Prostate Cancer In Population Research Articles

Real-world cardiovascular outcomes with novel anti-androgen agents in prostate cancer patients.

e16510 Background: Abiraterone use is associated with significant cardiovascular (CV) morbidity in clinical trials, but the magnitude of this morbidity in contemporary US prostate cancer (PC) population remains unknown. We examined a large medical claims database to answer this important question. Methods: We retrospectively reviewed Marketscan claims database (1/1/2013 to 9/30/2015) to identify adults with diagnosis of localized PC, recurrent localized PC, biochemically recurrent non-metastatic PC and metastatic PC who received treatment with androgen deprivation therapy (ADT) alone or ADT with novel antiandrogen agents (abiraterone or enzalutamide). The primary outcome measure was composite severe CV outcome of acute myocardial infarction (MI), stroke or heart failure (HF). We used Cox regression model with time dependent covariates to estimate the CV risk of various therapies. Results: A total of 7030 patients of PC were identified- 1285 received ADT for localized PC, 424 received ADT for recurrent localized PC, 554 received ADT for biochemically recurrent non-metastatic PC, 256 received ADT alone for metastatic PC and 1366 received abiraterone or enzalutamide with ADT for metastatic PC. During the study period, 143 severe CV events occurred, resulting in an incidence rate of 0.74 per 100 patient-years. In multivariate analysis, abiraterone use was associated with a trend towards increased risk of severe CV compared to non-abiraterone users (HR = 1.58; 95% CI: 0.98-2.59, p= 0.06). No such increased risk was detected for ADT (HR = 1.35; 95% CI: 0.92-2.00, p= 0.12) or enzalutamide (HR = 0.84 95% CI: 0.34-2.11, p= 0.71). Conclusions: To our knowledge, this is the first study to present real-world data on CV outcomes of PC patients receiving novel anti-androgens. Our findings support the trend towards increased severe CV risk seen in abiraterone trials. No such association was seen for enzalutamide. Additional analyses with a longer follow-up duration are planned.

The Long-Term Dynamics of the Incidence of Prostate Cancer in the Omsk Region

The purpose of this study is to assess the dynamics of the incidence of prostate cancer in the Omsk region for the period 2006– 2017. Materials and methods. A retrospective epidemiological analysis of data from statistical reports (Form No. 7) of the Omsk Oblast health authorities for the period 2006–2017 was carried out. Results and its discussion. In the structure of oncological morbidity in the male population of the Omsk Region, the proportion of prostate cancer was 16.3% and was lower than the average Russian average (17%). In rural areas, compared with the regional center, higher rates of increase in the incidence of prostate cancer were observed (by 1.2 times). In general, the situation on the territory of the Omsk Region is similar to the global trend, characterized by an increase in the incidence of the male population of prostate cancer, which is a reflection of insufficient attention to primary cancer prevention, features of the socio-economic situation in the Russian Federation. Findings. 1. In the long-term dynamics of incidence of prostate cancer in the region for the period 2006–2017. there was a moderately pronounced upward trend in indicators (Tpr. = 3.94%; p < 0.05), with higher growth rates (1.2 times) in rural areas compared to the regional center (respectively, 3.56% and 3.04%; p < 0.001). 2. From 2006 to 2017 incidence of prostate cancer in the Omsk region increased 2.3 times in total (from 29.2 to 66.2 per 100 ths) and 1.8 times in standardized indicators (from 24.8 to 44.4 per 100 ths). 3. Despite the obvious relevance of the pathology, the prevalence of known risk factors for the development of prostate cancer in the Omsk Region has not been studied sufficiently, which requires scientific justification and improvement of approaches to primary prevention with regard to regional characteristics.

Targeting DNA Repair Defects for Precision Medicine in Prostate Cancer.

Genomic studies of localized and metastatic prostate cancer have identified a high prevalence of clinically actionable alterations including mutations in DNA repair genes. In this manuscript, we review the current knowledge on DNA repair defects in prostate cancer and provide an overview of how these alterations can be targeted towards a personalized prostate cancer management. Twenty to 25% of metastatic prostate cancers harbor defects in DNA repair genes, most commonly in the homologous recombination genes. These defects confer increased sensitivity to platinum chemotherapy or poly (ADP-ribose) polymerase (PARP) inhibitors. Recent trials also support a synergistic effect of combining these therapies with androgen receptor-targeting agents. Identification of mismatch-repair defects could result in defining a prostate cancer population who may benefit from immune checkpoint inhibitors. These data have implications for family testing and early diagnosis, as many of these mutations are linked to inherited risk of prostate cancer. The DNA damage repair pathways are clinically relevant in prostate cancer, being a target for precision medicine; combination with standard-of-care androgen receptor (AR)-targeting agents may be synergistic.

The synthetic retinoid ST1926 attenuates prostate cancer growth and potentially targets prostate cancer stem-like cells.

Retinoids are vitamin A derivatives that regulate crucial biological processes such as cellular proliferation, apoptosis, and differentiation. The use of natural retinoids in cancer therapy is limited due to their toxicity and the acquired resistance by cancer cells. Therefore, synthetic retinoids were developed, such as the atypical adamantyl retinoid ST1926 that provides enhanced bioavailability and reduced toxicity. We have assessed the in vitro and in vivo antitumor properties and mechanism of action of ST1926 in targeting cancer stem-like cells population of human prostate cancer (PCa) cell lines, DU145 and PC3, and mouse PCa cell lines, PLum-AD and PLum-AI. We demonstrated that ST1926 substantially reduced proliferation of PCa cells and induced cell cycle arrest, p53-independent apoptosis, and early DNA damage. It also decreased migration and invasion of PCa cells and significantly reduced prostate spheres formation ability in vitro denoting sufficient eradication of the self-renewal ability of the highly androgen-resistant cancer stem cells. Importantly, ST1926 potently inhibited PCa tumor growth and progression in vivo. Our results highlight the potential of ST1926 in PCa therapy and warrant its clinical development.

HSR19-109: The Healthy Days Measure in a Metastatic Castration-Resistant Prostate Cancer Population Treated With Novel Oral Therapies

Background: Health-related quality of life (HRQoL) is an important patient-reported outcome to assess in patients with prostate cancer (PC). A variety of general and disease-specific measures have been developed, but there is a lack of evidence on performance of the Centers for Disease Control and Prevention (CDC) Healthy Days (HDs) measure in a population with metastatic disease relative to other validated scales. Objective: To report and understand general HRQoL using the HDs instrument in patients with metastatic PC taking novel oral therapies and compare results to validated scales. Methods: Patients currently enrolled in a Medicare Advantage or Prescription Drug plan treated with enzalutamide or abiraterone acetate were eligible for inclusion. Patients undertook a telephone-based survey including 2 HRQoL questionnaires (Short-Form 36, version 2 [SF-36] survey and the CDC HDs measures), the Service Satisfaction with Cancer Care (SCA) instrument, and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue). Higher scores indicated higher HRQoL on all surveys, except the HDs scale, where higher numbers indicated lower HRQoL (ie, unhealthy days). Pearson correlations with SF-36 and HDs measures and SCA and FACIT-Fatigue were assessed. Results: 1,745 patients were eligible to participate; 269 completed the survey and were included in the analysis. The mean (standard deviation) age was 74.4 (±7.3) years and 82% were Caucasian. Patients had lower physical HRQoL and a higher number of physically unhealthy days, compared to mental health impacts on both scales. The mean Physical Component Summary (PCS) and Mental Component Summary (MCS) norm-based scores for the SF-36 were 39.9 (±10.6) and 53.4 (±10.4). The mean number of physically and mentally unhealthy days reported in a 30-day period were 9.2 (±11.3) and 3.9 (±7.7), respectively. The unadjusted correlations between scores were all statistically significant (P<.05). Conclusions: The SF-36 and HDs measures both indicated physical health was impacted more than mental health in these patients. The correlations with both HRQoL measures and the other scales were similar in terms of magnitude and significance. This indicates that the HDs instrument may be a useful measure for assessment of general HRQoL in patients with metastatic PC and provides an understanding of general HRQoL in this population that can be utilized to identify opportunities for enhancing patient-centered care.

Temporary Health Impact of Prostate MRI and Transrectal Prostate Biopsy in Active Surveillance Prostate Cancer Patients

PurposeTo assess the temporary health impact of prostate multiparametric MRI (mpMRI) and transrectal prostate biopsy in an active surveillance prostate cancer population. MethodsA two-arm institutional review board–approved HIPAA-compliant prospective observational patient-reported outcomes study was performed from November 2017 to July 2018. Inclusion criteria were men with Gleason 6 prostate cancer in active surveillance undergoing either prostate mpMRI or transrectal prostate biopsy. A survey instrument was constructed using validated metrics in consultation with the local patient- and family-centered care organization. Study subjects were recruited at the time of diagnostic testing and completed the instrument by phone 24 to 72 hours after testing. The primary outcome measure was summary testing-related quality of life (summary utility score), derived from the testing morbidities index (TMI) (scale: 0 = death and 1 = perfect health). TMI is stratified into seven domains, with each domain scored from 1 (no health impact) to 5 (extreme health impact). Testing-related quality-of-life measures in the two cohorts were compared with Mann-Whitney U test. ResultsIn all, 122 subjects were recruited, and 90% (110 of 122 [MRI 55 of 60, biopsy 55 of 62]) successfully completed the survey instrument. The temporary quality-of-life impact of transrectal biopsy was significantly greater than that of prostate mpMRI (0.82, 95% confidence interval [CI] 0.79-0.85, versus 0.95, 95% CI 0.94-0.97; P < .001). The largest mean domain-level difference was for intraprocedural pain (transrectal biopsy 2.6, 95% CI 2.4-2.8, versus mpMRI 1.3, 95% CI 1.1-1.5; P < .001). ConclusionTransrectal prostate biopsy has greater temporary health impact (lower testing-related quality-of-life measure) than prostate mpMRI.

Validation of the Decipher Test for Predicting Distant Metastatic Recurrence in Men with High-risk Nonmetastatic Prostate Cancer 10 Years After Surgery

BackgroundDecipher is a genomic classifier designed to predict the development of distant metastases after surgical treatment of prostate cancer (PC). Its long-term prognostic role in a high-risk PC population has not been investigated previously. ObjectiveTo determine the prognostic role of the Decipher genomic classifier in two high-risk PC case-control studies. Design, setting, and participantsPatients who developed distant metastases after surgery for high-risk, nonmetastatic PC in a European tertiary referral center from 1991 to 2011 were matched to patients not developing distant metastases (n=54). A validation study (n=298) was performed using a similar US case-control cohort. Formalin-fixed, paraffin-embedded tissue blocks from the index PC lesion were used for RNA extraction and gene expression analysis. Outcome measurements and statistical analysisThe outcome investigated was the development of distant metastasis within 10-yr follow-up. Multivariable logistic regression analysis was performed, with statistical significance considered at p<0.05. Results and limitationsIn both the European and US case-control studies, the median Decipher scores were higher in the population that developed metastases. In the multivariable analysis, each 10% increase in Decipher score translated to an increase in the risk of distant metastases within 10-yr follow-up, with an odds ratio of 1.53 (95% confidence interval [CI] 1.06–2.22; p=0.025) and 1.58 (95% CI 1.31–1.92; p<0.001) for the European and US cohorts, respectively. Median follow-up for the European cohort was 12yr (interquartile range 8–12). The study limitation is the small size of the European cohort. ConclusionsOur study validates Decipher as a predictor for metastatic recurrence even in patients with high-risk, nonmetastatic PC within 10-yr follow-up. Patient summaryDecipher is a test based on gene expression profiles in primary tumors in prostate cancer. It has already been proven to predict cancer recurrence after surgery, but this has not yet been shown for patients with high-risk prostate cancer. This is the first study confirming that Decipher predicts a patient's risk of developing cancer recurrence after surgery for high-risk prostate cancer.

Multiparametric magnetic resonance imaging-transrectal ultrasound fusion biopsies increase the rate of cancer detection in populations with a low incidence of prostate cancer.

PurposeTo prospectively evaluate the diagnostic yield of multiparametric magnetic resonance imaging (mpMRI)-fusion, transrectal ultrasound (TRUS)-guided prostate biopsies for detection of prostate cancer in an Asian population with a low incidence of prostate cancer.Materials and MethodsA total of 131 males with suspected prostate cancer were recruited to undergo fusion biopsy with the Artemis prostate fusion biopsy device (Eigen, Grass Valley, CA, USA). All patients underwent standard 12-core systematic biopsies in addition to biopsies targeted at the mpMRI-identified abnormal regions. Yield from the standard cores was compared with that from the targeted cores. Gleason scores of 4+3 or higher were considered significant.ResultsThe mean age of the patients was 63.54±7.96 years and the mean prostate-specific antigen value was 9.75±5.35 ng/mL. A total of 36 patients had cancer, of which 3 (8.3%) were detected only on standard cores and 3 (8.3%) only on targeted cores. Of the clinically significant cancers (n=30), targeted biopsy detected a higher number (28/30, 93.3%) than standard biopsy (21/30, 70.0%). A total of 6 of 8 cancers (75.0%) that were insignificant on standard biopsy were upgraded to significant cancer on targeted cores.ConclusionsEight percent of cancers were detected only on MRI-TRUS fusion-targeted biopsies, whereas the method upgraded more than two-thirds of insignificant cancers to significant cancers. Fusion biopsies thus provide incremental information over standard TRUS biopsies in the diagnosis of significant prostate cancer in populations with a low incidence of prostate cancer.

FAM84B promotes prostate tumorigenesis through a network alteration

Background:The aim of this study was to investigate the contributions of FAM84B in prostate tumorigenesis and progression.Methods:A FAM84B mutant with deletion of its HRASLS domain (ΔHRASLS) was constructed. DU145 prostate cancer (PC) cells stably expressing an empty vector (EV), FAM84B, or FAM84B (ΔHRASLS) were produced. These lines were examined for proliferation, invasion, and growth in soft agar in vitro. DU145 EV and FAM84B cells were investigated for tumor growth and lung metastasis in NOD/SCID mice. The transcriptome of DU145 EV xenografts (n = 2) and DU145 FAM84B tumors (n = 2) was determined using RNA sequencing, and analyzed for pathway alterations. The FAM84B-affected network was evaluated for an association with PC recurrence.Results:FAM84B but not FAM84B (ΔHRASLS) increased DU145 cell invasion and growth in soft agar. Co-immunoprecipitation and co-localization analyses revealed an interaction between FAM84B and FAM84B (ΔHRASLS), suggesting an intramolecular association among FAM84B molecules. FAM84B significantly enhanced DU145 cell-derived xenografts and lung metastasis. In comparison with DU145 EV cell-produced tumors, those generated by DU145 FAM84B cells showed a large number of differentially expressed genes (DEGs; n = 4976). A total of 51 pathways were enriched in these DEGs, which function in the Golgi-to-endoplasmic reticulum processes, cell cycle checkpoints, mitochondrial events, and protein translation. A novel 27-gene signature (SigFAM) was derived from these DEGs; SigFAM robustly stratifies PC recurrence in two large PC populations (n = 490, p = 0; n = 140, p = 4e−11), and remains an independent risk factor of PC recurrence after adjusting for age at diagnosis, Gleason scores, surgical margin, and tumor stages.Conclusions:FAM84B promotes prostate tumorigenesis through a complex network that predicts PC recurrence.

Downregulation of IQGAP2 Correlates with Prostate Cancer Recurrence and Metastasis

IQGAP2 was recently reported as a tumor suppressor of prostate cancer (PC). Nonetheless, its clinical implications remain unknown. To address this issue, we extracted data related to IQGAP2 mRNA expression and genomic alterations from multiple large datasets within the Oncomine and cBioPortal databases and performed in silico analyses to determine a potential association of IQGAP2 mRNA expression and its genomic alterations with PC progression. In 4 cohorts consisting of 118 normal prostate tissues and 277 PCs, IQGAP2 mRNA expression was significantly elevated particularly in low-grade (primary Gleason score ≤3) PCs; these changes separate PC from normal tissues with area under curve values of 0.7-0.8. Significant reductions in IQGAP2 mRNA levels and gene copy number occurred in more than 70 metastases compared to at least 230 local PCs. This duo-alteration in IQGAP2 expression supports IQGAP2 elevation suppressing and its downregulation facilitating PC progression. Deletion and missense mutations were detected in 23 of 492 primary PCs; these alterations significantly associate with PC recurrence (HR=2.71; 95% CI: 1.35-5.44; P=.005) after adjusting for known risk factors and correlate with reductions in disease-free survival (DFS, P=.002). IQGAP2 (5q13.3) genomic alterations were observed in SPOP-marked PCs and co-occurred with deletion in the RN7SK (16p12.2), SNORA50A (16q21), and SNORA50C (17q23.3) genes; the co-occurrence associated with reductions in DFS (P=4.14e-4). In two independent PC populations, MSKCC (n=130) and TCGA provisional (n=490), reductions in IQGAP2 mRNA expression were significantly associated with DFS. Collectively, this investigation reveals an association of IQGAP2 with PC progression.

Prostate cancer navigation: initial experience and association with time to care.

To evaluate factors associated with use of patient navigation in a prostate cancer population and identify whether navigation is associated with prolongedtime to care. Cancer patient navigation has been shown to improve access to cancer screening, diagnosis, and treatment, but little is known about patient navigation in prostate cancer care. All men diagnosed with localized prostate cancer between 2009 and 2015 were abstracted from the MaineHealthmulti-specialty tumor registry. Regression analyses controlling for patient-, disease-, and system-level factors evaluated characteristics associated with navigation utilization. The association between navigation utilization, barriers to care, and longer time to treatment was assessed with Cox proportional hazards regression. Of the patient population (n = 1587), 85% of men were navigated. Navigation use was associated with earlier year of diagnosis, treatment by a high-volume urologist, and lower risk disease (p < 0.05). Treatment delay was associated with low-risk disease (vs: intermediate OR 0.62, 95% CI 0.46-0.85 and high OR 0.16, 95% CI 0.1-0.25) and receipt of navigation services (OR 1.65, 95% CI 1.12-2.45) but not distance to care, insurance, or treatment choice. We observed that patients with low-risk prostate cancer were more likely to utilize navigation, but traditional barriers to care were not associated with utilization. Navigation was associated with longer time to treatment, which likely reflects clinically appropriate delays associated with greater shared decision making. Time to treatment may not be the ideal metric for evaluating navigation in prostate cancer; shared decision making, patient satisfaction, and psychosocial outcomes may be more appropriate.

Correlation of Androgen Deprivation Therapy with Cognitive Dysfunction in Patients with Prostate Cancer: A Nationwide Population-Based Study Using the National Health Insurance Service Database.

PurposeThe purpose of this study was to evaluate the association of androgen deprivation therapy (ADT) with cognitive dysfunction.Materials and MethodsUsing the National Health Insurance Service database of the entire Korean adult prostate cancer population (n=236,391), data on ADT and cognitive dysfunction between 2008 and 2015 were analyzed. We excluded patients previously diagnosed with cognitive dysfunction, dementia, or a cerebral event history. We tested the effect of ADT on the risk of cognitive dysfunction using propensity score–matched Cox proportional hazards regression models and Kaplan-Meier survival analysis. Our final cohort comprised of 35,401 individuals with prostate cancer, including 24,567 men (70.6%) who underwent ADT.ResultsDuring a mean follow-up period of 4.1 years, 4,741 patients were newly diagnosed with cognitive dysfunction. A statistically significant association was found between ADT and the risk of cognitive dysfunction (hazard ratio, 1.169; p=0.002). Meanwhile, age (≥ 70 years), diabetes, hypertension, cardiovascular history, and peripheral vascular disease were identified as factors that contribute to the increased risk of cognitive dysfunction. In contrast, the use of statins and aspirin was associated with a lower risk of cognitive dysfunction. Kaplan-Meier analysis demonstrated that patients aged 70 years or older who underwent ADT had the lowest cumulative probability of remaining cognitive dysfunction-free (log-rank p < 0.001).ConclusionOur results revealed an association between the use of ADT for the treatment of prostate cancer and an increased risk of cognitive dysfunction in a nationwide population-based study. This finding should be further evaluated in prospective studies.

Development of a Community Wellness Program for Prostate Cancer Survivors

ABSTRACT Men living with prostate cancer benefit from multidisciplinary wellness programs that include physical activity, nutrition, and stress reduction. Such programs have been shown to decrease treatment-related side effects and reduce the risk of cancer recurrence and other comorbidities associated with prostate cancer, while also improving overall fitness, health, and quality of life. Despite these benefits, access to wellness programs and educational resources for men with prostate cancer are limited in Canada. This study aimed to describe the development of the TrueNTH Lifestyle Management program, an initiative aimed at establishing evidence-based wellness programs in the community to improve access to trained professionals and educational resources specific to the prostate cancer population. Protocol for an integrated, community-based 12-wk intervention of group exercise, yoga, and nutrition education sessions was developed based on evidence and insights from existing cancer-specific programs. Evidence-based tools, resources, and training were developed to support program facilitation and standardize intervention delivery. Pilot testing using the RE-AIM framework was conducted at three distinct community-based sites with demographics, physical fitness, and quality-of-life outcomes collected at baseline and 12 wk. Fifty-eight participants enrolled, with 32 completing quality-of-life measures and 39 completing fitness measures before and after the 12-wk intervention. Significant improvements were seen in the physical measures of body composition, flexibility, dynamic balance, muscular endurance, and functional aerobic endurance as well as weekly moderate and strenuous physical activity levels (all P’s &lt; 0.05). TrueNTH Lifestyle Management provides evidence-based professional training and survivorship resources necessary for the potential implementation of a safe, effective, and beneficial community wellness program for men living with prostate cancer.

Biphasic Alteration of Butyrylcholinesterase (BChE) During Prostate Cancer Development

Butyrylcholinesterase (BChE) is a plasma enzyme that hydrolyzes ghrelin and bioactive esters, suggesting a role in modulating metabolism. Serum BChE is reduced in cancer patients. In prostate cancer (PC), the down-regulation is associated with disease recurrence. Nonetheless, how BChE is expressed in PC and its impact on PC remain unclear. We report here the biphasic changes of BChE expression in PC. In vitro, BChE expression was decreased in more tumorigenic PC stem-like cells (PCSLCs), DU145, and PC3 cells compared to less tumorigenic non-stem PCs and LNCaP cells. On the other hand, BChE was expressed at a higher level in LNCaP cells than immortalized but non-tumorigenic prostate epithelial BPH-1 cells. In vivo, BChE expression was up-regulated in DU145 xenografts compared to LNCaP xenografts; DU145 cell-derived lung metastases displayed comparable levels of BChE as subcutaneous tumors. Furthermore, LNCaP xenografts produced in castrated mice exhibited a significant increase of BChE expression compared to xenografts generated in intact mice. In patients, BChE expression was down-regulated in PCs (n = 340) compared to prostate tissues (n = 86). In two independent PC populations MSKCC (n = 130) and TCGA Provisional (n = 490), BChE mRNA levels were reduced from World Health Organization grade group 1 (WHOGG 1) PCs to WHOGG 3 PCs, followed by a significant increase in WHOGG 5 PCs. The up-regulation was associated with a reduction in disease-free survival (P = .008). Collectively, we demonstrated for the first time a biphasic alteration of BChE, its down-regulation at early stage of PC and its up-regulation at advanced PC.

Treatment in the STAMPEDE era for castrate resistant prostate cancer in the UK: ongoing challenges and underappreciated clinical problems

BackgroundThis study aimed to explore the opinions of healthcare professionals regarding the management of men with advanced prostate cancer with particular emphasis on treatment timing and sequencing; treatment adverse-effects and exercise a supportive therapy.MethodsSemi-structured interviews with a purposively selected group of healthcare professionals involved in prostate cancer care within the NHS, conducted over the phone or face to face. A total of 37 healthcare professionals participated in the interviews including urologists, clinical oncologists, medical oncologists, clinical nurse specialists, general practitioners, physiotherapists, exercise specialists, service managers, clinical commissioners and primary care physicians.ResultsThe availability of newer treatments for advanced prostate cancer as well as results from the STAMPEDE and CHAARTED trials has resulted in new challenges for patients and HCPs. This includes the impact of an increased workload on oncologists, a potential lack of clinical continuity between urology and oncology and uncertainties regarding optimal selection, timing and sequencing of chemotherapy and second-line treatment. Fitness for treatment in advanced prostate cancer populations remains a significant barrier to accessing therapies for patients with a poor performance status. Among this, muscle wastage can significantly affect performance status and consequentially compromise cancer therapy. Exercise was regarded as a potential therapy to mitigate the adverse-effects of treatment including the prevention or reduction in muscle wastage.ConclusionsThere is a lack of data guiding clinicians in this post STAMPEDE and CHAARTED era, work is needed to reassess and optimize the prostate cancer care pathway as it evolves. Exercise should be explored as a therapeutic option to mitigate the effects of long term ADT. Further study from a wider cohort of both prostate cancer care specialists and patients will aid in establishing a highly functioning pathway with optimal individualised care.Trial registrationSustained exercise TrAining for Men wIth prostate caNcer on Androgen deprivation: the STAMINA programme (RP-DG-1213-10,010). REC Reference: 15/SW/0260 IRAS Project ID: 178340 Hospital ID: STH 18391 approved on 24/08/2015.

2020 The clinical implications of a positive prostate cancer screen in patients undergoing a cardiac transplant evaluation

OBJECTIVES/SPECIFIC AIMS: Screening the general population for prostate cancer with prostate specific antigen (PSA) continues to be controversial. Patients with advanced heart failure undergoing evaluation for suitability for cardiac transplantation are often requested to undergo prostate cancer screening, with guiding evidence generated from the general population. The objective of this study is to determine the clinical implications of a positive prostate cancer screen result in this patient population. METHODS/STUDY POPULATION: A retrospective cohort study was performed on all men that were referred to a tertiary care cardiac transplant center between January 2000 and December 2015. Patients were classified as having either a “positive screen” (PSA≥4 ng/mL) or a “negative screen” (PSA&lt;4 ng/mL) at the point of evaluation. The primary outcome of time to listing for cardiac transplant (days) was calculated from the date of referral to the date of listing. A multivariable Cox proportional hazards model was developed to assess the association between a positive prostate cancer test result and listing for cardiac transplantation. RESULTS/ANTICIPATED RESULTS: Among the 704 patients included in this study, 66 men (9.4%) had a positive prostate cancer screen result. Men with a positive prostate cancer screen were approximately 4 year older (mean 58.5 vs. 54.1 years), more likely to have a diagnosis of Ischemic Cardiomyopathy (74% vs. 53%) and require continuous mechanical support (61% vs. 16%) at the point of transplant evaluation. The median time for listing for cardiac transplant was greater in patients with a positive PSA (119 vs. 48 days, p&lt;0.05). After adjusting for age, renal function, clinical status at evaluation, history of COPD, and year of referral, patients with a positive prostate cancer screen had a reduced hazards ratio (HR) for progressing to cardiac transplant listing compared with those with a negative screen (HR 0.58, 95%CI: 0.38–0.91). DISCUSSION/SIGNIFICANCE OF IMPACT: Screening patients undergoing cardiac transplant evaluation for prostate cancer with PSA has a low diagnostic yield. An individual’s PSA value is influenced by their age and clinical status at the time of screening, with a positive screen being associated with a reduced likelihood for progressing to listing for cardiac transplant.

PRM89 - Review of Frequently Implemented Patient Reported Outcomes in Current Prostate Cancer Clinical Trials

It is currently estimated that worldwide, prostate cancer will affect around 1 in 7 men during their lifetime. After lung cancer, it is the second highest cause of cancer deaths in men. This presents a widespread need for effective treatments. Patient reported outcomes (PROs) data provide useful insights into the symptoms and impacts experienced by patients, which can add supporting value to clinical trial endpoints when evaluating interventions. A number of PRO measures have been designed specifically for prostate cancer populations. This study provides a brief evaluation of the PROs most commonly used in current prostate cancer clinical trials. Clinicaltrials.gov was used to identify prostate cancer trials that include PROs as primary, secondary or exploratory endpoints. Search criteria were set to ensure that only interventional trials, currently recruiting and without results were included. From the search, 188 trials were identified. These included both generic and prostate cancer specific PROs. The five most common PROs were reviewed in accordance with regulatory guidelines. These were; the EPIC (n=38), the EORTC QLQ-C30 (n=31), the FACT-P (n=26), the IPSS (n=16) and the EORTC QLQ PR-25 (n=9). A review of these identified key features regarding their use. For example, although the EPIC is the most frequently used PRO, the recall period of four weeks may not always be appropriate depending on illness progression. Furthermore, the IPSS is just eight-items long, this can be beneficial as it reduces patient burden and thus increases compliance. However, it is important to evaluate whether this brief measure has sufficient conceptual coverage to assess total patient experience. Several validated measures exist in prostate cancer populations. Comparisons have been made between those most commonly used; their benefits and drawbacks have been summarized in this study. These findings should be considered when selecting an appropriate PRO to include in clinical trials.

MP51-10 PROSTATE CANCER NAVIGATION AND TIME TO TREATMENT

You have accessJournal of UrologyGeneral & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life & Shared Decision Making II1 Apr 2018MP51-10 PROSTATE CANCER NAVIGATION AND TIME TO TREATMENT Emily C. Serrell, Moritz Hansen, Andrew Perry, Melanie Feinberg, Tracy Robbins, Scot Remick, Lisa Beaule, Tom Kinkead, Paul K.J. Han, and Jesse D. Sammon Emily C. SerrellEmily C. Serrell More articles by this author , Moritz HansenMoritz Hansen More articles by this author , Andrew PerryAndrew Perry More articles by this author , Melanie FeinbergMelanie Feinberg More articles by this author , Tracy RobbinsTracy Robbins More articles by this author , Scot RemickScot Remick More articles by this author , Lisa BeauleLisa Beaule More articles by this author , Tom KinkeadTom Kinkead More articles by this author , Paul K.J. HanPaul K.J. Han More articles by this author , and Jesse D. SammonJesse D. Sammon More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1641AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Patient navigation has been shown to decrease time to diagnosis and treatment of several solid-organ malignancies. However, little is known about the effect of navigation on prostate cancer care. In 2008 our health system developed a navigation program to reduce barriers to treatment and facilitate shared decision making in a prostate cancer population. We hypothesized that navigation would decrease time to treatment or decision of active surveillance. METHODS All men diagnosed with localized prostate cancer between 2009 and 2015 were abstracted from a multi-specialty tumor registry. Duration from diagnosis to treatment or decision of surveillance was divided into quartiles. Multivariable regression analyses and Cox proportional hazards regressions controlling for patient-, disease-, and system-level factors were performed. Interaction terms evaluated the relationship between navigation, time to treatment, and patient- and disease- factors. RESULTS Of the patient population (n=1,587), 85% of men were navigated, and the median duration from diagnosis to treatment decision was 77 days (IQR: 49-110). In the top quartile of time to care (n=410), median duration was 140 days (IQR: 120-183). Factors associated with time to treatment are in Table. Navigation was significantly associated with longer time to treatment (OR=1.65, 95% CI 1.12-2.45). Interaction terms demonstrated that the relationships between navigation and time to care was independent and not moderated by cancer risk, travel distance, income, insurance, or treatment type. CONCLUSIONS The patient navigator identified and removed potential barriers to prostate cancer care. Notwithstanding, navigation was associated with longer time to treatment. This may reflect clinically appropriate delays associated with greater shared decision-making and consultation with multiple specialists. Unlike other solid-organ cancers, time to treatment may not be the ideal metric for evaluating navigation in prostate cancer; shared decision-making, patient satisfaction, and psychosocial outcomes may be more appropriate. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e688-e689 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Emily C. Serrell More articles by this author Moritz Hansen More articles by this author Andrew Perry More articles by this author Melanie Feinberg More articles by this author Tracy Robbins More articles by this author Scot Remick More articles by this author Lisa Beaule More articles by this author Tom Kinkead More articles by this author Paul K.J. Han More articles by this author Jesse D. Sammon More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

A population-based study examining the influence of a specialized rapid-access cancer clinic on initial treatment choice in localized prostate cancer.

Treatment decisions in localized prostate cancer are complicated by the available choices. A rapid-access cancer clinic (RAC) has been unique to Calgary, AB, since 2007. This RAC offers multidisciplinary prostate cancer education by a urologist, medical oncologist, and radiation oncologist. It is hypothesized that treatment utilization data from decisions taken at RAC may serve to benchmark the appropriateness of treatment decisions on a population level. Records of patients with clinically localized prostate cancer in Alberta between October 1, 2007 and September 30, 2009 were reviewed with ethics approval. Records were linked to the Alberta Cancer Registry database. Clinical, treatment, and health services characteristics pertaining to patients attending RAC were compared to the general population. The primary endpoint was utilization rates of each initial treatment. During this two-year period, 2838 patients were diagnosed with localized prostate cancer; 375 attended RAC. The utilization rates among RAC patients vs. the whole Alberta population were: prostatectomy 60.3% (95% confidence interval [CI] 55.3-65.2) vs. 48.0% (95% CI 47.1-50.7; χ2 p<0.001); active surveillance 16.0% (95% CI 12.3-19.7%) vs. 13.5% (95% CI 12.2-15.8; χ2 p=0.214); radiotherapy 11.7% (95% CI 8.5-15.0) vs. 18.0% (95% CI 16.9-20.5; χ2 p=0.002); and hormone therapy 8.0% (95% CI 5.2-10.8) vs. 17.4% (95% CI 16.1-18.9; χ2 p<0.001). A specialized clinic for localized prostate cancer may be associated with a higher likelihood of receiving surgery or active surveillance as initial treatment compared to the prostate cancer population in Alberta.

Metformin, Asian ethnicity and risk of prostate cancer in type 2 diabetes: a systematic review and meta-analysis

BackgroundMetformin is associated with a reduced risk of some cancers but its effect on prostate cancer is unclear. Some studies suggest only Asians derive this benefit. Therefore, we undertook a systematic review with particular attention to ethnicity.MethodsMedline, Embase, Scopus, Web of Science, and EBM Reviews were searched from inception to 2015. Two reviewers identified and abstracted articles. Studies were pooled using random effects model and stratified by Western- vs Asian-based populations.ResultsWe identified 482 studies; 26 underwent full review. Of Western-based studies (n = 23), two were randomized trials and 21 were observational studies. All Asian-based studies (n = 3) were observational. There were 1,572,307 patients, 1,171,643 Western vs 400,664 Asian. Across all studies there was no association between metformin and prostate cancer (RR: 1.01, 95%CI: 0.86-1.18, I2: 97%), with similar findings in Western-based trials (RR: 1.38, 95%CI: 0.72-2.64 I2: 15%) and observational studies (RR: 1.03 95%CI: 0.94-1.13, I2: 88%). Asian-based studies suggested a non-significant reduction (RR: 0.75, 95%CI: 0.42-1.34, I2: 90%), although these results were highly influenced by one study of almost 400,000 patients (propensity-adjusted RR: 0.47 95%CI 0.45-0.49). Removing this influential study yielded an estimate more congruent with Western-based studies (RR: 0.98 95%CI:0.71-1.36, I2: 0%).ConclusionThere is likely no association between metformin and risk of prostate cancer, in either Western-based or Asian-based populations after removing a highly influential Asian-based study.