Abstract Background: Non-Hispanic Black American patients (BA) with prostate cancer (PCa) tend to fare worse than their Non-Hispanic White American counterparts (WA), even with consideration of socioeconomic disparities. Clinically, BA face diagnosis at younger age with worse clinical outcomes. Stromal cells adjacent to the tumor, including carcinoma-associated fibroblasts (CAFs), play a critical role in tumorigenesis of PCa. Dysfunction in the tumor microenvironment play a crucial role in mediating prostate cancer tumorigenesis and is emerging as a key target for cancer therapy in solid tumors. Methods: To investigate whether DNA methylation varies in tumor adjacent stroma (TAS) among PCa patients with different geographical ancestries, areas immediate adjacent to tumor (i.e., less than 1mm) removed for methylation analysis. A complete genome-wide DNA methylation of PCa stroma using 17 BA and 15 WA patients who had radical prostatectomy was carried out. Methyl-Captured (mCap) sequencing data was generated for TAS of prostate cancer FFPE tissues. Methylated sites were identified with the MACS2 callpeak function using a band width of 300 bp and a false discovery rate of q < 0.05. A consensus peak set was derived from the aligned reads of BA and WA prostate cancer stroma samples that were sequenced. Pathway analysis was performed using Ingenuity Pathway Analysis (IPA) tools. CAFs from primary tumors of BA and WA was prepared by tissue culture and treated with demethylating agent (i.e., 5-Azacytidine) for 24 hours followed by maintenance of the cells in drug-free medium for 7-10 days and subjected to mCap sequencing. Results: We found racial disparities in genome-wide DNA methylation in TAS between the two populations in which BA PCa patients had significantly increased in global DNA methylation as compared to their WA counterpart (p value < 0.001). Hypomethylation occurred in CAFs from BA patients treated with 5-Azacytidine. We identified 1041 methylated sites corresponding to 409 unique genes that were differentially methylated in BA vs WA (p value < 0.05). Pathway analysis identified significant association between methylated genes in BA TAS and immune response pathways including IL-13, JACK/STAT, T cell receptors, NF-KB, and PD-1, PDL1 cancer immunotherapy. Evaluation of the methylome profile between patients based on the post-prostatectomy resection margins, negative (R0) vs positive (R1), showed that R0 resections had significantly greater (p value < 0.001) methylation than R1 resections. Further analysis identified 984 sites corresponding to 373 differentially methylated, unique genes (p value < 0.05). Conclusion: Tumor-adjacent stroma of BA prostate cancer patients has a distinct methylome as compared to WA patients. Differences in immune response pathways suggests a distinct immune response in TAS in men of different races. Citation Format: Santosh Sankaran, James Nguyen, Tara Jennings, Vinay Kumar, Michael B. Lilly, Michael M. Ittmann, Patricia Castro, Liankun Song, Thomas Keane, Weiping Chu, Xiaolin Zi, Omid Yazdanpanah, Arash Rezazadeh Kalebasty, Farah Rahmatpanah. Tumor-microenvironment from African-American prostate cancer exhibit methylation of multiple immune modulators [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2148.

You have accessJournal of UrologyBladder Cancer: Non-invasive II (MP16)1 Sep 2021MP16-03 PHASE 3 STUDY OF VICINEUM IN BCG-UNRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER: 24-MONTH RESULTS Michael O'Donnell, Neal Shore, Thomas Keane, Michael Jewett, Rian Dickstein, Fred Wolk, Rachelle L. Dillon, Jeannick Cizeau, and Wassim Kassouf Michael O'DonnellMichael O'Donnell More articles by this author , Neal ShoreNeal Shore More articles by this author , Thomas KeaneThomas Keane More articles by this author , Michael JewettMichael Jewett More articles by this author , Rian DicksteinRian Dickstein More articles by this author , Fred WolkFred Wolk More articles by this author , Rachelle L. DillonRachelle L. Dillon More articles by this author , Jeannick CizeauJeannick Cizeau More articles by this author , and Wassim KassoufWassim Kassouf More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002001.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract WITHDRAWN © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e296-e297 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Michael O'Donnell More articles by this author Neal Shore More articles by this author Thomas Keane More articles by this author Michael Jewett More articles by this author Rian Dickstein More articles by this author Fred Wolk More articles by this author Rachelle L. Dillon More articles by this author Jeannick Cizeau More articles by this author Wassim Kassouf More articles by this author Expand All Advertisement Loading ...

BACKGROUND & AIMS:Extracorporeal shock wave lithotripsy (ESWL) for pancreaticolithiasis is most commonly performed by urologists. We investigated the effects of transitioning from urologist- to gastroenterologist-directed ESWL on case complexity, process measures, and duct clearance.METHODS:We performed a retrospective study of patients who underwent ESWL for pancreaticolithiasis from 2014 through 2019 at a single center. We collected demographic, clinical, radiographic, and procedural data in duplicate and compared case complexity and process measures between the periods the procedure was performed by urologists (January 2014 through February 2017; 18 patients, 0.47 patients/month) vs gastroenterologists (March 2017 through December 2019; 61 patients; 1.79 patients/month). We also compared data on pancreatic duct stone characteristics and technical success (duct clearance, determined by imaging analysis).RESULTS:There were no differences in patient demographics, comorbidities, pancreatic stone morphology, or time from referral to ESWL during the period the procedure was performed by urologists vs gastroenterologists. Patients received a higher mean number of ESWL shocks per session during the gastroenterology period (4341) than during the urology period (3117) (P < .001). A higher proportion of patients underwent same-session endoscopic retrograde cholangiopancreatography during the gastroenterology time period (66%) than the urology time period (6%) (P < .001). A higher proportion of patients had partial or complete duct clearance during the gastroenterology period (71%) than during the urology period (44%) (P = .04). During the urology period, a higher proportion of patients were hospitalized following ESWL, although there was no difference in captured adverse events between the periods.CONCLUSIONS:Transition from urologist- to gastroenterologist-directed ESWL did not affect case complexity or wait times for ESWL. However, the transition did result in increased procedure volume, more shocks per ESWL session, and improved duct clearance.

Prostate cancer (PCa) in Black Americans (BA) is diagnosed at an earlier median age and a more advanced stage than PCa in White Americans (WA). Tumor-adjacent stroma (TAS) plays a critical role in tumorigenesis of prostate cancer. We examined RNA expression in both tumor and TAS of BA compared to WA. After evaluating the geographical ancestry of each sample, preliminary analysis of our own RNA-seq data of 7 BA and 7 WA TAS revealed 1706 downregulated and 1844 upregulated genes in BA relative to WA PCa patients (p adj < 0.05). An assessment of published RNA-seq data of clinically matched tumor-enriched tissues from 15 BA and 30 WA patients revealed 932 upregulated and 476 downregulated genes in BA relative to WA (p adj < 0.05). When TAS and tumor epithelial cohorts were compared for the top 2500 statistically significant genes, immune responses were downregulated in BA vs WA TAS, while T cell-exhaustion pathways and the immune checkpoint gene CTLA4 were upregulated in BA vs WA tumors. We found fewer activated dendritic cells in tumor and more CD8 T-cells in TAS of BA versus WA PCa patients. Further characterization of these differences in the immune response of PCa patients of distinct geographical ancestry could help to improve diagnostics, prognostics, and therapy.

116 Background: Randomized trials have demonstrated a survival advantage to administering docetaxel (D) shortly after initiation of androgen deprivation therapy (ADT) in men with newly diagnosed hormone sensitive metastatic prostate cancer (hsMPC). Clinical trials in breast cancer, research in prostate cancer cell lines, and pharmacokinetic analyses of D clearance in the castrate state, suggest increased efficacy of chemotherapy administered separately from hormone suppression. We proposed that treatment with D before ADT might improve outcomes in newly diagnosed hsMPC. Methods: In an ongoing phase II study (NCT03069937), men with newly diagnosed hsMPC were treated with 4 cycles of D (75mg/m2) every 21 days without ADT followed by 2 cycles of D concurrent with the LHRH antagonist degarelix (Deg) administered every 4 weeks. The Deg alone was continued for a total of 7 injections. Men were trial eligible with high or low volume disease by CHAARTED criteria. Bicalutamide was allowed for < 30 days before trial entry, but LHRH directed therapy was not permitted. The primary endpoint for this trial is percentage of men obtaining PSA < 0.2 ng/ml. Pre-specified secondary endpoints examined here after 4 cycles of docetaxel alone are safety, and efficacy defined by PSA (decrease by > 50%) and radiographic responses. Results: At time of this abstract, 50 patients have been enrolled to trial. Two patients withdrew after 1 cycle of D, and 4 patients have not yet completed 4 cycles. Of the 50 patients evaluable for safety, 6 (12%) had Grade 3 toxicities related to D. No Grade 4/5 toxicities were reported. Of patients who completed 4 cycles of D, 24/44 (55%) had a PSA response and 34/44 (77%) had PSA decline from baseline. All but two patients with declining PSA had stable or improved radiographic imaging. Six of the 44 patients (14%) had PSA progression (>25% increase) with D therapy, 3 of whom also had radiographic progression. Every patient with PSA response after 4 cycles D had PSA decline after 2 cycles. No patient with PSA decline after 2 cycles had PSA progression after 4 cycles. PSA response rate was stratified by baseline variables in table below. Conclusions: In hsMPC patients, 4 cycles D without ADT appears to be a safe and active therapy. Treatment with bicalutamide prior to the start of D predicts poorer PSA response. This result strengthens our hypothesis that sensitivity of hsMPC to taxane therapy may be enhanced if ADT is postponed. Baseline genomics will be analyzed, and we hope to correlate responses to D alone with later primary efficacy outcomes. Clinical trial information: NCT03069937. [Table: see text]

PURPOSE:We evaluated the timeliness of androgen deprivation therapy dosing, the impact of dosing nonadherence on testosterone, and the frequency of testosterone and prostate specific antigen testing in patients with prostate cancer.MATERIALS AND METHODS:We retrospectively analyzed the records of 22,860 patients with prostate cancer treated with luteinizing hormone-releasing hormone agonists. Analyses were done using 2 definitions of month, including a 28-day month (late dosing after day 28, 84, 112 or 168) and an extended month (late after day 32, 97, 128 or 194) for 1, 3, 4 and 6-month formulations, respectively. The prevalence of late dosing, associated testosterone values, and the frequency of testosterone and prostate specific antigen testing were assessed. Statistical significance was assessed with the unpaired t-test.RESULTS:Of the injections 84% and 27% were late for the 28-day and extended month analyses, respectively. For the 28-day month 60% and 29% of injections were late by more than 1 and more than 2 weeks, respectively. Of testosterone values 4% were greater than 50 ng/dl for early/on time injections using both definitions, and 15% and 27% were greater than 50 ng/dl when late, and for the 28-day month and the extended month, respectively. For early/on time vs late injections 22% vs 31% of testosterone values were greater than 20 ng/dl for the 28-day month and 21% vs 43% for the extended month. Mean testosterone was higher when late (49 ng/dl for 28-day month, 79 ng/dl for extended month) vs early/on time (both 21 ng/dl). Of the injections prostate specific antigen measurements were performed in 83% and testosterone assessment was done in only 13%.CONCLUSIONS:Luteinizing hormone-releasing hormone agonists were frequently (84%) administered later than the schedules used in pivotal trials. Nearly half of the late testosterone values for the extended month were greater than 20 ng/dl and mean testosterone was almost double the castration level. Elevated testosterone remained unidentified with infrequent testing.

You have accessJournal of UrologyBladder Cancer: Non-invasive I (PD03)1 Apr 2020PD03-02 PHASE 3 RESULTS OF VICINIUM IN BCG-UNRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER Neal Shore*, Michael O'Donnell, Thomas Keane, Michael A.S. Jewett, Girish S. Kulkarni, Rian Dickstein, Fred Wolk, Curtis Dunshee, Laurence Belkoff, Rachelle L. Dillon, Jeannick Cizeau, and Wassim Kassouf Neal Shore*Neal Shore* More articles by this author , Michael O'Donnell Michael O'Donnell More articles by this author , Thomas Keane Thomas Keane More articles by this author , Michael A.S. JewettMichael A.S. Jewett More articles by this author , Girish S. KulkarniGirish S. Kulkarni More articles by this author , Rian DicksteinRian Dickstein More articles by this author , Fred WolkFred Wolk More articles by this author , Curtis DunsheeCurtis Dunshee More articles by this author , Laurence BelkoffLaurence Belkoff More articles by this author , Rachelle L. DillonRachelle L. Dillon More articles by this author , Jeannick CizeauJeannick Cizeau More articles by this author , and Wassim Kassouf Wassim Kassouf More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000823.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Alternatives to radical cystectomy (RC) are critically needed for the treatment of high-risk BCG-unresponsive NMIBC. Vicinium is a recombinant fusion protein comprised of an anti-EpCAM scFv linked to a variant of Pseudomonas exotoxin A (ETA). ETA mediates tumor cell death by blocking protein synthesis. Dying tumor cells display immunogenic cell death signals and neo-antigens known to promote an adaptive T-cell mediated anti-tumor response. Vicinium is being developed for the treatment of BCG-unresponsive NMIBC. METHODS: BCG-unresponsive NMIBC patients defined as refractory or relapsing within 6 months (n = 126) and relapsing within 6 to 11 months (n = 7) after adequate BCG therapy were accrued in a Phase 3 single-arm multicenter registrational trial (NCT02449239). During induction, Vicinium was instilled for 2 hours twice weekly for 6 weeks, then weekly for 6 weeks. Disease-free patients at 3 months received maintenance every 2 weeks for up to 2 years. Patients were assessed every 13 weeks, with a response defined as negative cytology along with normal cystoscopy or absence of high-grade disease on biopsy. RESULTS: As of May 29th 2019, the complete response rate of the evaluable carcinoma in situ (CIS) patients (n = 89) at 3 months was 40% and the median duration of response was 9.4 months (95% CI, 5.1-NE). Of the 3-month CIS responders, 52% remained disease-free for 12 months after starting treatment. The recurrence-free rates of the evaluable papillary patients (n = 38) at 3, 6, 12 and 24 months were 71, 58, 50 and 37%, respectively, and the median time to recurrence was 13.2 months (95% CI, 5.6-NE). Overall, responders at 3 months remained RC-free for 34.0 vs. 20.7 months for non-responders (p ≤ 0.001). Furthermore, the rate of RC was only 10% (6 of 63) for the 3-month responders versus 32% (18 of 56) for the non-responders. Preliminary overall survival was 96% (95% CI, 92-100) at 2 years. Vicinium was well-tolerated with only 52% of patients experiencing treatment-related adverse events (AEs), the majority being grade 1-2. Moreover, the AE frequency was similar between 54-69, 70-79 and 80-plus age groups. A total of 4 treatment-related severe AEs were reported in 3 patients and included grade 4 cholestatic hepatitis, grade 5 renal failure, grade 3 acute kidney injury and grade 2 pyrexia. Only 3% of the patients discontinued treatment due to AEs. CONCLUSIONS: This Phase 3 study showed that Vicinium was well-tolerated, demonstrated clinically meaningful anti-tumor activity and may delay and/or prevent RC. Source of Funding: Sesen Bio © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e72-e72 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Neal Shore* More articles by this author Michael O'Donnell More articles by this author Thomas Keane More articles by this author Michael A.S. Jewett More articles by this author Girish S. Kulkarni More articles by this author Rian Dickstein More articles by this author Fred Wolk More articles by this author Curtis Dunshee More articles by this author Laurence Belkoff More articles by this author Rachelle L. Dillon More articles by this author Jeannick Cizeau More articles by this author Wassim Kassouf More articles by this author Expand All Advertisement PDF downloadLoading ...

INTRODUCTION To interpret data and update the traditional categorization of prostate cancer in order to help treating clinicians make more informed decisions. These updates include guidance regarding how to best use next generation imaging (NGI) with the caveat that the new imaging technologies are still a work in progress. MATERIALS AND METHODS Literature review. RESULTS Critical goals in prostate cancer management include preventing or delaying emergence of distant metastases and progression to castration-resistant disease. Pathways for progression to metastatic castration-resistant prostate cancer (mCRPC) involve transitional states: nonmetastatic castration-resistant prostate cancer (nmCRPC), metastatic hormone-sensitive prostate cancer (mHSPC), and oligometastatic disease. Determination of clinical state depends in part on available imaging modalities. Currently, fluciclovine and gallium-68 (⁶⁸Ga) prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) are the NGI approaches with the most favorable combination of availability, specificity, and sensitivity. PET imaging can be used to help guide treatment selection in most patients. NGI can help determine patients who are candidates for new treatments, most notably (next-generation androgen antagonists, eg, apalutamide, enzalutamide, darolutamide), that can delay progression to advanced disease. CONCLUSIONS It is important to achieve a consensus on new and more easily understood terminology to clearly and effectively describe prostate cancer and its progression to health care professionals and patients. It is also important that description of disease states make clear the need to initiate appropriate treatment. This may be particularly important for disease in transition to mCRPC.

Purpose:The advanced prostate cancer therapeutic landscape has changed dramatically in the last several years, resulting in improved overall survival of patients with castration naive and castration resistant disease. The evolution and development of novel next generation imaging techniques will affect diagnostic and therapeutic decision making. Clinicians must navigate when and which next generation imaging techniques to use and how to adjust treatment strategies based on the results, often in the absence of correlative therapeutic data. Therefore, guidance is needed based on best available information and current clinical experience.Materials and Methods:The RADAR (Radiographic Assessments for Detection of Advanced Recurrence) III Group convened to offer guidance on the use of next generation imaging to stage prostate cancer based on available data and clinical experience. The group also discussed the potential impact of next generation imaging on treatment options based on earlier detection of disease.Results:The group unanimously agreed that progression to metastatic disease is a seminal event for patient treatment. Next generation imaging techniques are able to detect previously undetectable metastases, which could redefine the phases of prostate cancer progression. Thus, earlier systemic or locally directed treatment may positively alter patient outcomes.Conclusions:The RADAR III Group recommends next generation imaging techniques in select patients in whom disease progression is suspected based on laboratory (biomarker) values, comorbidities and symptoms. Currently F-18-fluciclovine and Ga-68 prostate specific membrane antigen positron emission tomography/computerized tomography are the next generation imaging agents with a favorable combination of availability, specificity and sensitivity. There is ongoing research of additional next generation imaging technologies, which may offer improved diagnostic accuracy and therapeutic options. As next generation imaging techniques evolve and presumably result in improved global accessibility, clinician ability to detect micrometastases may be enhanced for decision making and patient outcomes.

Background: A combined clinical cell-cycle risk (CCR) score that incorporates prognostic molecular and clinical information has been recently developed and validated to improve prostate cancer mortality (PCM) risk stratification over clinical features alone. As clinical features are currently used to select men for active surveillance (AS), we developed and validated a CCR score threshold to improve the identification of men with low-risk disease who are appropriate for AS. Methods: The score threshold was selected based on the 90th percentile of CCR scores among men who might typically be considered for AS based on NCCN low/favorable-intermediate risk criteria (CCR = 0.8). The threshold was validated using 10-year PCM in an unselected, conservatively managed cohort and in the subset of the same cohort after excluding men with high-risk features. The clinical effect was evaluated in a contemporary clinical cohort. Results: In the unselected validation cohort, men with CCR scores below the threshold had a predicted mean 10-year PCM of 2.7%, and the threshold significantly dichotomized low- and high-risk disease (P = 1.2 x 10(-5)). After excluding high-risk men from the validation cohort, men with CCR scores below the threshold had a predicted mean 10-year PCM of 2.3%, and the threshold significantly dichotomized low- and high-risk disease (P = 0.020). There were no prostate cancer-specific deaths in men with CCR scores below the threshold in either analysis. The proportion of men in the clinical testing cohort identified as candidates for AS was substantially higher using the threshold (68.8%) compared to clinicopathologic features alone (42.6%), while mean 10-year predicted PCM risks remained essentially identical (1.9% vs. 2.0%, respectively). Conclusions: The CCR score threshold appropriately dichotomized patients into low- and high-risk groups for 10-year PCM, and may enable more appropriate selection of patients for AS. (C) 2018 Elsevier Inc. All rights reserved.

You have accessJournal of UrologyImaging/Radiology: Uroradiology II1 Apr 2018MP20-17 CENTRAL ABDOMINAL UPTAKE ON INDIUM-111 CAPROMAB PENDETIDE IMAGING: A POWERFUL PROGNOSTIC INDICATOR FOR PROSTATE CANCER IN HIGH-RISK PATIENTS AND IN THE SETTING OF BIOCHEMICAL RECURRENCE Goran Rac, Shepherd Caitlin, Sarah Starosta, Barry Keane, Sam Keane, William Rieter, and Thomas Keane Goran RacGoran Rac More articles by this author , Shepherd CaitlinShepherd Caitlin More articles by this author , Sarah StarostaSarah Starosta More articles by this author , Barry KeaneBarry Keane More articles by this author , Sam KeaneSam Keane More articles by this author , William RieterWilliam Rieter More articles by this author , and Thomas KeaneThomas Keane More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.687AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Indium-111 Capromab Pendetide (ProstaScint) is a monoclonal PSMA-based imaging modality used at our institution for the evaluation of newly diagnosed high-risk prostate cancer and in patients with biochemical recurrence after definitive treatment. Central abdominal update (CAU) on ProstaScint has been found to be a poor prognostic indicator; however, there is a paucity of long term data on the subject. We present over 10 years' experience utilizing ProstaScint to assess the relationship between CAU and prostate cancer treatment failure. METHODS We performed a retrospective analysis of 187 patients diagnosed with CAU on ProstaScint scan obtained for either high-risk prostate cancer or evaluation for salvage therapy between December 2003 and December 2011. A total of 50 patients with long term follow-up were identified. Of these, 36 patients underwent salvage therapy after biochemical recurrence. The remaining 14 patients underwent Prostascint scan for high-risk prostate cancer prior to primary intervention. There was a mean length of follow up of 8.6 years. RESULTS Overall, 86% (43/50) of patients with CAU failed either primary or salvage treatment of prostate cancer. Half (7/14) of the patients with CAU on a scan for high-risk prostate cancer prior to undergoing primary intervention failed initial treatment. All 36 patients scanned for biochemical recurrence failed salvage treatment. Average time to recurrence after initial or salvage treatment was 3.6 years, with 67.4% (29/43) of patients with early recurrence less than 3 years after treatment. Over half (26/50) of patients with CAU required subsequent radiation therapy: 9 undergoing radiation alone and 17 undergoing combined radiation and androgen depravation therapy with treatment failures of 100% (9/9) and 76.6% (13/17), respectively. 89.2% (33/37) of patients with 5-year follow-up had treatment failure. All 19 patients with 10-year follow-up had treatment failure. CONCLUSIONS In our cohort of patients, the presence of CAU on Prostascint imaging correlated with failure of both primary and salvage interventions. Patients with CAU had an earlier time to recurrence. The majority of patients at 5 years and all patients at 10 years failed prostate cancer treatment. We confirm that CAU on Prostascint imaging is associated with poor outcomes and responses to both primary and salvage therapy. Imaging with ProstaScint should be considered in patients with high-risk prostate cancer as well as those with biochemical recurrence prior to salvage therapies. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e260 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Goran Rac More articles by this author Shepherd Caitlin More articles by this author Sarah Starosta More articles by this author Barry Keane More articles by this author Sam Keane More articles by this author William Rieter More articles by this author Thomas Keane More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Androgen deprivation therapy (ADT) is a mainstay of treatment for advanced prostate cancer. Several studies have reported an association between ADT and an increase in cardiovascular events, especially in those receiving gonadotropin-releasing hormone (GnRH) agonists compared to GnRH antagonists. We review the body of literature reporting the association of ADT and cardiovascular morbidity, and discuss the proposed mechanism of cardiovascular disease due to ADT including metabolic changes that may promote atherosclerosis and local hormonal effects that may increase plaque rupture and thrombosis.

OBJECTIVE:To offer recommendations on identification of disease progression, treatment management strategies, and suggestions on timing of initiating and discontinuing specific castration-resistant prostate cancer (CRPC) treatments.MATERIALS AND METHODS:The Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence II Working Group convened to provide guidance on sequencing, combination, or layering of approved treatments for metastatic CRPC based on available data and clinical experience.RESULTS:A consensus was developed to address important questions on management of patients with metastatic CRPC.CONCLUSION:In the absence of large-scale clinical trials, the Working Group recommends that patients may best be managed with a layered approach of approved therapies with unique or complimentary mechanisms of action.

Study design, materials and methods Following IRB approval, we performed a review of patients who underwent RALP or RPP from 2009-2015 at a single institution. One surgeon performed all RPPs and 4 surgeons performed all RALPs. We compared baseline demographics, perioperative data, and post-operative outcomes including International Prostate Symptom Score (IPSS), quantitative pad use, continence rates defined as no pad use on follow-up visit, and voiding dysfunction interventions at 3, 6, 9, 12, 24 and 60 months.

PURPOSE:To explore how follicle-stimulating hormone (FSH) may contribute to cardiovascular, metabolic, skeletal, and cognitive events in men treated for prostate cancer, with various forms of androgen deprivation therapy (ADT). MATERIALS AND METHODS:A colloquium of prostate cancer experts was convened in May 2015, to discuss the role of FSH in the development of unwanted effects associated with ADT. Subsequently, a literature review (Medline, PubMed, and relevant congress abstract databases) was performed to further explore and evaluate the collected evidence. RESULTS:It has become evident that, in the setting of ADT, FSH can promote the development of atherosclerotic plaque formation, metabolic syndrome, and insulin resistance. Data also suggest that FSH is an important mediator of bone remodeling, particularly bone resorption, and thereby increases the risk for bone fracture. Additional evidence implicates a role for FSH in bone metastasis as well. The influence of FSH on ADT-induced cognitive deficits awaits further elucidation; however, the possibility that FSH may be involved therein cannot be ruled out. CONCLUSIONS:The widespread molecular and physiological consequences of FSH system activation in normal and pathological conditions are becoming better understood. Progress in this area has been achieved by the development of additional investigative and clinical measures to better evaluate specific adverse effects. More research is needed on FSH function in the development of cancer as well as its association with cardiovascular, metabolic, musculoskeletal, and cognitive effects in ADT.

You have accessJournal of UrologyProstate Cancer: Staging II1 Apr 2017PD61-08 DOES GLEASON SCORE AT THE SITE OF POSITIVE SURGICAL MARGIN PREDICT RECURRENCE FOLLOWING RADICAL PROSTATECTOMY? Goran Rac, Lawrence Dagrosa, Laura Spruill, and Thomas Keane Goran RacGoran Rac More articles by this author , Lawrence DagrosaLawrence Dagrosa More articles by this author , Laura SpruillLaura Spruill More articles by this author , and Thomas KeaneThomas Keane More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2767AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Multiple pathologic features have been shown to predict biochemical recurrence (BCR) in patients after radical prostatectomy (RP) for prostate cancer. While positive surgical margins (PSM) have been shown to increase the likelihood of BCR, little data exists on the clinical significance of the tumor Gleason grade at the site of PSM. This study aims to assess if the Gleason grade at the PSM is predictive of BCR, and whether its predictive value differs from that of other commonly referenced risk factors. METHODS We performed a retrospective review of a prospectively maintained database of all patients who underwent RP at our institution from 2009 to 2015. We identified 403 patients, 58 (14.4%) of whom were noted to have PSM. These cases were reviewed by an attending Pathologist who assigned a Gleason grade (3, 4 or 5) to the tumor at the site of PSM. The predictive value for BCR was compared to that of final pathology Gleason score and presence of PSM alone. RESULTS We found that 34.5% (20/58) of patients with PSM had BCR, which was greater than the overall BCR rate of 19.9% (80/403) (p < 0.0001). Patients with Gleason 4+ disease at the PSM had a higher BCR rate (57.9%, 11/19) compared to those with Gleason 3 (23.1%, 9/39, p = 0.009) and those with a negative margin (17.4%, 60/345, p < 0.0001). Interestingly, patients with Gleason 3 at the PSM did not have a significantly higher BCR rate than those with a negative margin. Gleason grade at the PSM was an independent predictor of BCR compared to presence of PSM alone. In patients with Gleason sum 7 disease on traditional final pathology, those with Gleason 3 at the PSM had a lower BCR rate (25.0%, 8/32) compared to those with Gleason 4+ (58.8%, 10/17, p = 0.02). CONCLUSIONS Our data suggests that Gleason score at the site of PSM independently predicts BCR in patients following RP with accuracy similar to traditional pathologic staging. However, in patients with a PSM and Gleason 7 on traditional pathologic staging, the presence of Gleason 4 or tertiary 5 disease at the margin can serve as an independent predictor of BCR, relative to patients with Gleason 3 at the margin. Routine reporting of the Gleason score at the site of a positive surgical margin may aid in postoperative risk stratification following RP. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1190-e1191 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Goran Rac More articles by this author Lawrence Dagrosa More articles by this author Laura Spruill More articles by this author Thomas Keane More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

You have accessJournal of UrologyProstate Cancer: Localized: Active Surveillance I1 Apr 2017PD28-02 THE IMPACT OF CLINICAL CCP TESTING IN MEN WITH LOCALIZED PROSTATE CANCER FOR EXPANDING THE POPULATION OF MEN ELIGIBLE FOR ACTIVE SURVEILLANCE Behfar Ehdaie, Steve Stone, Ryan Bernhisel, James Eastham, Thomas Keane, John Davis, E David Crawford, Michael Brawer, Daniel Lin, and Peter Scardino Behfar EhdaieBehfar Ehdaie More articles by this author , Steve StoneSteve Stone More articles by this author , Ryan BernhiselRyan Bernhisel More articles by this author , James EasthamJames Eastham More articles by this author , Thomas KeaneThomas Keane More articles by this author , John DavisJohn Davis More articles by this author , E David CrawfordE David Crawford More articles by this author , Michael BrawerMichael Brawer More articles by this author , Daniel LinDaniel Lin More articles by this author , and Peter ScardinoPeter Scardino More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1236AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Active surveillance (AS) is an established treatment modality for select men with prostate cancer (PC). Eligibility criteria are based on clinicopathologic features including PSA and Gleason grade. Prior studies have validated a combined cell-cycle progression risk (CCR) score, which combines cell-cycle progression (CCP) gene expression data with the Cancer of the Prostate Risk Assessment (CAPRA) score to add significant prognostic discrimination to newly diagnosed PCs. Our objective was to assess the value of the CCR score for identifying men with higher risk clinicopathologic characteristics who qualify for AS. METHODS Prostate biopsy samples from 17,017 men were submitted by their physicians for CCP testing (Myriad Genetic Laboratories). The CCP score was calculated from RNA expression of 46 genes (31 CCP and 15 housekeeping genes), and combined with CAPRA to generate the CCR score. Clinicopathological data was obtained from physician-completed test request forms. A threshold CCR score of 0.8 was previously developed and validated in a cohort of conservatively managed men (survival data censored at 10 yrs). We evaluated the proportion of men eligible for AS based on their CCR score whose clinicopathologic criteria would traditionally disqualify them from AS: PSA>10ng/mL, Gleason grade group≥2 (Gleason Score ≥3+4), higher AUA risk. RESULTS Overall, 66.6% of clinically tested men qualified for AS based on their CCR score. Table 1 shows that a proportion of tested men with higher risk clinicopatholic features qualified for AS based on their CCR score, including AUA intermediate (42.9%) and high (14.1%) risk as well as Gleason grade group 2 (48.8%) and Gleason grade group >2 (1-3%). In addition, 48% of men with Gleason score 6 and PSA >10 ng/mL qualified for AS. CONCLUSIONS Clinical characteristics and Gleason grade are often used as stand-alone indicators to offer men with localized PC immediate definitive treatment rather than AS. However, our study demonstrates that a significant proportion of men who qualify for AS based on their CCR score have a range of PSA and Gleason grade prostate cancer that may not traditionally be considered for AS. This supports using CCR score to improve risk stratification in PC and identify men for AS. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e517 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Behfar Ehdaie More articles by this author Steve Stone More articles by this author Ryan Bernhisel More articles by this author James Eastham More articles by this author Thomas Keane More articles by this author John Davis More articles by this author E David Crawford More articles by this author Michael Brawer More articles by this author Daniel Lin More articles by this author Peter Scardino More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...