Detection of Clinically Significant Index Prostate Cancer Using Micro-ultrasound: Correlation With Radical Prostatectomy.

OBJECTIVE: To determine the detection of clinically significant prostate cancer (csPCa) index lesion using high resolution transrectal micro-ultrasound (MicroUS) applying PRI-MUS (Prostate Risk Identification using Micro Ultrasound) score v1.0. METHODS: Men who underwent radical prostatectomy following biopsy and MicroUS assessment were included. MicroUS dynamic cine loops of these patients were retrospectively reviewed by an experienced radiologist. The radiologist was aware that patients had undergone radical prostatectomy but was blinded to pathological data. Suspicious sites were assigned a PRI-MUS score. Radical prostatectomy specimens were examined with the quarter mount technique. Detection rate of csPCa index lesion [Grade Group (GG) ≥2] by MicroUS was assessed at a patient level. RESULTS: Twenty-five participants were included in the analysis. The median age was 65.5 years (range 56-74). Median PSA was 6.45 ng/dL (range 2-31.72). Two of 25 patients did not have csPCa (GG1 disease) on radical prostatectomy. MicroUS visualized 20/23 (87%) of the csPCa index lesions [median length 9 mm (range 1.5- 28.5)]. All identified lesions were categorized PRIMUS score 4 or 5. The 3 missed index lesions were in the transition zone [median length 10.5 mm (range 4.5-22.5)]. MicroUS missed 11 non index csPCa in 9 participants [median length 1.5 mm (range 1.5-10.5)]. Of these, 8 were GG2, 2 GG3 and 1 GG5. MicroUS identified the csPCa index lesion in all 9 of these men. CONCLUSION: MicroUS showed the high sensitivity (87%) in detecting index lesions in the prostate gland and identified 100% of index lesions in the peripheral zone.

Preclinical studies show using enzalutamide is less effective in docetaxel-pretreated than in docetaxel-naïve prostate cancer cells.

Anti-androgen therapy with Enzalutamide (Enz) has been used as a therapy for castration resistant prostate cancer (CRPC) patients after development of resistance to chemotherapy with Docetaxel (Doc). The potential impacts of Doc-chemotherapy on the subsequent Enz treatment, however, remain unclear. Here we found the overall survival rate of patients that received Enz was significantly less in patients that received prior Doc-chemotherapy than those who had not. In vitro studies from 3 established Doc resistant CRPC (DocRPC) cell lines are consistent with the clinical findings showing DocRPC patients had decreased Enz-sensitivity as well as accelerated development of Enz-resistance via enhanced androgen receptor (AR) splicing variant 7 (ARv7) expression. Mechanism dissection found that Doc treatment might increase the generation of ARv7 via altering the MALAT1-SF2 RNA splicing complex. Preclinical studies using in vivo mouse models and in vitro cell lines proved that targeting the MALAT1/SF2/ARv7 axis with small molecules, including siMALAT1, shSF2, and shARv7 or ARv7 degradation enhancers: Cisplatin or ASC-J9®, can restore/increase the Enz sensitivity to further suppress DocRPC cell growth. Therefore, combined therapy of Doc-chemotherapy with anti-ARv7 therapy, including Cisplatin or ASC-J9®, may be developed to increase the efficacy of Enz to further suppress DocRPC in patients.

Variation in Adequate Lymph Node Yield for Gastric, Lung, and Bladder Cancer: Attributable to the Surgeon, Pathologist, or Hospital?

BACKGROUND: The Commission on Cancer recently released quality-of-care measures regarding adequate lymphadenectomy for colon, gastric, lung, and bladder cancer. There is currently little information regarding variation in adequate lymph node yield (ALNY) for gastric, lung, and bladder cancer. METHODS: The New York State Cancer Registry and Statewide Planning and Research Cooperative System were queried for stage I-III gastric, stage I-II lung, and stage II-III bladder cancer resections from 2004 to 2014. Hierarchical models assessed factors associated with ALNY (gastric ≥ 15; lung ≥ 10; bladder ≥ 2). Additionally, the proportions of variation attributable to surgeons, pathologists, and hospitals were estimated among Medicare patients. RESULTS: Among 3716 gastric, 18,328 lung, and 1512 bladder cancer resections, there were low rates of ALNY (gastric = 53%, lung = 36%, bladder = 67%). When comparing 2004-2006 and 2012-2014, there was significant improvement in ALNY for gastric cancer (39% vs. 68%), but more modest improvement for lung (33% vs. 38%) and bladder (65% vs. 71%) cancer. Large provider-level variation existed for each organ system. After controlling for patient-level factors/variation, the majority of variation was attributable to hospitals (gastric: surgeon = 4%, pathologist = 2.8%, hospital = 40%; lung: surgeon = 13.8%, pathologist = 1.5%, hospital = 18.3%) for gastric and lung cancer. For bladder cancer, most of the variation was attributable to pathologists (surgeon = 3.3%, pathologist = 10.5%, hospital = 6.2%). CONCLUSIONS: ALNY rates are low for gastric, lung, and bladder cancer, with only modest improvement over time for lung and bladder cancer. Given that the proportion of variation attributable to the surgeon, pathologist, and hospital is different for each organ system, future quality improvement initiatives should target the underlying causes, which vary by individual organ system.

Cribriform pattern and perineural invasion on MR/US fusion biopsy predict failure of selection criteria for prostatic hemigland ablation.

OBJECTIVES: To assess clinicopathologic factors on MR/US fusion biopsy that might predict failure of theoretical selection criteria for prostatic hemigland ablation (HA). SUBJECTS AND METHODS: A retrospectively maintained single institution multiparametric MRI database (n = 1667) was queried to identify 355 patients who underwent MR/US fusion biopsy, including both targeted biopsy and concurrent systematic biopsy from December 1, 2014 to June 1, 2018. Clinical, pathological, and imaging variables were assessed on fusion biopsy (Table 1) to determine who met theoretical selection criteria for HA, defined as unilateral intermediate-risk prostate cancer per NCCN criteria (Grade Group [GG] 2 or 3 with prostate-specific antigen <20) and no evidence of extraprostatic extension (EPE) on multiparametric MRI. Predictors of selection criteria failure were then assessed in patients who also underwent radical prostatectomy (RP). Failure of the theoretical HA selection criteria was defined as presence of GG ≧ 2 on the contralateral (untreated) side, or the presence of high-risk disease (any GG ≧ 4 or EPE) in the RP specimen. RESULTS: Of the 355 patients who underwent fusion biopsy, 84 patients met the theoretical selection criteria for HA. Of those patients eligible, 54 underwent RP, 37 (68.5%) of which represented unsuccessful HA selection criteria. Patients no longer met HA selection criteria on the basis of upgrading alone in 6/54 (11.1%), EPE alone in 9/54 (16.7%), bilateral GG 2 or 3 in 16/54 (29.6%) or combined EPE and bilateral GG 2 or 3 in 6/54 (11.1%) cases. In the HA selection failures due to upgrading, three also had EPE, one of whom also had missed contralateral GG ≧ 2 disease. The only factor independently associated with HA failure was any presence of cribriform pattern (HR 7.01, P = 0.021). Perineural invasion on systematic biopsyalso appeared to improve the performance of our multivariable model (HR 5.33, P = 0.052), though it was not statistically significant when using a cutoff of <0.05. Accuracy for predicting successful HA was 0.32 and improved to 0.74 if PNI or cribriform were excluded and 0.84 if both were excluded. CONCLUSIONS: In a retrospective analysis of RP patients who underwent preoperative MRI/US fusion biopsy, current selection criteria for prostatic HA based on NCCN intermediate-risk stratification failed to accurately identify appropriate candidates in 68.5% of patients. Cribriform pattern and PNI detected on biopsy reduced the failure of hemigland selection criteria to 43%. These criteria should be routinely reported on biopsy pathology and taken into consideration when selecting patients for HA in prospective clinical trials.

Multi-institutional Clinical Tool for Predicting High-risk Lesions on 3Tesla Multiparametric Prostate Magnetic Resonance Imaging.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) for prostate cancer detection without careful patient selection may lead to excessive resource utilization and costs. OBJECTIVE: To develop and validate a clinical tool for predicting the presence of high-risk lesions on mpMRI. DESIGN, SETTING, AND PARTICIPANTS: Four tertiary care centers were included in this retrospective and prospective study (BiRCH Study Collaborative). Statistical models were generated using 1269 biopsy-naive, prior negative biopsy, and active surveillance patients who underwent mpMRI. Using age, prostate-specific antigen, and prostate volume, a support vector machine model was developed for predicting the probability of harboring Prostate Imaging Reporting and Data System 4 or 5 lesions. The accuracy of future predictions was then prospectively assessed in 214 consecutive patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Receiver operating characteristic, calibration, and decision curves were generated to assess model performance. RESULTS AND LIMITATIONS: For biopsy-naïve and prior negative biopsy patients (n=811), the area under the curve (AUC) was 0.730 on internal validation. Excellent calibration and high net clinical benefit were observed. On prospective external validation at two separate institutions (n=88 and n=126), the machine learning model discriminated with AUCs of 0.740 and 0.744, respectively. The final model was developed on the Microsoft Azure Machine Learning platform (birch.azurewebsites.net). This model requires a prostate volume measurement as input. CONCLUSIONS: In patients who are naïve to biopsy or those with a prior negative biopsy, BiRCH models can be used to select patients for mpMRI. PATIENT SUMMARY: In this multicenter study, we developed and prospectively validated a calculator that can be used to predict prostate magnetic resonance imaging (MRI) results using patient age, prostate-specific antigen, and prostate volume as input. This tool can aid health care professionals and patients to make an informed decision regarding whether to get an MRI.

Predicting Benign Prostate Pathology on Magnetic Resonance Imaging/Ultrasound Fusion Biopsy in Men with a Prior Negative 12-core Systematic Biopsy: External Validation of a Prognostic Nomogram.

BACKGROUND: Magnetic resonance imaging (MRI) of the prostate after a prior negative biopsy may reduce the need for unnecessary repeat biopsies. OBJECTIVE: To externally validate a previously developed nomogram predicting benign prostate pathology on MRI/ultrasound (US) fusion-targeted biopsy in men with a Prostate Imaging Reporting and Data System (PI-RADS) 3-5 region of interest and a prior negative 12-core systematic biopsy, and update this nomogram to improve its performance. DESIGN, SETTING, AND PARTICIPANTS: A total of 2063 men underwent MRI/US fusion-targeted biopsy from April 2012 to September 2017; 104 men with a negative systematic biopsy followed by MRI-US fusion-targeted biopsy of a PI-RADS 3-5 region of interest (58%) met the study inclusion criteria. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: An MRI-based nomogram that had previously been developed in a multi-institutional clinical setting was externally validated. Predictive characteristics were age, prostate volume, MRI PI-RADS score, and prostate-specific antigen (PSA). Bayesian logistic regression was used to update the previous model. RESULTS AND LIMITATIONS: Median age of the external validation cohort was 68 yr, PSA was 7.2ng/ml, and biopsy confirmed benign pathology in 30% (n=31), suggesting a lower baseline risk compared with the nomogram development cohort. Receiver operating characteristic curve analysis showed areas under curve (AUCs) from 0.77 to 0.80 for nomogram validation. An updated model was constructed with improved calibration and similar discrimination (AUC 0.79). CONCLUSIONS: Age, prostate volume, PI-RADS, and PSA predict benign pathology on MRI/US fusion-targeted biopsy in men with a prior negative 12-core systematic biopsy. The validated and updated nomogram demonstrated high diagnostic accuracy and may further aid in the decision to avoid a biopsy in men with a prior negative biopsy. PATIENT SUMMARY: We externally validated a clinically useful tool that predicts benign prostate pathology on magnetic resonance imaging/ultrasound fusion-targeted biopsy in men with a prior negative 12-core systematic biopsy and updated this predictive tool to improve its performance in patient counseling regarding the need for a repeat biopsy.

Historical and contemporary perspectives on cribriform morphology in prostate cancer.

The Gleason scoring system is widely used for the grading and prognostication of prostate cancer. A Gleason pattern 4 subtype known as cribriform morphology has now been recognized as an aggressive and often lethal pattern of prostate cancer. The vast majority of published and ongoing prostate cancer studies still do not acknowledge the prognostic differences between various Gleason pattern 4 morphologies. As a result, current treatment recommendations are likely to be imprecise and not tailored towards patients who are most likely to die from the disease. Use of active surveillance for patients with Gleason score 3 + 4 prostate cancer has been suggested. However, the success of such paradigms would require cribriform morphology to be reported at the time of prostate biopsy, as patients harbouring such a pattern are poor candidates for surveillance. To date, only a limited number of studies have described the molecular alterations that occur in the cribriform morphological pattern. Further refinement of prostate cancer grading paradigms to distinguish cribriform from noncribriform Gleason pattern 4 is essential.

Multi-institutional nomogram predicting benign prostate pathology on magnetic resonance/ultrasound fusion biopsy in men with a prior negative 12-core systematic biopsy.

BACKGROUND: Prostate multiparametric magnetic resonance imaging (mpMRI) may be recommended for patients with a prior negative systematic biopsy (SB). However, a proportion of these patients will continue to have no prostate cancer (PCa) identified on magnetic resonance/ultrasound fusion biopsy (FB) despite abnormal mpMRI findings. METHODS: In this multi-institutional, retrospective study, clinical and mpMRI parameters were assessed for 285 consecutive patients with at least 1 prior negative biopsy who underwent FB for a Prostate Imaging Reporting and Data System (PI-RADS) score of 3 to 5 at the University of Rochester Medical Center from December 2014 to December 2016, or at the University of Alabama at Birmingham from February 2014 to February 2017. Nomograms were generated for predicting benign prostate pathology on both the targeted biopsy and the concurrent SB. RESULTS: Benign pathology was found in 132 of 285 patients (46.3%). In a multivariate analysis, the predictors of benign prostate pathology on FB were age, prostate-specific antigen, prostate volume, and PI-RADS score. The predicted probabilities were plotted on a receiver operating characteristic curve, and the area under the curve was 0.825. The nomogram demonstrated excellent calibration and a high net benefit in a decision curve analysis. With a theoretical cutoff probability of ≥0.7 used to recommend deferment of FB, 61 of 285 patients (21.4%) would have avoided an unnecessary biopsy, and only 4 of 285 patients (1.4%) with PCa with a Gleason score ≥ 3 + 4 would have been missed. CONCLUSIONS: False-positive mpMRI examinations may occur in up to 46.3% of patients with a prior negative biopsy. Thus, a multi-institutional nomogram has been developed and validated for predicting benign pathology after FB in patients with a prior negative biopsy, and this may help to reduce the number of unnecessary biopsies in the setting of abnormal mpMRI findings. Cancer 2018;124:278-85. © 2017 American Cancer Society.

A Comprehensive Analysis of Cribriform Morphology on Magnetic Resonance Imaging/Ultrasound Fusion Biopsy Correlated with Radical Prostatectomy Specimens.

PURPOSE: Recently a large body of evidence has emerged indicating that cribriform morphology is an aggressive prostate cancer morphological pattern associated with higher cancer specific mortality. In a comprehensive analysis we compared traditional and contemporary prostate biopsy techniques to detect prostate cancer with cribriform morphology with radical prostatectomy serving as the reference standard. MATERIALS AND METHODS: We queried a retrospectively maintained, single institution, multiparametric magnetic resonance imaging database of 1,001 patients to identify 240 who underwent magnetic resonance imaging-ultrasound fusion targeted biopsy and concurrent systematic biopsy from December 2014 to December 2016. Of the 3,978 biopsy cores obtained 694 positive cores were rereviewed by a genitourinary pathologist for pattern 4 subtype (cribriform, fused and poorly formed glands). Using paired analysis pathological results among 3 biopsy methods (systematic biopsy, targeted biopsy and systematic plus targeted biopsy) were compared. Prostatectomy specimens were also pathologically reviewed. RESULTS: Systematic plus targeted biopsy was superior to systematic biopsy alone or targeted biopsy alone to detect cribriform morphology (all p <0.0001). On final histopathology cribriform tumor foci were associated with an increased percent of pattern 4 involvement and extraprostatic extension (p <0.0001 and 0.003, respectively). Only 17.4% of cribriform tumors in pure form were visible on multiparametric magnetic resonance imaging. Based on final histopathology the sensitivity of systematic biopsy, targeted biopsy and systematic plus targeted biopsy for cribriform morphology was 20.7%, 28.6% and 37.1%, respectively. CONCLUSIONS: Although systematic plus targeted biopsy was the most accurate biopsy method to detect cribriform morphology, biopsy sensitivity and specificity remained poor.

Institutional Learning Curve Associated with Implementation of a Magnetic Resonance/Transrectal Ultrasound Fusion Biopsy Program Using PI-RADS™ Version 2: Factors that Influence Success.

INTRODUCTION: We assessed the institutional learning curve associated with adopting fusion biopsy using PI-RADS™ (Prostate Imaging-Reporting and Data System) Version 2 (v2) to detect clinically significant prostate cancer, defined as Gleason 7 or greater in men with prior negative biopsies, and identified patient and technical factors that predict success in detecting clinically significant prostate cancer. METHODS: A total of 113 consecutive patients with at least 1 prior negative biopsy and multiparametric magnetic resonance imaging examination of the prostate with a PI-RADS 3 or greater index lesion underwent fusion biopsy at a single academic center previously naïve to fusion biopsy technology. Outcomes include detection rates for Gleason 6 cancer, clinically significant prostate cancer and any cancer. Multiple logistic regression with model selection was used to select covariates having significant effects on the outcome. RESULTS: Prostate cancer was identified in 52% of patients with prior negative prostate biopsies. Among the patients diagnosed with prostate cancer 80% had clinically significant cancer. The clinically significant prostate cancer detection rates using fusion biopsy when a PI-RADS 3, 4 or 5 index lesion was present on multiparametric magnetic resonance imaging were 6%, 46% and 66%, respectively. PI-RADS v2 score had a predictive accuracy (AUC) of 0.79 for clinically significant prostate cancer detection. Institutional experience over time, magnetic resonance imaging estimated prostate volume and PI-RADS v2 score were independent predictors of clinically significant prostate cancer using fusion biopsy. CONCLUSIONS: Since fusion biopsy is a highly technique driven process, development of internal quality measures to assess the institutional learning curve and the quality of PI-RADS v2 scoring is critical with the adoption of this technology.

Perineural invasion by prostate cancer on MR/US fusion targeted biopsy is associated with extraprostatic extension and early biochemical recurrence after radical prostatectomy.

In recent years, multiparametric magnetic resonance imaging and magnetic resonance/ultrasound fusion targeted biopsy (TB) have become more widely adopted to aid in prostate cancer (PCa) detection. Previously, TB has been found to increase the yield of clinically significant PCa and is more likely to sample the index tumor compared with traditional 12-core extended sextant biopsies. Currently, the prognostic significance of perineural invasion (PNI) when identified on TB (PNI-TB) is unknown. We identified 95 men at 2 tertiary referral centers who underwent TB followed by radical prostatectomy between January 2014 and January 2017. Clinical, radiological, and pathological variables were retrospectively reviewed. PNI was identified on TB in 27 of 95 (28.4%) patients. On multivariable logistic regression, independent predictors of extraprostatic extension were prostate-specific antigen, TB maximum % core involvement, and PNI-TB (all P<.05). Furthermore, Kaplan-Meier analysis demonstrated that PNI-TB was associated with early biochemical recurrence events within 12 months after prostatectomy (log-rank P=.049). Given the increasing adoption of TB for PCa detection in clinical practice, PNI-TB may be useful for PCa risk stratification.

Magnetic resonance imaging detection of prostate cancer in men with previous negative prostate biopsy.

Use of transrectal ultrasound guided systematic prostate biopsy has poor diagnostic accuracy for prostate cancer (PCa) detection. Recently multiparametric MRI (mpMRI) of the prostate and MR/US fusion biopsy has been gaining popularity for men who have previously undergone a negative biopsy. We performed PubMed® and Web of Science® searches to identify studies on this subject, particularly focusing on studies consisting of patients who have had at least one previously negative biopsy. Across the literature, when a suspicious lesion is found on mpMRI, MR/US fusion biopsy has consistently demonstrated higher detection rate for any PCa and clinically significant PCa (csPCa) compared to the traditional repeat systematic biopsy (SB) approach. Furthermore, anteriorly located tumors are frequently identified using MR targeted biopsy (TB), suggesting that an MR guided approach allows for increased accuracy for detecting tumors commonly missed by systematic biopsies. We conclude that men with a prior negative biopsy and continued suspicion of PCa should strongly be encouraged to get a prostate mpMRI prior to a repeat biopsy.

Cautery artifact understages urothelial cancer at initial transurethral resection of large bladder tumours.

INTRODUCTION: We sought to determine how frequently cautery (thermal) artifact precludes an accurate determination of stage at initial transurethral resection of bladder tumour (TURBT) of large bladder tumours. METHODS: We queried our institution's billing data to identify patients who underwent TURBT for large bladder tumours >5cm (CPT 52240) by two urologists at an academic centre from January 2009 through April 2013. Only patients who underwent initial-staging TURBT for urothelial cancer were included. Pathological reports were reviewed for stage, number of separate pathological specimens per TURBT, and presence of cautery artifact. Operative reports were reviewed for whether additional cold cup biopsies were taken of other suspicious areas of the bladder, resident involvement, and type of electrocautery. RESULTS: We identified 119 patients who underwent initial staging TURBT for large tumours. Cautery artifact interfered with accurate staging in 7/119 (6%) of cases. Of these, six patients underwent restaging TURBT, with 50% percent experiencing upstaging to T2 disease. Tumour size, tumour grade, whether additional cold cup biopsies were taken, number of separate pathological specimens sent, and resident involvement were not associated with cautery artifact (all p>0.05). Bipolar resection had a higher rate of cautery artifact 5/42 (12%), compared to monopolar resection 2/77 (2.6%) approaching significance (p=0.095). CONCLUSIONS: Cautery artifact may delay accurate staging at initial TURBT for large tumours by understaging up to 6% of patients.

Impact of Gleason Subtype on Prostate Cancer Detection Using Multiparametric Magnetic Resonance Imaging: Correlation with Final Histopathology.

PURPOSE: We determined whether Gleason pattern 4 architecture impacts tumor visibility on multiparametric magnetic resonance imaging and correlates with final histopathology. MATERIALS AND METHODS: A total of 83 tumor foci were identified in 22 radical prostatectomy specimens from patients with a prior negative biopsy who underwent magnetic resonance/ultrasound fusion biopsy followed by radical prostatectomy from January 2015 to July 2016. A genitourinary pathologist rereviewed tumor foci for Gleason architectural subtype. Each prostate imaging reporting and data system category 3 to 5 lesion on multiparametric magnetic resonance imaging was paired with its corresponding pathological tumor focus. Univariable and multivariable analyses were performed to determine predictors of tumor visibility. RESULTS: Of the 83 tumor foci identified 26 (31%) were visible on multiparametric magnetic resonance imaging, 33 (40%) were Gleason score 3+3 and 50 (60%) were Gleason score 3+4 or greater. Among tumor foci containing Gleason pattern 4, increasing tumor size and noncribriform predominant architecture were the only independent predictors of tumor detection on multivariable analysis (p = 0.002 and p = 0.011, respectively). For tumor foci containing Gleason pattern 4, 0.5 cm or greater, multiparametric magnetic resonance imaging detected 10 of 13 (77%), 5 of 14 (36%) and 9 of 10 (90%) for poorly formed, cribriform and fused architecture, respectively (p = 0.01). The size threshold for the detection of cribriform tumors was higher than that of other architectural patterns. Furthermore, cribriform pattern was identified more frequently on systematic biopsy than on targeted biopsy. CONCLUSIONS: Reduced visibility of cribriform pattern on multiparametric magnetic resonance imaging has significant ramifications for prostate cancer detection, surveillance and focal therapy.

Spontaneous Ureteral Urine Extravasation From Invasion of a High-grade Angiosarcoma.

A 69 year-old male with a past medical history of hypertension, diabetes, and atrial fibrillation presented to the Urology clinic with asymptomatic microscopic hematuria. His work up for hematuria included a negative cystoscopy and a computed tomography (CT) scan, which revealed what appeared to be a fluid collection around the left kidney with a perinephric infiltrative mass and two para-aortic enlarged lymph nodes.

Overexpression of the novel senescence marker ß-galactosidase (GLB1) in prostate cancer predicts reduced PSA recurrence.

PURPOSE: Senescence is a terminal growth arrest that functions as a tumor suppressor in aging and precancerous cells and is a response to selected anticancer compounds. Lysosomal-ß-galactosidase (GLB1) hydrolyzes ß-galactose from glycoconjugates and is the origin of senescence-associated ß-gal activity (SA-ß-gal). Using a new GLB1 antibody, senescence biology was investigated in prostate cancer (PCa) tissues. EXPERIMENTAL DESIGN: In vitro characterization of GLB1 was determined in primary prostate epithelial cell cultures passaged to replicative senescence and in therapy-induced senescence in PCa lines using chemotherapeutic agents. FFPE tissue microarrays were subjected to immunofluorescent staining for GLB1, Ki67 and HP1γ and automated quantitative imaging initially using AQUA in exploratory samples and Vectra in a validation series. RESULTS: GLB1 expression accumulates in replicative and induced senescence and correlates with senescent morphology and P16 (CDKN2) expression. In tissue arrays, quantitative imaging detects increased GLB1 expression in high-grade prostatic intraepithelial neoplasia (HGPIN), known to contain senescent cells, and cancer compared to benign prostate tissues (p<0.01) and senescent cells contain low Ki67 and elevated HP1γ. Within primary tumors, elevated GLB1 associates with lower T stage (p=0.01), localized versus metastatic disease (p=0.0003) and improved PSA-free survival (p=0.03). Increased GLB1 stratifies better PSA-free survival in intermediate grade PCa (0.01). Tissues that elaborate higher GLB1 display increased uniformity of expression. CONCLUSION: Increased GLB1 is a valuable marker in formalin-fixed paraffin-embedded (FFPE) tissues for the senescence-like phenotype and associates with improved cancer outcomes. This protein addresses a lack of senescence markers and should be applicable to study the biologic role of senescence in other cancers.