IQR 5.3-10.7]. Nerve sparing procedures were performed in 273 (79.6%) men following mpMRI and TRUS and 330 (77.1%) following mpMRI and template. PSM rates were significantly higher in the mpMRI and TRUS groups than in the mpMRI and template groups (p=0.005). Subgroup analysis demonstrated advantage of mpMRI and template in D′Amico high (p=0.04) and intermediate (p=0.04) risk groups. CONCLUSIONS MpMRI and template biopsy are superior to the combination of mpMRI and TRUS in surgical planning leading to better pathologic margin outcomes for patients. Targeted biopsy strategies beyond cancer detection, confidently support clinical decision making of nerve sparing prostatectomy approach © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e611-e612 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Dimitrios Moschonas More articles by this author Edward Bass More articles by this author Pavlos Pavlakis More articles by this author Murthy Kusuma More articles by this author Stylianos Chintzoglou More articles by this author Krishnaji Patil More articles by this author Christopher Eden More articles by this author Matthew Perry More articles by this author Stephen Langley More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP40-05 EFFECTS OF INTRODUCING PRE-BIOPSY MPMRI INTO CONTEMPORARY UK PROSTATE CANCER DETECTION.

You have accessJournal of UrologyProstate Cancer: Detection & Screening III1 Apr 2018MP40-05 EFFECTS OF INTRODUCING PRE-BIOPSY MPMRI INTO CONTEMPORARY UK PROSTATE CANCER DETECTION. Catherine Hobbs, Katie Eyre, Robert McCormick, Fergus Gleeson, Ruth MacPherson, Clare Verrill, Freddie Hamdy, Simon Brewster, and Richard Bryant Catherine HobbsCatherine Hobbs More articles by this author , Katie EyreKatie Eyre More articles by this author , Robert McCormickRobert McCormick More articles by this author , Fergus GleesonFergus Gleeson More articles by this author , Ruth MacPhersonRuth MacPherson More articles by this author , Clare VerrillClare Verrill More articles by this author , Freddie HamdyFreddie Hamdy More articles by this author , Simon BrewsterSimon Brewster More articles by this author , and Richard BryantRichard Bryant More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1272AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Pre-biopsy multiparametric magnetic resonance imaging (PB-mpMRI) using the Prostate Imaging Reporting and Data System (PI-RADS) has become an adjunct to prostate cancer (PCa) diagnosis, and was incorporated into our PCa diagnostic pathway in July 2016. Interrogating our PCa series, we hypothesized that PB-mpMRI increases the diagnostic yield of transrectal prostate biopsy (TRPB), and may allow us to discontinue recommending systematic TRPB to men with a ″negative″ MRI. METHODS 997 patients underwent TRPB without PB-mpMRI in 18 months to June 2016 (cohort A), and 792 patients underwent TRPB following PB-mpMRI during the 12 months from July 2016 (cohort B), all patients being previously biopsy-naive. Patients with PB-mpMRI lesions (PI-RADS 3-5) underwent cognitive targeted plus systematic TRPB, whilst patients without targetable lesions underwent systematic TRPB. We investigated the impact of introducing PB-mpMRI on the diagnostic yield of TRPB. RESULTS Cohort B comprised younger (median 68 v 69 years, p=0.001) men with a lower PSA (median 7.6 v 7.9 ng/mL, p=0.032) and prostate volume (median 56.7 v 62 cc, p=0.006) compared with cohort A. No difference was seen in family history, finasteride use, or PSA-density (p>0.05 for each). We observed increased detection of multi-focal prostatic intraepithelial neoplasia ± atypical small acinar proliferation (p=0.018) and increased maximum PCa core length (≥5mm versus <5mm, p=0.041) in Cohort B, but no difference in overall PCa detection (57.6 v 56.7%), Gleason Grade (GG), or number of positive cores (p>0.05 for each), compared with cohort A. We also observed a significant shift towards PCa radical intervention (surgery and/or radiotherapy) for Cohort B (p<0.001). A significant correlation was observed between the PI-RADS score and overall biopsy result (R=0.612, p<0.001) and GG (R=0.569, p<0.001). 49.9% of PB-mpMRIs revealed PI-RADS 4/5 lesions (% Sensitivity, Specificity, PPV and NPV for GG Group 2-5 PCa 79.6, 78.5, 78.1 and 80.1 respectively for PI-RADs 4/5 lesions). The % sensitivity, specificity, PPV and NPV of combined PI-RADs 1/2 lesions for GG Group 2-5 PCa was 88.1, 59.8, 67.8 and 84 respectively. CONCLUSIONS 1) Introducing PB-mpMRI into our contemporary PCa detection pathway increased the diagnostic yield of TRPB by increasing the maximum cancer length per biopsy core. This may explain the observed shift towards more radical treatment interventions for PCa.2) A ″negative″ MRI scan (PI-RADS 1/2) missed GG group 2 or higher PCa detected by systematic TRPB in 16% of cases (i.e. approximately 1 in 6 cases), highlighting the need to recommend both investigations for men referred with suspected PCa. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e521 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Catherine Hobbs More articles by this author Katie Eyre More articles by this author Robert McCormick More articles by this author Fergus Gleeson More articles by this author Ruth MacPherson More articles by this author Clare Verrill More articles by this author Freddie Hamdy More articles by this author Simon Brewster More articles by this author Richard Bryant More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP16-02 ONCOLOGICAL OUTCOMES OF ROBOT-ASSISTED RADICAL PROSTATECTOMY IN ISUP GRADE 5 PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy III1 Apr 2018MP16-02 ONCOLOGICAL OUTCOMES OF ROBOT-ASSISTED RADICAL PROSTATECTOMY IN ISUP GRADE 5 PROSTATE CANCER Alexander Govorov, Konstantin Kolontarev, Pavel Rasner, Vladimir Dyakov, and Dmitry Pushkar Alexander GovorovAlexander Govorov More articles by this author , Konstantin KolontarevKonstantin Kolontarev More articles by this author , Pavel RasnerPavel Rasner More articles by this author , Vladimir DyakovVladimir Dyakov More articles by this author , and Dmitry PushkarDmitry Pushkar More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.536AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The aim of the study was to assess oncological outcomes of robot-assisted radical prostatectomy (RARP) in patients with International Society of Urological Pathology (ISUP) grade 5 prostate cancer (PCa). METHODS Prospectively collected institutional database was analyzed for different pre- and post-surgery parameters of 116 men with ISUP prostate biopsy grade 5 and clinical stage T1c-T3bN0/N1M0 PCa, who underwent RARP with bilateral pelvic lymph node dissection (PLND) from 2009 to 2016. RESULTS Median patients′ age was 62 years (IQR 55.4-67); 44.8% of men had clinically organ-confined disease, 55.2% had locally advanced PCa. After RARP 55.8% of cT2 and 46.9% of cT3 patients were upstaged to pT3-4, and 12.5% of cT3 were downstaged to pT2; 22.4% of cases were downgraded to ISUP grades 3/4. After the median follow-up of 50.2 months (IQR 28-62), 44% of patients had biochemical failure with 19.8% of PSA persistence and 24.2% biochemical recurrence (BCR). Adjuvant and salvage radiation therapy (RT) were administered to 51.7% (n=60) and 20.7% (n=24) of men respectively, from which 77.4% (n=65/84) had concomitant androgen deprivation therapy (ADT); 10.3% of men underwent only ADT and 6% - salvage PLND. Distant metastases were detected in 11.2% of patients. Death from PCa was registered in 3.4% and from other causes - in 5.2% of cases (in total 8.6%). The 5-year overall, PCa-specific, metastasis-free and disease-free survival rates were 91%, 96%, 89% and 49% respectively (with Kaplan-Meier estimate). On multivariate analysis predominant biopsy Gleason grade 5, percentage/number of positive cores with Gleason grade 5 on biopsy, pre-surgery total PSA, pathological T-stage and lymph node involvement correlated with BCR and systemic failure. Relatively short follow-up and diverse post-RARP treatment combinations are limitations of the study. CONCLUSIONS RARP in ISUP grade 5 PCa is an effective treatment option for potentially lethal form of the disease: with multimodal approach PCa-specific mortality was quite low and 49% of the patients remained disease-free. The prostate biopsy disease volume with several other parameters predicted biochemical and systemic failure, allowing identify candidates for aggressive adjuvant therapy. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e197-e198 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Alexander Govorov More articles by this author Konstantin Kolontarev More articles by this author Pavel Rasner More articles by this author Vladimir Dyakov More articles by this author Dmitry Pushkar More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Multiparametric ultrasound-targeted biopsy compares favorably to multiparametric MRI-transrectal ultrasound fusion-targeted biopsy on initial biopsy of men at risk for prostate cancer.

The purpose this study is to evaluate the efficacy of multiparametric ultrasound-targeted biopsies in patients undergoing initial biopsy of the prostate for the suspicion of prostate cancer. A total of 167 patients who are biopsy naïve underwent multiparametric ultrasound-targeted biopsy of the prostate. All patients had a transrectal ultrasound which included gray-scale evaluation and color Doppler evaluation. 12-core biopsies were performed on all patients, based on sextant anatomy; however, all cores were directed toward visually abnormal areas of the prostate as identified by multiparametric ultrasound, when such areas were present. Of 167 patients undergoing biopsy, a total of 111 (66.5%) were positive for cancer. Of these, 78 (70.3%) had a Gleason grade≥7 and 33 (29.7%) had a Gleason grade≤6. Of those undergoing radical prostatectomy 29 of 38 (76.3%) had biopsy Gleason grade≥7, while nine of 38 (23.7%) had a Gleason grade≤6. Only four of 38 (10.5%) patients who had final pathologic staging underwent surgical therapy for disease of low-malignant potential (Gleason≤6). On initial biopsy for prostate cancer, multiparametric ultrasound-targeted biopsy compares favorably to the published performance of multiparametric MRI-TRUS fusion-targeted biopsy in terms of positive biopsy rate and the detection of disease of low-malignant potential.

Lesion size on prostate magnetic resonance imaging predicts adverse radical prostatectomy pathology

Objectives: To investigate the value of the maximal lesion diameter on preoperative multiparametric/bi-parametric magnetic resonance imaging for estimating the risk of adverse radical prostatectomy pathology.Patients and methods: Consecutive patients (n = 162) with prostate multiparametric or biparametric magnetic resonance images acquired before prostatectomy were retrospectively stratified into two groups: 65 patients with normal MRI (n = 18) or a suspicious lesion <15 mm in diameter (n = 47), and 97 patients with a lesion diameter ≥15 mm. The presence of extraprostatic extension, margin positivity, seminal vesicle invasion, and lymph node metastasis was examined in these groups using logistic regression analysis, including preoperative clinical parameters (prostate-specific antigen concentration, biopsy Gleason grade group, clinical T-stage, and D’Amico risk group).Results: The prevalence of extraprostatic extension, margin positivity, and seminal vesicle invasion was 53.1% (86/162), 22.8% (37/162), and 17.9% (29/162), respectively. Lymphadenectomy was performed in 64 men, of whom 14 had lymph node metastasis. Lesion diameter ≥15 mm strongly predicted extraprostatic extension (Odds ratio: 7.94, 95% confidence interval: 3.87−16.28, p < 0.001), margin positivity (Odds ratio: 7.86, 95% confidence interval 2.63−23.51, p < 0.001), and seminal vesicle invasion (Odds ratio: 7.57, 95% confidence interval 2.18−26.22, p = 0.001). Lesion diameter ≥15 mm was an independent risk factor for adverse prostatectomy pathology. Lesion diameter ≥20 mm, but not ≥15 mm, was a significant risk factor for lymph node metastasis.Conclusion: Magnetic resonance imaging lesion diameter ≥15 mm is an independent risk factor for extraprostatic extension, margin positivity and seminal vesicle invasion.

FOXA1 expression is a strong independent predictor of early PSA recurrence in ERG negative prostate cancers treated by radical prostatectomy.

FOXA1 (Fork-head box protein A1, HNF-3a) is a transcription factor involved in androgen signaling with relevance for lineage-specific gene expression of the prostate. The expression was analyzed by immunohistochemistry on a tissue microarray containing 11152 prostate cancer specimens. Results were compared with tumor phenotype, biochemical recurrence, androgen receptor expression, ETS-related gene (ERG) status and other recurrent genomic alterations. FOXA1 expression was detectable in 97.6% of 8227 interpretable cancers and considered strong in 28.5%, moderate in 46.2% and weak in 22.9% of cases. High FOXA1 expression was associated with TMPRSS2:ERG rearrangement and ERG expression (P < 0.0001). High FOXA1 expression was linked to high Gleason grade, advanced pathological tumor (pT) stage and early PSA recurrence in ERG negative cancers (P < 0.0001), while these associations were either weak or absent in ERG positive cancers. In ERG negative cancers, the prognostic role of FOXA1 expression was independent of Gleason grade, pathological tumor stage, lymph node stage, surgical margin status and preoperative PSA. Independent prognostic value became even more evident if the analysis was limited to preoperatively available features such as biopsy Gleason grade, preoperative PSA, cT stage and FOXA1 expression (P < 0.0001). Within ERG negative cancers, FOXA1 expression was also strongly associated with PTEN and 5q21 deletions (P < 0.0001). High expression of FOXA1 is an independent prognostic parameter in ERG negative prostate cancer. Thus, FOXA1 measurement might provide clinically useful information in prostate cancer.

Changing face of robot-assisted radical prostatectomy in Melbourne over 12 years.

This study aims to characterize the trends in disease presentation for robot-assisted radical prostatectomy (RARP) over a 12-year period in Melbourne, Australia. All patients undergoing an RARP between 2004 and October 2016 while under the care of six high-volume surgeons were included in this study. Data were collected prospectively regarding patient demographics and clinical details of their cancer. Over the 12-year time span of the study, 3075 men underwent an RARP with a median age of 63.01 years. Temporal analysis demonstrated that the median age of patients undergoing prostatectomy advanced with time with the median age in 2016 being 65.51 years compared with 61.0 years in 2004 (P < 0.001). There was also a significant trend to increased D'Amico risk groups over time with the percentage procedures for high-risk patients increasing from 12.6% to 28.10% from 2004 to 2016 (P < 0.001). Upgrade rates between biopsy and pathological Gleason grade scoring significantly trended down over the period of the study (P < 0.001). There was also a shift to increased pathological stage over the 12 years with 22.1% of men having T3 disease in 2004 compared with 49.8% in 2016. Our analysis demonstrates increasing treatment of older men with higher risk tumours, consistent with international trends. While this largely reflects a shift in case selection, further work is needed to assess whether the stage shift may relate partially to a decline in screening and increased presentation of higher risk disease.

Biopsy Detected Gleason Pattern 5 is Associated with Recurrence, Metastasis and Mortality in a Cohort of Men with High Risk Prostate Cancer.

We evaluated the relative risk of biochemical recurrence, metastasis and death from prostate cancer contributed by biopsy Gleason pattern 5 among men at high risk with Gleason 8-10 disease in the SEARCH (Shared Equal Access Regional Cancer Hospital) cohort. Men with biopsy Gleason sum 8-10 prostate cancer treated with radical prostatectomy were evaluated. The cohort was divided into men with Gleason 4 + 4 vs those with any pattern 5 (ie Gleason 3 + 5, 5 + 3, 4+5, 5 + 4 or 5 + 5). Predictors of biochemical recurrence, metastases, and prostate cancer specific and overall survival were analyzed using Kaplan-Meier, log rank test and Cox proportional hazards models. We identified 634 men at high risk in the SEARCH database, of whom 394 (62%) had Gleason 4 + 4 and 240 (38%) had Gleason pattern 5 on biopsy. Baseline characteristics did not significantly differ between the groups. On multivariable analysis relative to Gleason 4 + 4 men at high risk with Gleason pattern 5 showed no difference in the risk of biochemical recurrence (HR 1.26, 95% CI 0.99-1.61, p = 0.065). However, they were at significantly greater risk for metastasis (HR 2.55, 95% CI 1.50-4.35, p = 0.001), prostate cancer specific mortality (HR 2.67, 95% CI 0.1.26-5.66, p = 0.010) and overall mortality (HR 1.60, 95% CI 1.09-2.34, p = 0.016). Preoperative subclassification of high risk prostate cancer by biopsy Gleason grade (4 + 4 vs any Gleason pattern 5) identified men at highest risk for progression. Any Gleason 5 on biopsy is associated with a greater risk of metastasis, and prostate cancer specific and overall mortality. Grouping all Gleason 8-10 tumors together as high risk lesions may fail to fully stratify men at highest risk for poor outcomes.

Salvage prostatectomy for post-radiation adenocarcinoma with treatment effect: Pathological and oncological outcomes.

Prostate biopsies following localized radiation therapy for prostate cancer often demonstrate residual prostatic carcinoma with treatment effect (CTE). The final oncological outcome of prostatic CTE is currently uncertain. We studied the pathological and oncological outcomes for a large cohort of patients who had CTE on post-radiation therapy biopsy and subsequently underwent salvage radical prostatectomy (SRP). A single-centre retrospective review of all SRPs performed from 1995-2014 was performed. Cases were selected for this analysis if they had had a post-radiation "for-cause" biopsy. Biopsy results were compared to final pathology results following SRP. Pathological and clinical outcomes were compared by extent of treatment effect seen on the post-radiation biopsy. A total of 70 patients who had salvage prostatectomy at MD Anderson Cancer Centre from 2007-2015 met study criteria. CTE was found on biopsy in the absence of other adenocarcinoma in 16 patients. Among them, one (7%) patient had no evidence of carcinoma at the time of salvage prostatectomy, four (27%) had CTE, three (20%) had adenocarcinoma with minimal or partial treatment effect (PTE), and seven (47%) had adenocarcinoma with no treatment effect (NTE). For those with CTE on biopsy, 69% had biochemical recurrence at a median time of 0.4 years (interquartile range [IQR] 0.22-1.52) vs. 52% for all patients (median 0.44 years, IQR 0.11-1.70) and 47% for those with no treatment effect (median 0.62 years, IQR 0.05-1.90). Metastasis developed after salvage prostatectomy in 11.8% of the whole cohort (8/68, median time to metastasis was 3.03 years, IQR 2.45-4.47), 26.7% of patients with CTE (median 3.2 years, IQR 1.96-4.44), and 6.7% of patients with NTE (median 2.45 years, IQR 0.98-2.86). Median recurrence-free survival was 2.78 years (95% confidence interval [CI] 0.84-5.43) for all patients, 0.51 years (95% CI 0.22-2.35) for those with CTE, and 4.95 years (95% CI 0.95-7.08) for those with NTE; the difference was not significant (p=0.13). On multivariate analysis, pre-SRP biopsy Gleason grade <7 (hazard ratio [HR] 0.38; 95% CI 0.14-1.02) and number of biopsy cores positive for carcinoma (HR 1.11; 95% CI 1.00-1.22) were significant for prediction of cancer recurrence. Patients undergoing salvage prostatectomy for CTE or PTE demonstrated in a for-cause biopsy after radiation therapy had pathological evidence of viable, untreated cancer in more than 50% of cases and were at significant risk of adverse pathological features. Patients with CTE may therefore benefit from salvage radical prostatectomy. Our study is limited by its retrospective nature and sample size. More studies are required to further validate our findings and assess the benefit of SRP in this population.

Preoperative Statin Use Associated With Lower PSA But Similar Prostate Size and Histopathologic Outcomes: Implications for Active Surveillance?

The potential effects of statins on clinical and histopathologic variables, prostate size, or PSA density (PSAD) and resulting influences on active surveillance eligibility have not been adequately explored. This study examines the effect of statins on prostate specimens following prostatectomy. Patients that received robotic-assisted laparoscopic prostatectomy (RALP) (n = 2,632) were dichotomized according to preoperative statin use. Logistic regression was used to evaluate associations between statin use and patient clinical and pathological characteristics. Men using statins at the time of prostatectomy were older (61.6 &plusmn; 6.4 versus 58.8 &plusmn; 7.2 years, P &lt; .001), and had poorer health status (P &lt; .001). Biopsy Gleason grade, clinical stage and prostate size were similar among the two groups, although statin users had lower diagnostic PSA levels (5.5 &plusmn; 3.6 versus 6.3 &plusmn; 4.9 ng/mL, P &lt; .001) and PSAD (.12 versus .13, P = .001). Men taking statins at the time of prostatectomy had similar histopathologic characteristics to non-users, despite having significantly lower serum PSA, being older and having similar sized prostates. This supports prior studies suggesting a PSA reduction effect of statins may warrant consideration of statin usage in decisionalgorithms for active surveillance.

Development and Internal Validation of a Novel Model to Identify the Candidates for Extended Pelvic Lymph Node Dissection in Prostate Cancer

BackgroundPreoperative assessment of the risk of lymph node invasion (LNI) is mandatory to identify prostate cancer (PCa) patients who should receive an extended pelvic lymph node dissection (ePLND). ObjectiveTo update a nomogram predicting LNI in contemporary PCa patients with detailed biopsy reports. Design, setting, and participantsOverall, 681 patients with detailed biopsy information, evaluated by a high-volume uropathologist, treated with radical prostatectomy and ePLND between 2011 and 2016 were identified. Outcome measurements and statistical analysisA multivariable logistic regression model predicting LNI was fitted and represented the basis for a coefficient-based nomogram. The model was evaluated using the receiver operating characteristic-derived area under the curve (AUC), calibration plot, and decision-curve analyses (DCAs). Results and limitationsThe median number of nodes removed was 16. Overall, 79 (12%) patients had LNI. A multivariable model that included prostate-specific antigen, clinical stage, biopsy Gleason grade group, percentage of cores with highest-grade PCa, and percentage of cores with lower-grade disease represented the basis for the nomogram. After cross validation, the predictive accuracy of these predictors in our cohort was 90.8% and the DCA demonstrated improved risk prediction against threshold probabilities of LNI ≤20%. Using a cutoff of 7%, 471 (69%) ePLNDs would be spared and LNI would be missed in seven (1.5%) patients. As compared with the Briganti and Memorial Sloan Kettering Cancer Center nomograms, the novel model showed higher AUC (90.8% vs 89.5% vs 89.5%), better calibration characteristics, and a higher net benefit at DCA. ConclusionsAn ePLND should be avoided in patients with detailed biopsy information and a risk of nodal involvement below 7%, in order to spare approximately 70% ePLNDs at the cost of missing only 1.5% LNIs. Patient summaryWe developed a novel nomogram to predict lymph node invasion (LNI) in patients with clinically localized prostate cancer based on detailed biopsy reports. A lymph node dissection exclusively in men with a risk of LNI >7% according to this model would significantly reduce the number of unnecessary pelvic nodal dissections with a risk of missing only 1.5% of patients with LNI.

High concordance of findings obtained from transgluteal magnetic resonance imaging - and transrectal ultrasonography-guided biopsy as compared with prostatectomy specimens.

To determine the utility of our transgluteal magnetic resonance imaging (MRI)-guided prostate biopsy approach. A total of 960 biopsy series, taken within the period of 1 year, were evaluated, including 301 MRI-guided and 659 transrectal ultrasonography (TRUS)-guided biopsies. The positivity rate and proportion of high grade cancers were significantly higher in MRI-guided than in TRUS-guided biopsies. Of 301 MRI-guided biopsies, 65.4% contained cancer while 57.2% of 659 TRUS biopsies contained cancer (P = 0.016). Gleason grade 3 + 3 = 6 disease was observed in 16.8% of 197 MRI-guided and in 36.1% of 377 TRUS-guided biopsies (P < 0.001). There was also a markedly higher quantity of cancer tissue in MRI-guided biopsies. In all cancers, the mean cancer surface area was 64.8 ± 51.6 mm2 in MRI-guided biopsies as compared with 23.0 ± 31.4 mm2 in non-MRI-guided biopsies (P < 0.001). With respect to the tissue quantity, superiority of MRI-guided biopsy was highest in Gleason grade 3 + 3 = 6 cancers (20.9 ± 27.9 vs 5.1 ± 10.2 mm2 ; P < 0.001) and in Gleason grade 3 + 4 = 7 cancers (59.7 ± 38.0 vs 17.7 ± 18.4 mm2 ; P < 0.001). Comparison of biopsy Gleason grades with findings in prostatectomy specimens was possible in 80 patients with MRI-guided and in 170 patients with non-MRI-guided biopsies. This comparison showed a very high but almost identical concordance of TRUS- and MRI-guided biopsies with the prostatectomy specimen findings. With both approaches, undetected high-risk cancers were present in ~10% of patients with low-risk biopsy results. A significant difference was observed, however, in the proportion of patients who had clinically insignificant cancers and who underwent surgery. The proportion of patients with Gleason grade 3 + 3 = 6 carcinoma in their prostatectomy specimen was 11.2% in the post-TRUS biopsy cohort, but only 2.5% in the post-MRI biopsy cohort (P = 0.021). MRI-guided transgluteal prostate biopsy has a high detection rate for high-risk carcinomas, while the risk of detecting clinically insignificant carcinomas appears to be reduced. This may by itself lead to a reduction of unnecessary prostatectomies. Overtreatment may be further avoided by better applicability of molecular testing to MRI-guided biopsies because of the excessive amount of tissue available for analysis, especially in patients with potential low-risk carcinomas.

MP14-02 THE NATURAL HISTORY OF MEN ON ACTIVE SURVEILLANCE WITH LOW-RISK PROSTATE CANCER AT A SAFETY-NET, COUNTY HOSPITAL

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History II1 Apr 2017MP14-02 THE NATURAL HISTORY OF MEN ON ACTIVE SURVEILLANCE WITH LOW-RISK PROSTATE CANCER AT A SAFETY-NET, COUNTY HOSPITAL E. Charles Osterberg, Nynikka Palmer, Catherine Harris, Gregory Murphy, Sarah Blaschko, Carissa Chu, Matthew Cooperberg, Peter Carroll, and Benjamin Breyer E. Charles OsterbergE. Charles Osterberg More articles by this author , Nynikka PalmerNynikka Palmer More articles by this author , Catherine HarrisCatherine Harris More articles by this author , Gregory MurphyGregory Murphy More articles by this author , Sarah BlaschkoSarah Blaschko More articles by this author , Carissa ChuCarissa Chu More articles by this author , Matthew CooperbergMatthew Cooperberg More articles by this author , Peter CarrollPeter Carroll More articles by this author , and Benjamin BreyerBenjamin Breyer More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.466AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Health care delivery to vulnerable and uninsured patients is challenging due to social and economic barriers. For men with low-risk prostate cancer (PCa) on active surveillance (AS), patient compliance, follow up, and access to care are essential for favorable cancer outcomes. Our primary objective is to characterize demographic, disease and cancer outcomes of men on AS at a safety-net hospital and characterize those who were loss to follow-up (LTFU). METHODS From January 2004 to November 2014, 104 men at Zuckerberg San Francisco General (ZSFG) with low-risk PCa were followed with AS. Criteria for AS has evolved over time; however, patients with diagnostic PSA 10ng/mL or less, clinical stage T1/2, biopsy Gleason grade 3+3 or 3+4, 33% or fewer positive cores and 50% or less tumor in any single core were eligible for AS. Men were longitudinally followed with a PSA and/or DRE every 3-6 months and repeat prostate biopsy every 1-2 years. Clinical staging and grading were based on a physical exam and at least a 12-core biopsy respectively. LTFU was defined as failure to contact patients with three phone calls or any urology visit recorded within 18 months from a prior visit or biopsy. A secondary chart review was performed with EPIC Systems© CareEverywhere which allows access to non-ZSFG institutions to confirm patients were truly LTFU. RESULTS Among the 104 men on AS at ZSFG, the median age at diagnosis of PCa was 61.5 years (range: 44-81). The median follow-up time period was 29 months (0-186 months) during which 18 men were LTFU and 48 remained on surveillance. Men who remained on AS underwent a median of 7 (1-21) serum PSA measurements and an average of 2 prostate biopsies (1-5). In total, 22 (20.6%) men had definitive treatment with the median time from diagnosis to active treatment being 26 (2-87) months. Radiation therapy was more common that radical prostatectomy (12.5% versus 7.7%). There was one prostate cancer-related death and three non-cancer deaths. Kaplan-Meir curve analysis demonstrates that initial adherence to AS is poor; however as time progresses, adherence increases as those patients committed to early surveillance continue with follow-up. CONCLUSIONS AS for low-risk prostate cancer is challenging among a vulnerable population receiving care in a safety-net hospital, as rates of LTFU were high. Our findings suggest the need for an AS program to improve adherence and follow-up among vulnerable and underserved populations. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e162-e163 Advertisement Copyright & Permissions© 2017MetricsAuthor Information E. Charles Osterberg More articles by this author Nynikka Palmer More articles by this author Catherine Harris More articles by this author Gregory Murphy More articles by this author Sarah Blaschko More articles by this author Carissa Chu More articles by this author Matthew Cooperberg More articles by this author Peter Carroll More articles by this author Benjamin Breyer More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

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.

Establishment and evaluation of nomogram for predicting biochemical recurrence in patients with locally adverse pathologic features after radical prostatectomy

Objective To construct and evaluate a nomogram for predicting biochemical recurrence (BCR) in patients with locally adverse pathologic features (including seminal vesicle invasion (SVI), extracapsular extension (ECE), or positive surgical margins (PSM)) after radical prostatectomy. Methods This study included prostate cancer patients who were treated with radical prostatectomy (RP) at a single institution between 2003 and 2014, with locally adverse pathological features. The final study comprised of 172 men (median age, 70 years) with a median serum PSA level of 16.1 ng/ml. According to the modified Gleason grade system, the distribution of biopsy Gleason score was as follows: Gleason≤6 (59, 34.3%), Gleason 3+ 4 (51, 29.7%), Gleason 4+ 3 (42, 24.4%), Gleason 8 (18, 10.5%), and Gleason 9-10 (2, 1.2%). Most patients were preoperatively under-staged, with 91.3% of cases had a clinical stage less than T2c. Pathological examination of the species revealed ECE in 108 (62.8%) patients, SVI in 40 (23.3%) patients and PSM in 62 (36.0%) patients. Considering the modified Gleason grading system, the distribution of the patients was as follows: Gleason≤6 (35, 20.3%), Gleason 3+ 4 (54, 31.4%), Gleason 4+ 3 (42, 24.4%), Gleason 8 (23, 13.4%), and Gleason 9-10 (18, 10.5%). Overall, there were 79.1% of patients had early postoperative PSA <0.1 ng/ml. Univariate and multivariate Cox regression analysis the value of factors in predicting the probability of BCR. Variables significantly associated with BCR were included to construct the nomogram. Concordance index and calibration curve were used for the internal validation of nomogram. Results The overall 3-year and 5-year BCR-free survival rate was 60.4% and 43.2% respectively for the entire cohort. In univariate Cox regression analysis, Preoperative PSA(HR=1.474, P<0.05), Early postoperative PSA(HR=3.488, P<0.05), SVI(HR=3.488, P<0.05), PSM(HR=1.795, P<0.05), biopsy Gleason grade(HR=1.795, P<0.05) and specimen Gleason grade(HR=1.898, P<0.05) were significantly associated with BCR. However, in multivariate analysis, only specimen Gleason grade(HR=1.809, P<0.05) and early postoperative PSA(HR=2.490, P<0.05) retained independent significance. The nomogram predicting the risk of BCR showed relative good concordance index (0.766) and good calibration. Conclusions The nomogram to predict the probability of BCR in patients with locally adverse pathologic features after radical prostatectomy showed good clinical applicability. This statistical tool may facilitate discussions at the point of treatment decision making. Key words: Prostatic neoplasms; Radical prostatectomy; Biochemical recurrence; Risk factors; Nomogram

Predictive models and risk of biopsy progression in active surveillance patients

ObjectiveTo analyze the performance of different radical prostatectomy–based prognostic tools in predicting the biopsy progression in our active surveillance cohort. Materials and methodsWe analyzed 326 patients with biopsy Gleason grade≤6,≤2 positive biopsy cores,≤20% tumor present in any core, prostate-specific antigen<15ng/dl, and clinical stages T1–T2a all of whom had at least single surveillance biopsy. Probabilities of pathologically relatively aggressive disease were estimated using Partin and Dinh risk tables and Kattan, Truong, and Kulkarni nomograms for each individual patient. Using these predictions, performance of these tools was quantified regarding discrimination, stratification at different cut-points, calibration, and the clinical net benefit. ResultsPredictions of Partin and Dinh tables were not associated with the biopsy progression. The predictive value of Kattan and Truong nomograms was higher when compared with the other tools, although it was significant only on the first and second surveillance biopsies. Both nomograms were able to identify low- and high-risk subgroups within the cohort. Kattan nomogram demonstrated better correlation with the observed rate of progression over the first 3 biopsies and higher clinical net benefit. ConclusionKattan and Truong nomograms demonstrated the best performance in predicting biopsy progression, although their value was largely limited to the first 2 surveillance biopsies. Both tools were able to stratify patients into subgroups with different risks of progression. These nomograms have important differences, which suggest that a more effective predictive model combining the strong sides of both tools and possibly some other variables could be developed.

Improving Clinical Risk Stratification at Diagnosis in Primary Prostate Cancer: A Prognostic Modelling Study.

IntroductionOver 80% of the nearly 1 million men diagnosed with prostate cancer annually worldwide present with localised or locally advanced non-metastatic disease. Risk stratification is the cornerstone for clinical decision making and treatment selection for these men. The most widely applied stratification systems use presenting prostate-specific antigen (PSA) concentration, biopsy Gleason grade, and clinical stage to classify patients as low, intermediate, or high risk. There is, however, significant heterogeneity in outcomes within these standard groupings. The International Society of Urological Pathology (ISUP) has recently adopted a prognosis-based pathological classification that has yet to be included within a risk stratification system. Here we developed and tested a new stratification system based on the number of individual risk factors and incorporating the new ISUP prognostic score.Methods and FindingsDiagnostic clinicopathological data from 10,139 men with non-metastatic prostate cancer were available for this study from the Public Health England National Cancer Registration Service Eastern Office. This cohort was divided into a training set (n = 6,026; 1,557 total deaths, with 462 from prostate cancer) and a testing set (n = 4,113; 1,053 total deaths, with 327 from prostate cancer). The median follow-up was 6.9 y, and the primary outcome measure was prostate-cancer-specific mortality (PCSM). An external validation cohort (n = 1,706) was also used. Patients were first categorised as low, intermediate, or high risk using the current three-stratum stratification system endorsed by the National Institute for Health and Care Excellence (NICE) guidelines. The variables used to define the groups (PSA concentration, Gleason grading, and clinical stage) were then used to sub-stratify within each risk category by testing the individual and then combined number of risk factors. In addition, we incorporated the new ISUP prognostic score as a discriminator. Using this approach, a new five-stratum risk stratification system was produced, and its prognostic power was compared against the current system, with PCSM as the outcome. The results were analysed using a Cox hazards model, the log-rank test, Kaplan-Meier curves, competing-risks regression, and concordance indices. In the training set, the new risk stratification system identified distinct subgroups with different risks of PCSM in pair-wise comparison (p < 0.0001). Specifically, the new classification identified a very low-risk group (Group 1), a subgroup of intermediate-risk cancers with a low PCSM risk (Group 2, hazard ratio [HR] 1.62 [95% CI 0.96–2.75]), and a subgroup of intermediate-risk cancers with an increased PCSM risk (Group 3, HR 3.35 [95% CI 2.04–5.49]) (p < 0.0001). High-risk cancers were also sub-classified by the new system into subgroups with lower and higher PCSM risk: Group 4 (HR 5.03 [95% CI 3.25–7.80]) and Group 5 (HR 17.28 [95% CI 11.2–26.67]) (p < 0.0001), respectively. These results were recapitulated in the testing set and remained robust after inclusion of competing risks. In comparison to the current risk stratification system, the new system demonstrated improved prognostic performance, with a concordance index of 0.75 (95% CI 0.72–0.77) versus 0.69 (95% CI 0.66–0.71) (p < 0.0001). In an external cohort, the new system achieved a concordance index of 0.79 (95% CI 0.75–0.84) for predicting PCSM versus 0.66 (95% CI 0.63–0.69) (p < 0.0001) for the current NICE risk stratification system. The main limitations of the study were that it was registry based and that follow-up was relatively short.ConclusionsA novel and simple five-stratum risk stratification system outperforms the standard three-stratum risk stratification system in predicting the risk of PCSM at diagnosis in men with primary non-metastatic prostate cancer, even when accounting for competing risks. This model also allows delineation of new clinically relevant subgroups of men who might potentially receive more appropriate therapy for their disease. Future research will seek to validate our results in external datasets and will explore the value of including additional variables in the system in order in improve prognostic performance.

Serial Anatomical Prostate Ultrasound during Prostate Cancer Active Surveillance

The growth potential of low grade prostate cancer is unknown and yet it is potentially impactful for the practice of active surveillance. We evaluated the incidence, growth dynamics and clinical significance of changes in prostate lesions on serial transrectal ultrasound among a large cohort of men with prostate cancer managed by active surveillance. This retrospective study included men with prostate cancer treated with active surveillance at UCSF (University of California-SanFrancisco) from 2000 to 2014 who underwent a minimum of 2 transrectal ultrasound studies. Study inclusion criteria were prostate specific antigen 20ng/ml or less, clinical stage T2 or less and biopsy Gleason grade 3 + 4 or less. Progression end points included an increase in imaging stage, a 50% or greater increase in volume and an increase in the number of sites (sextants) with apparent lesions. The relationship between transrectal ultrasound progression and biopsy Gleason upgrade was assessed by univariate and multivariate logistic regression models. The 875 identified patients underwent a median of 5 transrectal ultrasound studies (IQR 3-8). Median followup was 49 months (IQR 27-81). Ofthe patients 345 (39%) progressed on serial transrectal ultrasound, including 51 by size, 265 by the number of lesion sites and 279 by stage. Median time to progression was 14 months. Transrectal ultrasound progression was independently associated with biopsy upgrade (OR 1.8, 95% CI 1.3-2.5, p <0.01). Local progression on transrectal ultrasound was associated with Gleason upgrade at biopsy. These results suggest that stable imaging findings on transrectal ultrasound may allow for increased intervals between biopsies among men on active surveillance. A prospective study is required to evaluate the usefulness of such a practice.