Center For Prostate Disease Research Research Articles

MP40-01 DIFFERENTIALLY EXPRESSED GLYCOPROTEINS IN PRE- AND POST- DIGITAL RECTAL EXAMINATION URINE SAMPLES FOR DETECTING AGGRESSIVE PROSTATE CANCER

You have accessJournal of UrologyCME1 Apr 2023MP40-01 DIFFERENTIALLY EXPRESSED GLYCOPROTEINS IN PRE- AND POST- DIGITAL RECTAL EXAMINATION URINE SAMPLES FOR DETECTING AGGRESSIVE PROSTATE CANCER Indu Kohaar, Yuefan Wang, Tung-Shing Mamie Lih, Naseruddin Höti, Lori Sokoll, Gregory Chesnut, Gyorgy Petrovics, and Hui Zhang Indu KohaarIndu Kohaar More articles by this author , Yuefan WangYuefan Wang More articles by this author , Tung-Shing Mamie LihTung-Shing Mamie Lih More articles by this author , Naseruddin HötiNaseruddin Höti More articles by this author , Lori SokollLori Sokoll More articles by this author , Gregory ChesnutGregory Chesnut More articles by this author , Gyorgy PetrovicsGyorgy Petrovics More articles by this author , and Hui ZhangHui Zhang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003278.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer (PCa) is predominantly indolent disease with a small fraction of patients undergoing metastatic progression. Therefore, it is critical to identify non-invasive diagnostic markers for the early detection of an aggressive PCa subtype. We hypothesized that non-invasive pre-digital rectal examination (pre-DRE) urine specimens harbor molecular signatures of aggressive PCa, which can help in the clinical management of the disease. Previously, we had systematically evaluated urinary glycoproteins associated with aggressive prostate cancer (AG-PCa) using post-DRE urine specimens. The goal of the study is to explore the potential of using pre-DRE urine specimens for detecting AG-CaP and validate the post-DRE findings. METHODS: This is a retrospective case cohort study based on 154 pre-DRE urine specimens collected by the Center for Prostate Disease Research under an institutional review board approved protocol from men undergoing diagnostic biopsy. We performed an optimized quantitative mass spectrometric analysis to evaluate the association of markers with aggressive PCa at diagnosis. The cohort comprised 41 patients with no cancer at biopsy, 48 patients with non-AG-PCa (Gleason score=6), and 65 patients with AG-PCa (Gleason score 7 or above). Targeted analyses of AG-PCa-associated glycoproteins previously identified in post-DRE urine samples were also applied to validate the post-DRE findings in non-DRE specimens. Data-independent acquisition mass spectrometry (DIA-MS) analysis was performed for glycosite-containing peptides. Fisher exact and Wilcoxon-Mann-Whitney tests were used for categorical and continuous variables respectively and logistic regression was evaluated using receiver operating characteristic (ROC) analysis for the urinary markers and marker panels. RESULTS: Urinary prostatic acid phosphatase (ACPP), CD97 antigen (CD97), and prostate-specific antigen (PSA) levels in pre-DRE specimens were associated with patients with AG-PCa compared to cancer-negative and non-AG-PCa. The analysis confirmed three of the previously reported post-DRE urinary glycoproteins and identified three new AG-PCa-associated glycoproteins including Fibrillin 1 (FBN1), Vitronectin (VTN) and Hemicentin 2 (HMCN2). A multi-marker panel composed of urinary PSA, VTN, HMCN2, CD97 achieved an AUC of 0.78 (p=2.69 × 10-9) for distinguishing AG-PCa from cancer-negative & Gleason 6. Analysis of differentially abundant glycopeptides in pre- and post-DRE samples showed that compared to glycopeptides from the post-DRE urine data, humoral immunity-related proteins were enriched in pre-DRE urine samples, whereas immune cell-related proteins were enriched in post-DRE urine samples. CONCLUSIONS: Comparisons between post-DRE and pre-DRE urine specimens for glycoproteins have shown that pre-DRE samples hold promise for a non-invasive and simple early option for AG-PCa detection in patients. The identified AG-PCa-associated glycoproteins may be further evaluated in large cohort of pre-DRE urine specimens for detecting clinically significant prostate cancer. Source of Funding: NCI/EDRN IAA No. ACN 17005-001-0000011 (Gregory Chesnut) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e545 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Indu Kohaar More articles by this author Yuefan Wang More articles by this author Tung-Shing Mamie Lih More articles by this author Naseruddin Höti More articles by this author Lori Sokoll More articles by this author Gregory Chesnut More articles by this author Gyorgy Petrovics More articles by this author Hui Zhang More articles by this author Expand All Advertisement PDF downloadLoading ...

Race-specific prostate cancer outcomes in a cohort of military health care beneficiaries undergoing surgery: 1990-2017.

There is substantial variability in prostate cancer (PCa) mortality rates across Caucasian American (CA), African American (AA), Asian, and Hispanic men; however, these estimates are unable to disentangle race or ethnicity from confounding factors. The current study explores survival differences in long-term PCa outcomes between self-reported AA and CA men, and examines clinicopathologic features across self-reported CA, AA, Asian, and Hispanic men. This retrospective cohort study utilized the Center for Prostate Disease Research (CPDR) Multi-center National Database from 1990 to 2017. Subjects were consented at military treatment facilities nationwide. AA, CA, Asian, or Hispanic men who underwent radical prostatectomy (RP) for localized PCa within the first year of diagnosis were included in the analyses. Time from RP to biochemical recurrence (BCR), BCR to metastasis, and metastasis to overall death were evaluated using Kaplan-Meier unadjusted estimation curves and adjusted Cox proportional hazards regression. This study included 7067 men, of whom 5155 (73%) were CA, 1468 (21%) were AA, 237 (3%) were Asian, and 207 (3%) were Hispanic. AA men had a significantly decreased time from RP to BCR compared to CA men (HR=1.25, 95% CI=1.06-1.48, p=0.01); however, no difference was observed between AA and CA men for a time from BCR to metastasis (HR=0.73, 95% CI=0.39-1.33, p=0.302) and time from metastasis to overall death (HR=0.67, 95% CI=0.36-1.26, p=0.213). In an equal access health care setting, AA men had a shorter survival time from RP to BCR, but comparable survival time from BCR to metastasis and metastasis to overall death.

Prospective quality of life in men choosing open vs. robotic radical prostatectomy: long-term results from a racially diverse multi-institutional database.

To compare 5-year health-related quality of life (HRQoL) outcomes between prostate cancer (CaP) patients who underwent robotic-assisted laparoscopic radical prostatectomy (RALP) versus open radical retropubic prostatectomy (RRP) and assess for racial disparities between Caucasian American (CA) and African American (AA) men undergoing surgery. A prospective cohort study of HRQoL data was conducted on patients diagnosed with CaP from 2007 to 2017 and enrolled in the Center for Prostate Disease Research (CPDR) Multicenter National Database. Using the EPIC and SF-36 instruments, changes in urinary, sexual, bowel, and hormonal domains, as well as physical and mental component summary scores were compared across surgery type (RALP versus RRP) at pre-treatment ("baseline"), and annually for 5years. We further compared HRQoL outcomes in CA and AA men undergoing surgery. Longitudinal HRQoL patterns were modeled using generalized estimating equations (GEE), adjusting for baseline HRQoL and other characteristics. 448 CaP patients (22% AA) met study inclusion criteria, 66% underwent RALP and 34% underwent RRP. At baseline, HRQoL domains were comparable across treatment group (RALP vs. RRP). In the adjusted low-risk cohort, there were only three time points that met a statistically significant HRQoL difference in EPIC scores between RALP and RRP. Urinary function score during year 4 of follow-up showed a 7.5 (95% CI 3.1-11.9, P = 0.01) points difference in favor of RRP. Bowel bother scores favored RRP in year 1 with a difference of 3.1 (95% CI 0.7-5.4, P = 0.04) points, and in year 5 with a difference of 3.8 (95% CI 1.1-6.4, P = 0.03) points. In the intermediate/high-risk cohort, there were no statistically significant differences in any of the domain scores between RALP and RRP during follow-up. The robotic and open approach to radical prostatectomy led to comparable HRQoL outcomes at a follow-up length of 60months. No HRQoL racial disparities were found between AA and CA men during long-term follow-up.

The 17-Gene Genomic Prostate Score Test as a Predictor of Outcomes in Men with Unfavorable Intermediate Risk Prostate Cancer

To evaluate the association of the Genomic Prostate Score (GPS) assay result with biochemical recurrence (BCR), distant metastases (DM), and prostate-specific death (PCD) in unfavorable intermediate (UFI) risk prostate cancer patients. The GPS assay is used to help guide management decisions for newly diagnosed low and favorable intermediate (FI) risk disease. GPS results from 2 studies (Center for Prostate Disease Research [CPDR]; Kaiser Permanente Northern California [KPNC]) in men treated with radical prostatectomy were analyzed to determine associations of the GPS result with BCR, DM, and PCD in UFI risk disease. Analyses included 299 intermediate risk prostate patients, 175 of whom had UFI risk disease (KPNC=103; CPDR=72). The GPS result as a dichotomous value (≤40 vs >40) was a significant predictor of BCR in UFI patients in multivariate analyses (hazard ratio [HR] 6.0; 95% confidence interval [CI] 2.0-22.4; P=.0035; CPDR). The GPS result was a strong predictor of all 3 endpoints in multivariate analyses (BCR HR 7.1; 95% CI 5.7-8.8; P < .0001; DM HR 5.4; 95% CI 3.8-7.8; P < .0001; PCD HR 3.4; 95% CI 1.5-8.9; P=.006; KPNC). UFI patients with GPS >40 had outcomes consistent with high-risk disease, whereas UFI patients with GPS ≤40 had outcomes similar to FI risk patients (CPDR/KPNC). The GPS result was a strong independent predictor of BCR, DM, and PCD in intermediate risk prostate cancer. UFI patients with GPS >40 have a poor prognosis and may benefit from additional therapeutic options.

Abstract A108: Longitudinal trends in distant metastasis at diagnosis in a racially diverse cohort of prostate cancer patients: 1990-2017

Abstract Introduction: Concerns for overdetection and overtreatment of clinically insignificant PCa have led to changes in PSA screening recommendations. In 2008, the US Preventive Services Task Force (USPSTF) gave PSA screening a “Grade D” recommendation for older men (≥ 75 years), and in 2012 this was extended to men of all ages. In 2017, a draft of revised guidelines was released, elevating the letter Grade to C for men aged 55-69 years. Yet three compelling studies have revealed increases in the diagnosis of metastatic PCa (mPCa) in US men. The primary aim of this study was to examine time trends in mPCa at time of diagnosis, over a 25+ year study period, in a racially diverse longitudinal cohort with equal access to health care. Methodology: The Center for Prostate Disease Research (CPDR) Multi-Center National Database was the source of patients for this study. Men under suspicion for PCa who underwent TRUS-guided biopsy for PCa detection were eligible for enrolment into this database. This study focused on those with biopsy-confirmed PCa between January 1, 1990-December 31, 2017. Trends in mPCa at the time of diagnosis were examined for the overall cohort, as well as stratified by race (AA and CA) and patient age at CaP diagnosis (&amp;lt;75 years versus ≥75 years). Poisson regression with a log link function was used to estimate annual percent change (APC) in mPCa at diagnosis, as a proportion of all newly diagnosed PCa per annum. Multivariable logistic regression was used to model predictors of mPCa at diagnosis as a function of PSA screening intensity prior to CaP detection and patient race. Results: A total of 15,660 subjects met the study criteria, of whom 560 (2.8%) presented with mPCa. The decline in APC over time for the overall cohort was statistically significant (APC = -7.7%, p &amp;lt;0.0001). When APCs were computed for across race, both AA and CA patients were observed to have statistically significant declines over time in APCs (-10.2%, p&amp;lt;0.0001 and -7.1 %, p &amp;lt;0.0001, respectively). However, these declines were comparable across race (p=0.07). When stratified by age group, patients ≥75 years had a smaller magnitude of decline in APC compared to those &amp;lt;75 years (-2.7%, p&amp;lt;0.0001 and -9.2%, p&amp;lt;0.0001, respectively), though these declines did not differ significantly by age group (p=0.56). In multivariable analysis, both the number of prior PSA screenings (OR≥4 vs. None = 0.42, CI=0.29, 0.61, p &amp;lt;0.0001) but not self-reported race (ORAA vs. CA=1.1, CI=0.83, 1.36, p=0.65) predicted mPCa. Conclusions: In this longitudinal, racially diverse cohort with equal health care access, significant declines in mPCa at diagnosis were observed over a 25+ year study period. This is contrast to other recent studies that have demonstrated increases in mPCa following changes in USPSTF guidelines. There was, however, a difference in the magnitude of decrease in oldest patients (≥75 years) compared to younger men (&amp;lt;75 years) that may have been influenced by changes in PSA screening recommendations. Continued attention to shifts in mPCa at diagnosis is needed. Citation Format: Jennifer Cullen, John McCauley, Huai-ching Kuo, Yongmei Chen, Sean Stroup, John Musser, Christopher Porter, Timothy Brand, Kevin Rice, Shiv Srivastava, Inger Rosner, Grace Lu-ao. Longitudinal trends in distant metastasis at diagnosis in a racially diverse cohort of prostate cancer patients: 1990-2017 [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A108.

Abstract B075: Defining germline mutations of DNA damage repair genes in African American prostate cancer patients

Abstract Background: DNA damage repair genes (DDRGs) play a critical role in protecting genome integrity and have been implicated in several cancer types. In the context of prostate cancer (CaP) emerging data provide potential role of this pathway in aggressive disease. It has also been recently demonstrated that PARP inhibitors can extend overall survival in metastatic patients with DDRG mutations. However, the association and therapeutic stratification based on inherited mutations of DDRGs remains to be defined in African American (AA) CaP patients. Our objective was to assess the frequency and association with disease aggressiveness of all known DDRGs in blood derived genomic DNAs of AA and Caucasian American (CA) CaP patients archived at the DOD Center for Prostate Disease Research and assess how this information can refine patient stratification for specific targeted therapeutic options. Method: Germline mutations in all DDRGs was evaluated by whole genome sequence (WGS) analysis of archived blood DNA samples from 600 CaP patients (300 AA and 300 CA) who underwent primary treatment at Walter Reed National Military Medical Center (WRNMMC) over the past 20 years. These patients had equal access Department of Defense healthcare system with up to 20 years of follow-up time. Following quality control steps to assess DNA quantity by Qubit assay and DNA quality by Bioanalyzer assay, DNA samples were used to generate PCR-free libraries for WGS using the NovaSeq (Illumina) platform. Out of the 600 libraries we generated, 14 dropped out, achieving a success rate of 97.6%. The successful libraries had an excellent quality based on DNA library metrics (yield and fragment length). Whole genome sequencing depth of the samples exceeded 37x on average and about 4 million SNPs were identified in the samples. Patient genotypes were projected onto principal components from reference populations. Sample ancestries were predicted by using the “Peddy” program, which uses a machine learning model trained on individuals of diverse ancestries from the 1000 Genomes Project reference panel. Due to mismatched ancestry, 33 samples were excluded from further analyses. An additional 17 samples were excluded due to higher than minimal noise level based on analyses using “ContEst” tool from Broad GATK package and Illumina noise percent values. Results: Interrogation of an inclusive DDRG set of 180 genes predicted to have non-silent effects on the protein sequence (e.g. missense, nonsense, frameshift) for germline mutations in this cohort revealed several known and novel mutations. The analysis has not been finalized yet. Mutation data will be assessed for association with the extensive available clinical and pathological data, including disease progression (metastasis), family history and African ancestry. Novel mutations, anticipated especially in the understudied AA context, will be analyzed for functional impact. Citation Format: Kevin Babcock, Xijun Zhang, Matthew Wilkerson, Clifton L. Dalgard, Shyh-Han Tan, Lakshmi Ravindranath, Yongmei Chen, Jennifer Cullen, Shiv Srivastava, Inger L. Rosner, Gyorgy Petrovics. Defining germline mutations of DNA damage repair genes in African American prostate cancer patients [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B075.

Long-term prospective health related quality of life (HRQoL) outcomes: Impact of active surveillance before treatment of low risk prostate cancer (PCa).

e17518 Background: The treatment options for low risk PCa are active surveillance (AS), radiation therapy (RT), and radical prostatectomy (RP). HRQoL studies with long term follow up are lacking. We evaluated HRQoL of initial active surveillance vs initial treatment. Methods: The Center for Prostate Disease Research (CPDR) database was used. HRQoL data was collected for 5 years with the Expanded Prostate Cancer Index Composite (EPIC) and the 36-item Medical Outcomes Study Short Form (SF-36). Patients had low risk PCa, age less than 75, and follow up data of at least 1 year. AS was defined as no definitive treatment within 12 months of diagnosis and repeat biopsy or PSA within 18 months of diagnosis. Results: Patient characteristics are located in the table. Baseline HRQoL scores were comparable across treatment groups for all HRQoL domains, except for sexual function and bother, and physical health where RT were worse than RP. Of the 68 patients classified as AS, 4 had brachytherapy, 9 had hormone therapy, 38 had RP, and 17 had XRT as a first treatment after terminating their AS. In the Generalized Estimating Equations (GEE) model, the HRQoL scores were compared. Multivariate analysis was done accounting for baseline differences. Urinary function (p = 0.0017), urinary bother (p = 0.0028), hormone function (p = 0.035), bowel bother (p = 0.0122), sexual function (p &lt; 0.01), sexual bother (p &lt; 0.01), and physical health (p = 0.0457) were significantly different. For urinary function and bother, XRT had the best HRQoL scores at most time points, with AS getting worse over time as patients went on to receive treatment. AS had worse scores with hormone function and sexual function. RP had the best scores for bowel bother over the course of the study, but had the worst initial scores in sexual bother, which got better over time. Hormone bother (p = 0.5574), Bowel function (p = 0.098), mental health (p = 0.7231) were not statistically different between groups. Conclusions: Initially AS results in improved HRQoL. For those patients who undergo treatment after AS, HRQoL is no worse than those who got treatment initially. [Table: see text]

A prospective analysis of health-related quality of life in intermediate and high-risk prostate cancer patients managed with intensity modulated radiation therapy, with vs. without hormonal therapy

Combined radiotherapy and hormonal treatment are recommended for intermediate- and high-risk prostate cancer (CaP). This study compared the long-term effects on health-related quality of life (HRQoL) of intermediate- and high-risk CaP patients managed with radiation therapy (RT) with vs. without hormone therapy (HT). Patients with intermediate- and high-risk CaP enrolled in the Center for Prostate Disease Research diagnosed from 2007 to 2017 were included. EPIC and SF-36 questionnaires were completed and HRQoL scores were compared for patients receiving RT vs. RT + HT at baseline (pretreatment), 6, 12, 24, 36, 48, and 60 months after CaP diagnosis. Longitudinal patterns of change in HRQoL were modeled using linear regression models, adjusting for baseline HRQoL, age at CaP diagnosis, race, comorbidities, National Comprehensive Cancer Network (NCCN) risk stratum, time to treatment, and follow-up time. Of 164 patients, 93 (56.7%) received RT alone and 71 (43.3%) received RT + HT. Both groups reported comparable baseline HRQoL. Patients receiving RT+HT were more likely to be NCCN high risk as compared to those receiving only RT. The RT + HT patients experienced worse sexual function, hormonal function, and hormonal bother than those who only received RT; however, HRQoL recovered over time for the RT + HT group. No significant differences were observed between groups in urinary and bowel domains or SF-36 mental and physical scores. Combined RT + HT treatment was associated with temporary lower scores in sexual and hormonal HRQoL compared with RT only. Intermediate- and high-risk CaP patients should be counseled about the possible declines in HRQoL associated with HT.

Long-term health-related quality-of-life outcomes in a racially diverse cohort of prostate cancer patients receiving retropubic versus robotic prostatectomy.

37 Background: This study compared 5-year health-related quality of life (HRQoL) outcomes among prostate cancer (PCa) patients who underwent a robotic-assisted radical prostatectomy (RARP) versus a radical retropubic prostatectomy (RRP), with a focus on race-specific outcomes for Caucasian American (CA) compared to African American (AA) men. RARPs have almost replaced RRPs in recent years, with few long-term studies focused on HRQoL and race. Methods: A prospective cohort study of HRQoL was conducted on patients diagnosed with PCa from 2007 to 2017 and enrolled in the Center for Prostate Disease Research (CPDR) Multicenter National Database. HRQoL was assessed with the EPIC instrument. Temporal changes in urinary and sexual-related quality of life domain scores were compared across surgery type (RARP versus RRP) at pre-treatment (“baseline”), 1-, 2-, 3-, 4-, and 5 years post-baseline. Longitudinal HRQoL patterns were modeled using generalized estimating equations (GEE), adjusting for baseline HRQoL and key clinical characteristics. Results: Of 497 PCa patients who met study inclusion criteria, 68% had RARP and 32% had RRP, with 22% AA men and 88% CA men. Baseline HRQoL domains were comparable across race and surgery type. In adjusted GEE analysis, no differences were noted between AA and CA patients. However, treatment-related differences were observed over time in urinary function (UF) and incontinence (UI) (p=0.02 and p=0.03, respectively), with lower HRQoL scores in RARP vs. RRP patients. Upon dual stratification by surgery type and race, the differences for UF and UI persisted (p=0.01 and p=0.03, respectively) with poorest outcomes observed, and similar trajectories of decline, for AA patients who received RARP. Conclusions: In this 10+ year prospective cohort study, AA patients receiving RARP had the poorest UF and UI outcomes which continued to decline for 5 years post treatment. In light of these findings, AA men considering RARP might benefit from discussions with their providers to set expectations regarding long-term urinary outcomes; though these decrements in HRQoL may be overshadowed by the minimally invasive nature of RARP.

PSA Doubling Time and Absolute PSA Predict Metastasis-free Survival in Men With Biochemically Recurrent Prostate Cancer After Radical Prostatectomy.

The aim of this study was to investigate the association of prostate-specific antigen (PSA) values on metastasis-free survival (MFS) in men with biochemically recurrent prostate cancer (BRPC) and PSA doubling time (PSADT)< 12 months. This datasetalso reflects an update with longer follow-up of our prior publications on the natural history of BRPC in the absence of treatment. In this report, we combined databases from the Center for Prostate Disease Research and Johns Hopkins University (CPDR/JHU). In the CPDR/JHU radical prostatectomy database (30,936 total patients), 656 men with BRPC (> 0.2 ng/mL) after prostatectomy and PSADT<12 months, who received no adjuvant/salvage androgen deprivation and/or radiation therapy, were prospectively followed until radiologic evidence of metastasis and are included in this analysis. Metastasis occurred in 250 of 656 patients with BRPC (median follow-up, 5 years). PSADT< 7.5 months and Gleason score were independent risk factors for distant metastasis in multivariable analysis. Risk of metastasis increased for PSADT 6.01 to 7.50, 4.51 to 6.0, 3.01 to 4.50, and≤ 3.0 months, after adjusting for Gleason score. A PSA value≥ 0.5 ng/mL significantly and independently increased risk of metastasis in patients with PSADT< 12 months (hazard ratio, 2.79; 95% confidence interval, 1.47-5.29; P= .001). In men with PSADT< 12 months, PSADT≤ 7.5 months, PSA≥ 0.5 ng/mL, and Gleason score are independent predictors of MFS on multivariable analysis.

Longitudinal prostate cancer outcomes in a racially diverse cohort of military heath care beneficiaries: 1990-2017.

e16581 Background: Prostate cancer (PCa) incidence and mortality disproportionately burden African American (AA) men compared to Caucasian American (CA) men. An interplay of biological, social, and health care factors is blamed for this disparity. However, a recent multi-center study of the Veterans Affairs population found no differences in cancer progression, disease specific survival, or overall survival for AA versus CA men. This study examines a large, racially diverse military health care beneficiary cohort, enrolled over 25+ years, to examine the roles of race and comorbidity on metastasis-free and overall survival. Methods: The Center for Prostate Disease Research (CPDR) multi-center national database was the source of study subjects. Eligible patients included all men who underwent radical prostatectomy (RP) as primary treatment for PCa between January 1, 1990 to December 31, 2017. Comprehensive demographic, clinical, treatment, and outcomes data were collected on all enrollees. Unadjusted Kaplan-Meier estimation curves and multivariable Cox proportional hazards analysis with adjustment for key clinical and pathologic factors were used to examine BCR-free, metastasis-free, and overall survival as a function of patient self-reported race (AA vs. CA). Results: There were 7,135 eligible men, among whom 22% self-reported as AA. Median age at RP and follow-up were 62 and 6.9 years, respectively. A total of 1521 BCR events, 210 metastasis events, and 879 deaths occurred. Compared to CA men, AA men were younger at diagnosis (59.4 vs. 62.7 years, p &lt; 0.05) with higher median PSA (5.8 vs. 5.5 ng/mL, p &lt; 0.05); however, NCCN risk strata, as well as clinical and pathologic stage and grade were distributed comparably across race. Despite slightly poorer BCR-free survival for AA men in both unadjusted and adjusted analysis, there were no statistically significant differences in 5-, 10-, and 15-year probabilities for metastasis-free or overall survival. Conclusions: In this racially diverse equal-access health care setting, this longitudinal cohort study revealed no differences in distant metastasis or overall survival between AA and CA men. Future work will examine molecular signatures of metastatic cancer.

27-year patterns in high-risk prostate cancer treatment in a racially diverse, equal-access health care setting.

e16583 Background: Despite the significant stage migration of prostate cancer (CaP), a large proportion of patients harbor high-risk disease. Few CaP series provide long term outcomes with the ability to assess disparities in diverse populations. We examined 27-year outcomes among men treated for high risk CaP in a large, racially diverse, equal access system. Methods: A retrospective cohort study was conducted of patients enrolled into the Center for Prostate Disease Research (CPDR) Multi-Center National Database from 1990-2017. There were 2,241 CaP patients who were NCCN-defined high risk, had a self-reported race of Caucasian (CA) or African American (AA), and had a primary treatment of hormonal therapy (HT), radical prostatectomy (RP), radiation therapy (RT) or no treatment (NoTX). Demographic and clinico-pathological variables were evaluated and stratified by race and treatment. Primary study outcomes included temporal patterns in race-specific treatment intensity and type(s). Secondary outcomes included biochemical recurrence (BCR)-free survival (BRFS) and distant metastasis-free survival (DMFS). Unadjusted Kaplan-Meier estimation curves and multivariable Cox proportional hazards analysis were used. Results: Mean patient age at CaP diagnosis and follow-up time were 68.1 years and 7.8 years, respectively. AAs made up 26.9% of the study cohort. Median prostate specific antigen level was 20.9 ng/mL (IQR: 7.8 - 35.0). 52% of patients had a biopsy Gleason score of 8 or greater. 714 (31.9%) underwent RP, 966 (43.1%) underwent RT, 288 (12.9%) received primary HT, and 273 (12.2%) had NoTX. A decreasing trend of HT, with stable rates of RP and RT, was observed. Median time to BCR after RP and RT was 1.3 and 3.1 years, respectively. After RP and RT, 51.2% and 39.3% experienced BCR while 10.9% and 12.7% experienced distant metastasis, respectively. There were no significant racial differences in treatment intensity, treatment type, BRFS or DMFS. Conclusions: In this longitudinal series, there was racial comparability for all study outcomes. Moreover, in this high-risk patient series with long-term follow up (median = 6.9 years), nearly 50% did not experience BCR, and only 1 in 10 men developed metastasis.

Abstract A005: Patterns in distant metastasis at diagnosis in a racially diverse, longitudinal cohort of prostate cancer patients: 1989-2013

Abstract Introduction: The introduction of PSA screening in the U.S. and its nationwide use as a prostate cancer (PCa) screening modality led to a spike in the incidence of localized PCa in the early 1990s. With this shift toward earlier stage disease at presentation, concerns were raised for overdetection and overtreatment of clinically insignificant PCa. In response to such concerns, professional guidelines on PSA screening practices have changed over time. In 2008 the US Preventive Services Task Force (USPSTF) gave PSA screening for detection of prostate cancer a Grade D recommendation for older men (&amp;gt;=75 years), and in 2012 this grade D was extended to men of all age. More recently, in 2017 a draft of revised guidelines was released, elevating the letter Grade to C, only for men aged 55-69 years. Yet three compelling studies have been published that reveal increases in the diagnosis of metastatic PCa (mPCa) in U.S. men, with provocative associations in time to changes in PSA screening guidelines, prompting concern that a stage shift toward more advanced PCa at diagnosis may be occurring. The primary aim of this study was to examine time trends in mPCa at time of diagnosis, over a 20+-year study period, in a racially diverse longitudinal cohort with equal access to health care. The primary hypotheses were that mPCa at diagnosis declined after the introduction of PSA screening and that such declines would be comparable in both Caucasian (CA) and African American (AA) patients in this cohort. Methodology: The Center for Prostate Disease Research (CPDR) Multi-Center National Database was the source of patients for this study. Men under suspicion for PCa and undergoing TRUS-guided biopsy for PCa detection are eligible for enrolment in this database. This study focused on those with biopsy-confirmed PCa between January 1, 1989 and December 31, 2013. Trends in mPCa at the time of diagnosis were examined for the overall cohort, as well as stratified by race (AA and CA) and patient age at CaP diagnosis (&amp;lt;75 years versus ≥75 years). Poisson regression with a log link function was used to estimate annual percent change (APC) in mPCa at diagnosis, as a proportion of all newly diagnosed PCa per year. Multivariable logistic regression was used to model predictors of mPCa at diagnosis as a function of PSA screening history and race. Results: A total of 462 men presented with mPCa and were eligible for inclusion. The decline in APC for the overall cohort was statistically significant (APC = -8.5%, p &amp;lt;0.0001). When APCs were computed for across race, both AA and CA patients were observed to have statistically significant negative change over time in APC (-10.1%, p&amp;lt;0.0001 and -8.7%, p &amp;lt;0.0001, respectively). However, there was no interaction between race and year of metastatic PCa diagnosis (p=0.49). When stratified by age group, patients aged ≥75 years had a smaller magnitude of decline in APC compared to those &amp;lt;75 years (-3.9%, p&amp;lt;0.0001 and -10.1%, p&amp;lt;0.0001, respectively). The interaction between age group and diagnosed year was significantly different (p=0.0011). In multivariable analysis, both the number of prior PSA screenings (OR ≥5 vs. None = 0.35, p &amp;lt;0.0001 = 0.35, p &amp;lt;0.0001) and race (OR for AA vs. CA=1.77, p&amp;lt;0.0001) strongly predicted mPCa. Conclusions: In this longitudinal, racially diverse cohort with equal health care access, significant declines in mPCa at diagnosis were observed over a 20+-year study period. This is contrast to other recent studies that have demonstrated increases in mPCa following changes in USPSTF guidelines. There was, however, a difference in the magnitude of decrease in oldest patients (≥75 years) compared to younger men, which may have been influenced by changing PSA screening recommendations in 2008 by the USPSTF. Continued attention to shifts in mPCa at diagnosis is needed to determine the impact of changes in screening recommendation. Citation Format: John McCauley, Huai-Ching Kuo, Inger L. Rosner, Yongmei Chen, Lauren Hurwitz, Sean Stroup, Joseph R. Sterbis, Christopher Porter, Timothy C. Brand, Shiv Srivastava, Jennifer Cullen. Patterns in distant metastasis at diagnosis in a racially diverse, longitudinal cohort of prostate cancer patients: 1989-2013 [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr A005.

Abstract 5765: Immunobiomarkers: Structural and functional characterization of single chain fragment variable (scFv) to ERG from a mouse monoclonal antibody

Abstract Introduction: Biomarkers for early detection, disease stratification as well as treatment strategies are a major area of focus in prostate cancer (CaP) research. The gene fusion involving ERG and the TMPRSS2 gene promoter contributes to expression of ERG in CaP, serving as a biomarker for CaP. This led to the development of monoclonal or polyclonal antibodies against ERG protein for diagnostic or therapeutic purposes. As the use of intact monoclonal antibody is limited due to large size and low cell penetration, we hypothesized that single chain fragment variable (scFv) and single domain antibody (sdAb) known as minibodies will be valuable as therapeutic agents targeting ERG protein. Towards this goal, the present study addresses the following: i) Characterization of variable heavy (VH) and variable light (VL) chain sequences and generation of expression vectors; ii) Assessing the specificity of binding of scFv and sdAb to ERG protein; iii) Functional evaluation of scFv and sdAb in cellsMethods: We generated VH and VL encoding sequences using RNA derived from hybridoma cells secreting anti-ERG monoclonal antibody designated 9FY. scFv-9FY and sdAb-9FY fragments represent scFv and sdAb , respectively were cloned in an eukaryotic and prokaryotic expression vectors. The proteins (scFv and sdAb) were analyzed by western blot and ELISA. The binding of scFv and sdAb to ERG protein in live cells was evaluated by bimolecular fluorescence complementation (BiFC) assay. Biological effects of scFv and sdAb were assessed in HEK293, VCaP and LNCaP cells. Results: Analysis was carried out to determine the primary DNA sequence of scFv fragments. Using the predicted amino acid sequence, we identified CDR1, CDR2 and CDR3 regions. scFv expressed in prokaryotic vector was purified and used for the evaluation of immunoreactivity to ERG by ELISA. The affinity of scFv and sdAb to ERG was demonstrated through their binding to ERG protein in HEK293 cells by using BiFC assay. This involved the generation of chimeric proteins in which scFv or sdAb coding sequences were fused in-frame to the Venus N- or C-terminal segment separated by a flexible linker of 10 amino acids. Minibodies scFv and sdAb, upon introduction into VCaP cells through transfection, showed cytotoxic effects similar to the observations noted with siRNA against ERG.Conclusions: Here we showed that scFv and sdAb minibodies exhibit high affinity for ERG protein. This property enables them to disrupt the functions mediated by ERG in cells. Given the prevalence of ERG overexpression in prostate cancer, the novel agents based on scFv and sdAb have the potential to interfere with the effect or functions of ERG and are likely to be beneficial in the treatment of CaP. Source of Funding: Center for Prostate Disease Research, USU Grant HU0001-10-2-0002, NCI/EDRN Grant ACN12011-001-0, and the NCI Grant R01CA162383. Citation Format: Shyh-Han Tan, Anshu Rastogi, Sreedatta Banerjee, Annie Bagga, Charles Xavier, Ahmed Mohamed, Denise Young, Gyorgy Petrovics, Albert Dobi, Isabell A. Sesterhenn, Jacob Kagan, Sudhir Srivastava, David G. David, Inger L. Rosner, Shiv Srivastava, Alagarsamy Srinivasan. Immunobiomarkers: Structural and functional characterization of single chain fragment variable (scFv) to ERG from a mouse monoclonal antibody [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5765.

Alkaline Phosphatase Kinetics Predict Metastasis among Prostate Cancer Patients Who Experience Relapse following Radical Prostatectomy.

Introduction Metastasis prostate cancer (CaP) occurs in a small fraction of patients. Improved prognostication of disease progression is a critical challenge. This study examined alkaline phosphatase velocity (APV) in predicting distant metastasis-free survival (DMFS). Materials and Methods This retrospective cohort study examined CaP patients enrolled in the Center for Prostate Disease Research (CPDR) multicenter national database who underwent RP and experienced BCR (n=1783). BCR was defined as a PSA ≥ 0.2 ng/mL at ≥ 8 weeks post-RP, followed by at least one confirmatory PSA ≥ 0.2 ng/mL or initiation of salvage therapy. APV was computed as the slope of the linear regression line of all alkaline phosphatase (AP) values after BCR and prior to distant metastasis. APV values in the uppermost quartile were defined as “rapid” and compared to the lower three quartiles combined (“slower”). Unadjusted Kaplan Meier (KM) estimation curves and multivariable Cox proportional hazards analysis were used to examine predictors of DMFS. Results Of the 1783 eligible patients who experienced post-RP BCR, 701 (39.3%) had necessary AP data for APV calculation. PSA doubling time (PSADT) and APV were strongly associated (p=0.008). No differences in APV were observed across race. In KM analysis, significantly poorer DMFS was observed among the rapid versus slower APV group (Log-rank p=0.003). In multivariable analysis, a rapid APV was predictive of a twofold increased probability of DMFS (HR = 2.2; 95% CI = 1.2, 3.9; p = 0.008), controlling for key study covariates. Conclusions Building on previous work, this study found that rapid APV was a strong predictor of DMFS for a broader group of CaP patients, those who undergo post-RP BCR who were enrolled in a longitudinal cohort with long-term follow-up and equal health care access. APV is worth considering as a complementary clinical factor for predicting DMFS.

PD20-05 RISK OF MEN WITH INTERMEDIATE RISK PROSTATE CANCER GOING ONTO DEFINITIVE TREATMENT DURING ACTIVE SURVEILLANCE; DOES A HIGH PSA PREDICT A WORSE OUTCOME?

You have accessJournal of UrologyProstate Cancer: Localized: Active Surveillance III1 Apr 2018PD20-05 RISK OF MEN WITH INTERMEDIATE RISK PROSTATE CANCER GOING ONTO DEFINITIVE TREATMENT DURING ACTIVE SURVEILLANCE; DOES A HIGH PSA PREDICT A WORSE OUTCOME? John Burns, Lauren Hurwitz, Katherine Levie, Fernando Caumont, Timothy Brand, Inger Rosner, Sean Stroup, Joseph Sterbis, Jennifer Cullen, and Christopher Porter John BurnsJohn Burns More articles by this author , Lauren HurwitzLauren Hurwitz More articles by this author , Katherine LevieKatherine Levie More articles by this author , Fernando CaumontFernando Caumont More articles by this author , Timothy BrandTimothy Brand More articles by this author , Inger RosnerInger Rosner More articles by this author , Sean StroupSean Stroup More articles by this author , Joseph SterbisJoseph Sterbis More articles by this author , Jennifer CullenJennifer Cullen More articles by this author , and Christopher PorterChristopher Porter More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1009AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Management of patients with intermediate risk (IR) prostate cancer (PCa) based on PSA elevation but with Gleason 3+3 disease remains elusive; some authors have suggested that many could be offered active surveillance (AS). This study evaluated time to definitive treatment (DT) for PCa patients with IR (defined by PSA alone), low risk (LR) and favorable intermediate-risk (FIR) patients. METHODS A retrospective cohort study was performed from the Center for Prostate Disease Research (CPDR) multi-center national database between 1989-2013. Men ≤75 y/o with ≤ cT2a, Gleason ≤ 3+4 PCa, and PSA < 20, were included. We stratified patients into LR (defined by NCCN criteria), FIR (defined as Gleason ≤ 3+4, PSA <10) and IR PCa (defined by NCCN LR criteria, except PSA 10-20). The study population was restricted to men on AS, defined as men who received no definitive treatments in the first 12 months following diagnosis. The primary outcome was progression to DT among patients on AS. Time to DT was compared between the three comparison groups using Kaplan-Meier survival curves and the log-rank test. RESULTS Of 4,244 eligible men, there were 3,005 LR, 337 IR, and 902 FIR patients. Management on AS in the CPDR cohort was 16.1%, 10.6%, and 7.9% for LR, IR, and FIR respectively. Age at diagnosis was similar: 64.1 for LR, 65.7 for IR, and 63.3 years for FIR. Over one-quarter of patients were African American. PSA at diagnosis was 4.4 for LR, 13.7 for IR, and 5.5 for FIR patients. Median time to DT was 20.0, 17.2, and 20.6 months, for each risk group respectively. In patients undergoing initial AS, 23.3% LR, 25% IR, 36.6% FIR went on to DT during follow up; importantly, there were no significant differences between groups (Fig 1), p = 0.08. CONCLUSIONS In this large racially diverse, prospectively collected DB, AS remains underutilized in patients with low risk and intermediate risk disease. Patients with PSA defined IR disease who undergo AS progress to DT at similar rates as LR and FIR patients, and should be considered candidates for AS. We recognize long term follow up is needed to evaluate cancer progression in this cohort. Current efforts are underway to monitor trends in AS in recent years, as overtreatment rates continue to decrease. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e403 Advertisement Copyright & Permissions© 2018MetricsAuthor Information John Burns More articles by this author Lauren Hurwitz More articles by this author Katherine Levie More articles by this author Fernando Caumont More articles by this author Timothy Brand More articles by this author Inger Rosner More articles by this author Sean Stroup More articles by this author Joseph Sterbis More articles by this author Jennifer Cullen More articles by this author Christopher Porter More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Abstract 2830: Secreted protein acidic and rich in cysteine antigen and autoantibodies in sera of prostate cancer patients: Potential use in diagnosis /prognosis

Abstract Objectives: Improvements in blood based biomarkers for detecting clinically significant prostate cancer (CaP) or for distinguishing between indolent and aggressive CaP are critical in enhancing the management of this most common non-skin cancer of men in the US. These biomarkers include tumor associated antigens (TAAs) and autoantibodies (AAbs) against TAAs in patient sera. SPARC/Osteonectin is highly expressed in metastatic cancers (glioblastoma, melanoma, breast cancer and prostate cancer) and promotes bone metastasis and epithelial-mesemchymal transition. Our comparative transcriptome analyses of well/moderately differentiated CaP with poorly differentiated CaP, defined SPARC as central node in the network of genes with common regulatory elements (NKXH_NKXH_HOX) associating with poorly differentiated CaP. Further, we reported associations of high levels of SPARC mRNA or protein with Gleason 8-10 or poorly differentiated primary tumors and association with metastatic progression. The aims of this study are: i) Quantify SPARC antigen in the sera CaP patients; ii) Are AAbs against SPARC present in the serum of CaP patients?; iii) Is there a correlation between SPARC AAb level in patient sera and disease status? iii) Does SPARC AAb level vary according to distinct ethnic groups? Methods: Sera from CaP patients and healthy controls were evaluated for SPARC antigen using a commercial enzyme-linked immunosorbent assay (ELISA) kit. AAbs against SPARC were determined by ELISA utilizing recombinant full-length human SPARC protein as a substrate. For evaluation we used Caucasian American (CA, n=117) and African American (AA, n=111) CaP patients comprising Gleason 6-10, and healthy controls (CA, n=52; AA, n=45). Results: SPARC antigen levels in the sera showed a difference in the overall case versus control groups (p=0.0016) and this trend was observed only in AA (p=0.0015) in comparison to CA patients (p=0.1709). SPARC AAbs were detected in the sera and the values were significant in the overall case versus control (p&amp;lt; .0001) and also in CA (p&amp;lt;.0001) and AA (p&amp;lt;.0001) CaP patients with levels significantly lower in patients compared to controls. AAb reactivity for CaP patients was similar between CA and AA groups. Conclusions: This study demonstrated the presence of AAbs against SPARC in CaP patient serum for the first time. Of note, highly significant differences were noted between CaP patient (low) and controls (high) sera, across different ethnic groups. These data suggest further evaluation of SPARC AAbs as a promising serum biomarker for CaP. Source of Funding: This research was supported by the Center for Prostate Disease Research, Uniformed Services University Grant HU0001-10-2-0002. Citation Format: Anshu Rastogi, Andy Martinez, Amina Ali, Shyh-Han Tan, Jennifer Cullen, Yongmei Chen, Gyorgy Petrovics, Albert Dobi, Lakshmi Ravindranath, Denise Young, Isabell Sesterhenn, Jacob Kagan, Sudhir Srivastava, David McLeod, Inger Rosner, Shiv Srivastava, Alagarsamy Srinivasan. Secreted protein acidic and rich in cysteine antigen and autoantibodies in sera of prostate cancer patients: Potential use in diagnosis /prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2830. doi:10.1158/1538-7445.AM2017-2830

Predictors of post-surgical race-specific prostate cancer progression.

5048 Background: Disparity in prostate cancer (CaP) incidence and mortality for African American (AA) versus Caucasian American (CA) men may reflect tumor biology, comorbidity, treatment, follow-up care, and/or health care access. In a racially diverse cohort of patients undergoing radical prostatectomy (RP), this study examined how race, comorbidity, and PSA doubling time (PSADT) impact CaP progression. Methods: Enrollees in the Center for Prostate Disease Research (CPDR) Multi-Center National Database from 1989-2014 who underwent RP within 12 months of CaP diagnosis were eligible. Biochemical recurrence (BCR) was defined as PSA ≥0.2 ng/mL post-RP. Comorbid conditions included coronary artery disease (CAD), cerebral vascular incident (CVI), Type II diabetes (DB), hypertension (HT), elevated cholesterol (EC), lung disease (COPD), prostatitis (PS), renal insufficiency (RI) and other cancer (OC). Multivariable Cox proportional hazards (PH) analysis was used to examine comorbid conditions (yes vs. no) and PSADT ( &lt; 3, 3-8.9, 9-14.9, and ≥15 mos) to predict BCR, controlling for age at RP, D’Amico risk stratum, pathology features, and adjuvant treatment. Results: A total of 6,785 patients were eligible; 22% AA and 78% CA. Median age and follow-up was 62 and 6.1 years, respectively. Across race, comparable median follow-up time, distributions of pathologic features and adjuvant treatments were observed. However, AA vs. CA patients had greater HT (53 vs. 39% p &lt; 0.0001), DB (17 vs. 7%, p &lt; 0.0001), and RI (3 vs. 1%, p = 0.002). Alternatively, CA vs. AA patients had greater CVD (10 vs. 7%, p = 0.0008) and OC (3 vs. 0.5%, p &lt; 0.0001). Cox PH analysis showed poorer BCR-free survival for AA vs. CA men (HR = 1.28, CI = 1.11, 1.48, p = 0.0009) adjusting for D’Amico risk stratum, pathology, and treatment. PSADT, not comorbidity, was a critical predictor of BCR, with poorest outcome at extremes: HR PSADT &lt; 3 vs. &gt; = 15 months = 41.5, CI = 33.6, 51.3, p &lt; 0.0001). Conclusions: Despite comparable health care access and distribution in clinical risk stratum and pathology features, race persisted in predicting poor CaP outcome. Disparate comorbidity for AA and CA men did not eliminate this difference. PSADT remained the most striking determinant of poor BCR-free survival.

PSA doubling time (PSADT) and proximal PSA value predict metastasis-free survival (MFS) in men with biochemically recurrent prostate cancer (BRPC) after radical prostatectomy (RP).

5075 Background: We previously reported a relationship between PSADT and MFS in BRPC post RP (Pound 1999; Freedland 2007; Antonarakis 2012). In men with PSADT&lt;12 months, who are at high risk of lethal PCa, we sought to identify a PSA cutpoint (proximal PSA; PP) that indicates the imminent emergence of metastasis (M+). In this report we combined Center for Prostate Disease Research and Johns Hopkins (CPDR/JHU) databases to investigate the association of the PP value on MFS in men with BRPC and PSADT &lt;12 mos. Methods: In the CPDR/JHU RP database (31,296), 513 men with BCR (&gt;0.2ng/ml) with PSADT &lt;12 mos who received no adjuvant/salvage ADT/RT were prospectively followed until radiological evidence of M+ are included in this analysis. All patients were evaluated yearly with &gt;1 PSA and scans at regular intervals until M+. Associations with MFS were compared using logrank test and Cox regression. The PP is the most recent value &gt;6 months prior to M+/censor. Results: M+ occurred in 218 of 513 patients with BRPC (median follow up 9 years). Risk of M+ increased successively for PSADT 6.0-7.5, 4.5-6, 3.0-4.5, and &lt;3.0 months, adjusted for pT stage and Gleason score. PP ≥10ng/ml significantly increased risk of M+ in pts with PSADT &lt;12 mos, regardless of PSADT subgroup, hazard ratio=2.95, p&lt;.0001. Median MFS was 4.0 years at PP &gt;10ng/ml vs 20 years at PP &lt;10ng/ml. Table 1 shows median MFS and 3, 5, and 7 year MFS rates in subgroups with PSADT &lt;3 and 3.01-6 months representing the highest risk groups. Conclusions: In men with PSADT&lt;12 months, PSADT subgroups &lt;7.5 months and PP &gt;10ng/ml are independent predictors of MFS, adjusted for pT stage and Gleason score. PP ≥10ng/ml further define risk of M+ in BRPC with PSADT&lt;12 months. These data can assist physicians in patient counseling and clinical trial design. [Table: see text]

MP14-18 ALKALINE PHOSPHATASE VELOCITY PREDICTS METASTASIS AMONG PROSTATE CANCER PATIENTS WHO EXPERIENCE BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History II1 Apr 2017MP14-18 ALKALINE PHOSPHATASE VELOCITY PREDICTS METASTASIS AMONG PROSTATE CANCER PATIENTS WHO EXPERIENCE BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY Carolyn Salter, Jennifer Cullen, Inger Rosner, Huai-Ching (Claire) Kuo, and Adam Metwalli Carolyn SalterCarolyn Salter More articles by this author , Jennifer CullenJennifer Cullen More articles by this author , Inger RosnerInger Rosner More articles by this author , Huai-Ching (Claire) KuoHuai-Ching (Claire) Kuo More articles by this author , and Adam MetwalliAdam Metwalli More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.482AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Most patients undergoing radical prostatectomy (RP) for treatment of prostate cancer (CaP) will not develop biochemical recurrence (BCR) or distant metastasis (dMET). Risk factors have been difficult to establish and the role of neo-adjuvant, adjuvant, and/or salvage therapy in preventing or delaying these events is not well understood. This study builds on previous work examining alkaline phosphatase velocity (APV) in predicting dMET for castrate-resistant CaP (CRPC) patients, in a large, racially diverse cohort of patients treated in an equal access military health care system. METHODS This retrospective cohort study examined CaP patients enrolled in the Center for Prostate Disease Research (CPDR) multi-center national database who underwent RP and subsequently experienced BCR (n=1725). BCR was defined as a PSA ≥ 0.2 ng/mL at ≥ 8 weeks post-RP, followed by a confirmatory PSA ≥ 0.2 ng/mL. APV was computed as the slope of the linear regression line of all alkaline phosphatase (AP) values after RP and prior to dMETs. APV values in the uppermost quartile were defined as ″rapid″ and compared to those in the lower 3 quartiles combined. Salvage therapies were categorized as: hormone therapy only, external radiation therapy only, or multi-treatment. Unadjusted Kaplan Meier curves and multivariable Cox Proportional Hazards analysis were used to model time to dMET. RESULTS Of the 1725 eligible patients, 736 (42.7%) had sufficient data to calculate APV. Those without APV data had a greater proportion of dMET and a faster time to dMET, as well as poorer pathologic features than those who had sufficient APV data. dMET was observed in 11% of patients. We observed a significantly faster time to dMET among the rapid APV group (p<0.001). In multivariable analysis, rapid APV was predictive of over a two-fold increased odds in dMET (HOR = 2.08, p = 0.0215). CONCLUSIONS In CaP patients with BCR after RP, rapid APV is a useful predictor of dMET over time. Salvage therapy did not appear to predict dMET. This study builds on previous work demonstrating APV as predictive of dMET among castrate resistant CaP (CRPC) patients. APV may be a valuable tool for prognosticating dMET in a broader patient group, at a time point upstream of CRPC, namely CaP patients who experience BCR after RP. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e168-e169 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Carolyn Salter More articles by this author Jennifer Cullen More articles by this author Inger Rosner More articles by this author Huai-Ching (Claire) Kuo More articles by this author Adam Metwalli More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...