Prostate Cancer Morbidity Research Articles

Abstract B045: Exosomal microRNAs are associated with prostate cancer aggressiveness in African American patients

Abstract Background: The morbidity and mortality rates of prostate cancer (PCa) in African American (AA) are 2-3 times higher than European American (EuA) men. The molecular mechanisms underlying the aggressiveness of PCa have not fully identified. Thus, our aim was to evaluate the diagnostic/prognostic utility of exosomal microRNAs (miRs) to classify PCa patients according their race and aggressive phenotype in AA patients. Their functional role in tumor aggressiveness was also determined. Methods: Exosomes were isolated from the conditioned media of AA and EuA PCa cell lines. The expression of miRs was validated in exosomes, free-circulating plasma, and FFPE tissue specimens of forty AA and EuA patients using quantitative real-time PCR analysis. The sensitivity and specificity of exosomal miRs to classify prostate cancer patients according their race and aggressiveness were assessed using receiver operating characteristic (ROC) curve analysis. To study the functional significance of exosomal miRs, cell proliferation, clonogenic, cell cycle and migration assays were performed in PCa cells transfected with miR-3128. Results: Differential expression of exosomal miR-3613-3p, miR-3218, miR-3679, and miR-3680 was demonstrated in the plasma of AA versus EuA of PCa patients. While exosomal miR-3613 and miR-3679 (p<0.05) were upregulated, free-circulating miRs downregulated (p<0.05) in the plasma of AA versus EuA patients. The accuracy of miR-3679 to discriminate AA from EuA was improved when combined with the other three miRs (AUC jumped from 0.717 to 0.897). Intriguingly, miR-3128 showed a dual role in AA versus EuA cells. Overexpression of miR-3128 increased the cell growth in AA cells while it did the opposite in EuA cells. These data were recapitulated by migration, cell cycle and clonogenic assays. Conclusion: Our findings underline the role of exosomal miRs in health disparity of PCa. The differential expression of miRs in AA men demonstrates their reliability as biomarkers and their potential role in promoting tumor aggressiveness in AA men. Citation Format: Hamdy E.A. Ali, Rofaida Gaballa, Andrew S. Sholl, Mohamed Gaballah, Juan J. Bustamante, Preeti Zanwar, Hamed I. Ali, Zakaria Y. Abd Elmageed. Exosomal microRNAs are associated with prostate cancer aggressiveness in African American patients [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 B045.

Эпидемиологические особенности рака предстательной железы в Дальневосточном федеральном округе

Background. Recent decades in the Far East Federal District have been characterized by a constant increase in the number of patients with oncological pathology, in the structure of which prostate tumors are the second largest cause of mortality in men. The goal of this study was a scientific assessment of the main rates of morbidity and mortality of prostate cancer in the male population in the Far East Federal District for the last ten years (2009–2018). Material and methods. During the study, the indicators of morbidity and mortality, reporting forms of statistical registration of oncological patients and regulatory documents of higher-level organizations, information on ten-year observations of the dynamics of changes in digital indicators of the investigated pathology were used. Results of the research. The main rates of morbidity and mortality of prostate cancer patients in the Far East Federal District are given, where 33,111 new cases of malignant neoplasms were registered in 2018, that is 24,6 % higher than ten years ago (20 191 people in 2009). In Russia, such increase was 21,6 % higher. 9 324 patients, i.e. 0,12 % population of the region, were under medical supervision. The number of patients with I-II stages of the disease (60,9 %) increased during the investigated period with simultaneous reduction of the number of patients with neglected forms (38,1 %) of the disease. Morbidity and mortality rates have been increasing steadily over the past 10 years. The percentage of actively identified patients has increased, as well as the year-end accumulation index. Morphological confirmation of the diagnosis (over 95 %) did not exceed the average republican indicators (95,9 %). The proportion of patients registered for 5 years or more was lower than averagely in Russia, but mortality rates improved in the first year from the time of the initial diagnosis (2009 – 17,3 %; 2018 – 10,1 %; Russian Federation – 7,8 %). As far as the localizations in the male reproductive organs, neglected prostate cancer remains at the highest level.

A PSCA/PGRN-NF-κB-Integrin-α4 Axis Promotes Prostate Cancer Cell Adhesion to Bone Marrow Endothelium and Enhances Metastatic Potential.

Distant metastasis, predominantly to bone, is the leading cause of morbidity and mortality in prostate cancer. However, the mechanisms underlying prostate cancer metastases remain unknown. Prostate cancer cells exhibited discrete adhesion to bone marrow endothelial cells (BMEC), resulting in osteotropic metastasis. Prior data showed an increased metastatic propensity of prostate stem cell antigen (PSCA)-positive prostate cancer cells. The current study sought to characterize the roles of PSCA in the adhesion of prostate cancer cells to BMECs. Cell adhesion was assessed using the adhesion assay and transendothelial migration. The expression and regulation of integrins were evaluated by qRT-PCR, Western blot, promoter-luciferase activity, and chromatin immunoprecipitation (ChIP). Functionally, the potential interacting partners of PSCA in prostate cancer cells were identified by coimmunoprecipitation and mass spectrometry (MS) analysis. The association of PSCA expression with bone metastasis was further analyzed in an in vivo model and prostate cancer patients. We found that overexpression of PSCA enhanced the adhesion capability of prostate cancer cells to BMECs through upregulating integrin-α4 expression, concurrent with transcriptionally activated NF-κB. Growth factor progranulin (PGRN) was identified as a potential interacting partner of PSCA in prostate cancer cells. Functional studies showed that downregulation of PGRN and PSCA with siRNAs in prostate cancer cells significantly suppressed the integrin-α4 expression and the adhesion to BMECs in vitro, respectively, which were restorable by exogenous PGRN. Importantly, PSCA depletion significantly reduced tumors' presence in the bone of a mouse model. Furthermore, PSCA expression is elevated in prostate cancer tissue, and significantly associated with increased Gleason score, advanced stage, bone metastasis, and poor prognosis in prostate cancer patients. We conclude that PSCA/PGRN promoted the adhesion of prostate cancer cells to BMECs through NF-κB/integrin-α4 pathways, to facilitate metastases. IMPLICATIONS: The findings presented here suggest PSCA/PGRN as a potential therapeutic target for prostate cancer metastases, especially for bone metastasis.

18F-NaF PET/CT and Extraordinary Involvement: Non-calcific Brain Involvement in a Prostate Cancer Case

With the increase in the diagnosis of the cancer, the frequency of using imaging methods for diagnosis and for staging is also increased. Because of the complex structure of cancer and tumor behavior, the assessment methods have been updated and metabolic imaging has gained weight. The most popular of these techniques is hybrid positron emission tomography/computed tomography (PET/CT) systems. Prostate cancer is the second most common cancer in the world, is the fifth common type in cancer-related male deaths. Estimation of prognosis and treatment planning of the patients are based on the TNM classification. Bone metastasis is a prognostic factor of morbidity and mortality in prostate cancer. Sodium fluoride (NaF) PET/CT is a promising imaging modality in evaluation of skeletal system. This article will review the involvement of 18F-NaF in extra-osseous tissues in the prostate cancer and reveal the fundamental differences between 18F-NaF imaging and 18F-FDG imaging in these areas.

Morbidity of prostate cancer, kidney cancer, bladder cancer in Russia and Omsk region

Morbidity of prostate cancer, kidney cancer, bladder cancer in Russia and Omsk region

Awareness on prostate cancer and screening practices among men attending outpatient at a referral hospital in Kigali, Rwanda: A quantitative study

BackgroundProstate cancer is estimated to be the second of all under diagnosed cancer and it is ranged the sixth among the cause of cancer mortality worldwide. The sensitization related to prostate cancer awareness and its screening needs to be encouraged among adult men to avoid late consultation and reduce prostate cancer morbidity and mortality. Purpose of the studyTo assess prostate cancer awareness and screening practices among adult males attending outpatient department at Kigali university teaching hospital, Rwanda. MethodologyA quantitative, descriptive cross-sectional design was used in this study. A systematic random sampling technique was used to select 257 adult males, who participated in the study. Participants were chosen from among the men who consulted urology and general surgery services at University Teaching hospital of Kigali (CHUK) Rwanda, during 8 weeks of the study period. ResultsAmong 257 participants in the study, the great proportion (43%) of respondents ranged between 51 and 60. 80% of the respondents were aware of prostate cancer existence and reported the health provider as being the major source of the information. Knowledge on various domains was low and 64% of the respondents were not aware of the risk factors of prostate cancer, 32% did not know the prevention measures of prostate cancer, 64% of the respondents were aware of prostate cancer screening using PSA exam and 49% of the respondents had undergone screening by performing PSA exam. Overall prostate cancer awareness and screening practice was 75% and 49.5% respectively. Having a university level education was significantly associated with P Ca awareness and screening practices (p < 0.004), and working in public institutions had a strong correlation to Prostate cancer awareness and screening practice (p < 0.000). ConclusionThe level of awareness of prostate cancer was high while knowledge on some areas was low. Screening practices were found to be poor, almost half of participants did not perform PSA test. There is a need to improve health education to the community regarding prostate cancer to enhance knowledge and increase the rate of screening.

Using the theory of precision medicine to optimize the multidisciplinary comprehensive treatment of prostate cancer

In recent years, morbidity and mortality of prostate cancer in China have increased rapidly, and it has become a common malignant tumor among the top 5 male tumors in some areas. Multidisciplinary comprehensive treatment is the key to improve the survival rate and quality of life of prostate cancer. However, the drugs used to construct multidisciplinary comprehensive treatment were based on anatomy, treatment stage and clinical trials, which lacked individualized treatment for complex tumor scenarios. With the rapid development of precision medicine, molecular imaging, molecular typing and pharmacogenomics will be added to these three elements, which will help to improve the individualized level of multidisciplinary comprehensive treatment. This kind of precise multidisciplinary comprehensive treatment urgently needs the vigorous promotion of ideas, researchers and researches.

THE CHARACTERISTICS OF ONCO-UROLOGICAL MORBIDITY OF MOSCOW POPULATION IN 2006-2015

The article presents the analysis of trends specific for onco-urological morbidity of Moscow population on the basis of data of official statistical reports for 2006-2015. It is established that prostate cancer is the most actual onco-urological problem in Moscow. The level of morbidity of prostate cancer in the capital exceeds the corresponding average level in the Russian Federation. During 2006-2015, the morbidity of prostate cancer in Moscow increased up to 33.6% i.e. from 52.7 to 70.4 cases per 100 000 of male population. In Moscow, in 2015, morbidity of kidney cancer made up to 11.73 and bladder cancer - 9.72 cases per 100 000 of population. As compared with 2006, morbidity of prostate cancer decreased up to 3.1% and morbidity of bladder cancer increased up to 9.2%. In Moscow, for morbidity of prostate cancer and bladder cancer are specific lower levels in comparison with national average indices. It is demonstrated that efficiency of target oncologic preventive examinations, timeliness of detection of onco-urological diseases and also efficiency of their treatment in Moscow is higher than in the Russian Federation on the whole. At that, in Moscow 31.6% of cases of prostate cancer, 29,7% of cases of kidney cancer and 17.7% of bladder cancer are detected at stage III-IV of disease. The results of implemented study testify necessity of development of urological care of population, including its out-patient section that effects efficiency and timeliness of detection and effectiveness of treatment of onco-urological diseases.

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.

Family history in primary hormone therapy for prostate cancer from a community-based multi-institutional Japan-wide database.

e16549 Background: Although a positive family history is known to increase the risk of morbidity of prostate cancer, little is known about the prognoses with hormone therapy of individuals with familial prostate cancer. Thus, in this study we aimed to determine the associations between hormone therapy and outcomes of a cohort of men with familial prostate cancer from a large community-based multi-institutional Japan-wide registry. Methods: Data of patients with prostate cancer who had received hormone therapy were extracted from a nationwide community-based database established by the Japan Study Group for Prostate Cancer. Family history of prostate cancer was available for 15,873 of these patients, who thus comprised the study cohort. Prognostic variables, including progression-free survival, cancer-specific survival, and overall survival, were compared between men with familial and men with sporadic prostate cancer. Results: A positive family history was identified in 247 patients (1.6%). Patients with a positive family history were younger than those without; however, other clinicopathological characteristics and prognoses were comparable. In subgroup analysis, family history was identified as a significant favorable prognostic factor for progression-free survival among patients treated by castration, as was overall survival among patients with PSA level at diagnosis less than 100 ng/mL and those with low or intermediate J-CAPRA risk. Conclusions: Our findings indicate that familial prostate cancer has an early-onset feature or is diagnosed earlier than sporadic prostate cancer. However, with hormone therapy the prognoses of individuals with familial prostate cancer are comparable to those of individuals with sporadic prostate cancer.

Early Stage Biomarkers Screening of Prostate Cancer Based on Weighted Gene Coexpression Network Analysis.

Although the morbidity and mortality rates of prostate cancer (PCa) are considerably high, many PCas are characterized as indolent and slow growing, which do not require overtreatment. Overdiagnosis and overtreatment of early detected PCa are an emerging problem, owing to a lack of biomarkers that detect advanced disease at an earlier stage. In this study, RNA-Seq data of 57,045 genes for 495 PCa samples and 52 normal samples in the The Cancer Genome Atlas (TCGA) database were downloaded. Subsequently, we performed weighted gene coexpression network analysis to identify the Gleason score-related coexpression gene module, and further screened out oncogenes and tumor suppressors that were upregulated or downregulated in the early stage of PCa as well as those related to the clinical prognosis of PCa patients. Based on this study, some novel biomarkers were identified for the disease-free survival, which are helpful for fast diagnosis and prognosis.

Screening Prostate-Specific Antigen and Early Detection

Prostate cancer early detection based on screening with prostate-specific antigen (PSA) has been a highly controversial topic over the years. Early detection and treatment of high-risk prostate cancer explains a large proportion of greater than 50% reduction in age-standardized prostate cancer mortality observed since the early 1990s. However, this public health success has come at the cost of high levels of overdiagnosis of low-risk tumors, and many men have suffered from overtreatment of these entirely indolent lesions. Data from randomized trials increasingly clearly indicate a prostate cancer mortality advantage with screening. Other cohort studies, moreover, suggest that an early, baseline PSA test around age 45 or 50 years can predict cancer risk over years and decades, potentially allowing subsequent screening intervals to be personalized, further reducing both over- and underdiagnosis. Other aspects of a smarter screening paradigm include focused attention on men at higher risk based on ancestry, family history, and other factors; consideration of other variables together with PSA; selective use of secondary testing with emerging blood and urine tests; and reservation of treatment only for men at risk of prostate cancer mortality. Such an approach should be able to reduce further prostate cancer morbidity and mortality, while minimizing the harms of over-diagnosis and overtreatment. This review contains 4 figures, 1 table, and 88 references. Key Words: Prostate cancer, prostate-specific antigen, early detection, cancer screening, guidelines, risk stratification, epidemiology, PLCO, ERSPC, USPSTF, CISNET

The human oncogene SCL/TAL1 interrupting locus (STIL) promotes tumor growth through MAPK/ERK, PI3K/Akt and AMPK pathways in prostate cancer

The morbidity and mortality of prostate cancer (PCa) in China have increased obviously, which became the second leading cause of death in men with cancer. Hedgehog (Hh) signaling pathway is a key signaling pathway involved in the prostate cancer progression. The human oncogene SCL/TAL1 interrupting locus (STIL) can modulate the Hh signaling pathway, but its function in PCa has not been reported. Here, we showed that STIL was increased in high grade prostate cancer tissue. Knockdown of STIL in prostate cancer cells PC-3 and DU 145 significantly decreased the proliferation of cells and induced cellular apoptosis through casepase3/7 mediated pathway. Moreover, the colony formation ability was also inhibited when knockdown of STIL by lentivirus-mediated shRNA. Furthermore, the cellular signaling antibody array analysis revealed which signaling pathway was affected when silencing STIL. Altogether, we found that STIL could affect MAPK/ERK, PI3K/Akt and AMPK signaling pathways, thus promoting cellular proliferation, colony formation and suppressing cellular apoptosis in prostate cancer.

Prostate-Derived Ets Factor (PDEF) Inhibits Metastasis by Inducing Epithelial/Luminal Phenotype in Prostate Cancer Cells.

Metastasis is the primary cause of prostate cancer morbidity and mortality. Our previous studies revealed that Sam pointed domain ETS transcription factor, a.k.a. prostate-derived ETS factor (SPDEF/PDEF), inhibits prostate cancer metastasis. However, the mechanism is still unclear. In this study, using microarray and gene set enrichment analysis, we discovered that PDEF upregulated epithelial/luminal differentiation-related genes while it suppressed stemness and epithelial-to-mesenchymal transition-related genes, especially Twist1. We also observed loss of PDEF and gain of Twist1 expression during prostate cancer progression in the TRAMP mouse model. Moreover, Twist1 knockdown resulted in upregulation of PDEF expression, suggesting a reciprocal regulation between PDEF and Twist1. Mechanistically, our ChIP-seq analysis revealed that PDEF directly regulated cytokeratin 18 (CK18) transcription through the GGAT motif within its putative promoter region. CK18 knockdown resulted in increased expression of Twist1, suggesting that PDEF regulated Twist1 in part via CK18. Our analysis of multiple clinical prostate cancer cohorts revealed an inverse relationship between PDEF expression and tumor grade, tumor metastasis, and poor patient survival. Furthermore, a two-gene signature of low PDEF and high Twist1 can better predict poor survival in prostate cancer patients than either gene alone. Collectively, our findings demonstrate PDEF inhibits prostate tumor progression, in part, by directly regulating transcription of CK18, and that PDEF/Twist1 expression could help distinguish between lethal and indolent prostate cancer.Implications: This study reports the novel findings that PDEF suppresses Twist1 partly via CK18 and that PDEF/Twist1 could help distinguish between lethal and indolent prostate cancer.Visual Overview: http://mcr.aacrjournals.org/content/molcanres/16/9/1430/F1.large.jpg Mol Cancer Res; 16(9); 1430-40. ©2018 AACR.

Downregulation of miR-133a-3p promotes prostate cancer bone metastasis via activating PI3K/AKT signaling

BackgroundBone metastasis is a leading cause of morbidity and mortality in advanced prostate cancer (PCa). Downexpression of miR-133a-3p has been found to contribute to the progression, recurrence and distant metastasis in PCa. However, clinical significance of miR-133a-3p in bone metastasis of PCa, and the biological role of miR-133a-3p and its molecular mechanisms underlying bone metastasis of PCa remain unclear.MethodsmiR-133a-3p expression was evaluated in 245 clinical PCa tissues by real-time PCR. Statistical analysis was performed to evaluate the clinical correlation between miR-133a-3p expression and clinicopathological features, and overall and bone metastasis-free survival in PCa patients. The biological roles of miR-133a-3p in the bone metastasis of PCa were investigated both in vitro and in vivo. Bioinformatics analysis, real-time PCR, western blot and luciferase reporter analysis were applied to demonstrate the relationship between miR-133a-3p and its potential targets. Western blotting and luciferase assays were examined to identify the underlying pathway involved in the anti-tumor role of miR-133a-3p. Clinical correlation of miR-133a-3p with its targets was verified in human PCa tissues.ResultsmiR-133a-3p expression is reduced in PCa tissues compared with the adjacent normal tissues and benign prostate lesion tissues, particularly in bone metastatic PCa tissues. Low expression of miR-133a-3p is significantly correlated with advanced clinicopathological characteristics and shorter bone metastasis-free survival in PCa patients by statistical analysis. Moreover, upregulating miR-133a-3p inhibits cancer stem cell-like phenotypes in vitro and in vivo, as well as attenuates anoikis resistance in vitro in PCa cells. Importantly, administration of agomir-133a-3p greatly suppresses the incidence of PCa bone metastasis in vivo. Our results further demonstrate that miR-133a-3p suppresses bone metastasis of PCa via inhibiting PI3K/AKT signaling by directly targeting multiple cytokine receptors, including EGFR, FGFR1, IGF1R and MET. The negative clinical correlation of miR-133a-3p with EGFR, FGFR1, IGF1R, MET and PI3K/AKT signaling activity is determined in clinical PCa tissues.ConclusionOur results unveil a novel mechanism by which miR-133a-3p inhibits bone metastasis of PCa, providing the evidence that miR-133a-3p may serve as a potential bone metastasis marker in PCa, and delivery of agomir-133a-3p may be an effective anti-bone metastasis therapeutic strategy in PCa.

Abstract C04: Impact of a Minority Prostate Cancer (MiCaP) Research Digest in translating scientific discovery into public health and community applications

Abstract Background and Objective: Although prostate cancer (CaP) mortality and morbidity have declined since the 1990s, Black men (BM) are still disproportionately affected by CaP. It will take a concerted and inventive effort to address the burden of CaP in BM. A unique approach that is of significant interest to our team is increased access to life-changing, scientific CaP discoveries for BM, especially those with implications for primary and secondary preventive interventions. The primary objective of this study was to develop a research dissemination program, the Minority Prostate Cancer (MiCaP) Research Digest, which will spread information about CaP scientific discoveries, evidence-based interventions, and open clinical trials instantly among BM. We hypothesized that knowledge, attitude, perceived behavioral control, cues to action, and risk-reduction and prevention behaviors will be higher among the users of the MiCaP Research Digest compared to nonusers. Methodology: The development of the MiCaP Research Digest was guided by valid behavioral and health communication models and based on an understanding of the scientific information needs of BM. The targeted population was BM between the ages of 35 and 70 years. The research setting was in Florida. We employed focus groups and individual interviews to plan and select the strategy, channel, and material for the digest. Subsequently, the communication strategy statement was used to develop message concepts and materials. A cross-sectional pre- post study design was employed to establish the efficacy of the Digest among 33 BM. Results: The Digest comprised a one-page public abstract and a 7-minute video that includes: (1) Digest Minute sound bite by the author; (2) 4-minute discussion with the author taking questions from a CaP advocate and a peer scientist; (3) Digest Minute recap by the scientist and advocate; and (4) a clinical trial opportunity session. The first volume focused on “Prostate tumor gene expression in Black men.” Majority of the 33 participants who previewed the Digest were native-born BM, between 60 and 69 years, had college degrees, were married, and had full-time employment. Based on McNemar's test results of pre- and post-assessments, there was significant improvement in the knowledge and self-efficacy of participants. In rating the Digest, 100% of participants were satisfied with it, 96% rated the digest information as satisfactory, 87% rated it as better than expected, and 97% rated the quality as high. Participants' written feedback was also very positive. Conclusion: Although many biomedical research projects are funded through public dollars, oftentimes the scientific discoveries from the projects are inaccessible for the public. This is especially disconcerting when such discoveries can have immediate impact on a disease that disproportionately affects a specific population, Black men (BM). The MiCaP Research Digest provides a vehicle for BM to access high-impact CaP scientific discoveries, thereby facilitating the immediate translation of scientific discoveries into public health applications. Citation Format: Folakemi Odedina, Kim Walsh-Childers, Mary Ellen Young, Getachew Dagne, Janice Krieger, Ernest Kaninjing, Nissa Askins. Impact of a Minority Prostate Cancer (MiCaP) Research Digest in translating scientific discovery into public health and community applications [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr C04.

Expression of Indoleamine 2,3-Dioxygenase Induced by IFN-γ and TNF-α as Potential Biomarker of Prostate Cancer Progression.

Inflammation has been suggested to play an important role in onset and progression of prostate cancer (PCa). Histological analysis of prostatectomy specimens has revealed focal inflammation in early stage lesions of this malignancy. We addressed the role of inflammatory stimuli in the release of PCa-specific, tumor-derived soluble factors (PCa-TDSFs) already reported to be mediators of PCa morbidity, such as indoleamine 2,3-dioxygenase (IDO) and interleukin (IL)-6. Inflammation-driven production and functions of PCa-TDFSs were tested “in vitro” by stimulating established cell lines (CA-HPV-10 and PC3) with IFN-γ or TNF-α. Expression of genes encoding IDO, IL-6, IFN-γ, TNF-α, and their receptors was investigated in tumor tissues of PCa patients undergoing radical prostatectomy, in comparison with benign prostatic hyperplasia (BPH) specimens. IFN-γ and TNF-α-treatment resulted in the induction of IDO and IL-6 gene expression and release in established cell lines, suggesting that the elicitation of PCa-TDSFs by these cytokines might contribute to progression of cancer into an untreatable phenotype. An analysis based on timing of biochemical recurrence revealed the prognostic value of IDO but not IL-6 gene expression in predicting recurrence-free survival in patients (RFS) with PCa. In addition, a urine-based mRNA biomarker study revealed the diagnostic potential of IDO gene expression in urines of men at risk of PCa development.

Author Reply

The commentator underscores several important points. First, since the United States Preventive Services Task Force recommendation to eliminate PSA screening, there has been an increased incidence of more clinically aggressive prostate cancers. Second, although the current data shows that with PSA screening at 12-18 months intervals, prostate cancer morbidity can be substantially reduced, it is critically important to mitigate the impact of unnecessary treatment by utilizing active surveillance, and various newer methods for risk stratification of patients with low-grade, low-stage disease.

Self-reported sleep disturbances and prostate cancer morbidity and mortality in Swedish men: A longitudinal study over 40years.

The present study, with an observational period of about 40years, examined the association between self-reported sleep disturbances (i.e. problems with falling and staying asleep; use of hypnotics) and prostate cancer morbidity and mortality in initially 2322 men (all 50years old at baseline). Self-reported sleep disturbances and established risk factors (e.g. age, lower urinary tract symptoms, smoking and family history of cancer) were measured at ages 50 and 70years. Information about prostate cancer diagnosis and deaths as a result of prostate cancer was available from the National Cancer Registry and the Swedish Civil Registry of Morbidity. During the observational period, 263 participants developed prostate cancer (11% of the total cohort); 146 of them died as a result of prostate cancer. There was no association between sleep disturbances and prostate cancer morbidity or mortality (hazard ratio 1.09, 95% confidence interval (CI) 0.79, 1.52, and hazard ratio 1.21, 95% CI 0.77, 1.91, respectively). Similar findings were observed when examining associations between single sleep disturbance parameters and prostate cancer morbidity and mortality. Our study does not provide evidence that reports of sleep disturbances increase the risk of prostate cancer morbidity or mortality in middle to older-aged men. Therefore, assessing subjective sleep problems may not meaningfully help to identify men at risk of developing prostate cancer or dying of this devastating condition.

(P21) Health Disparities and Inequities in Radiation Therapy for Prostate Cancer

Well-documented health disparities exist in prostate cancer (PCa) incidence, healthcare resource utilization, and mortality. However, inequities in PCa radiation therapy (RT) specifically have not yet been comprehensively summarized. To review and summarize the reported health disparities and inequities in healthcare resource utilization for PCa undergoing RT. A comprehensive literature search in the PubMed database was generated with the query “prostate AND (radiation OR radiotherapy OR proton) AND (disparities OR “socioeconomic status” OR “health services research” OR inequity OR race[Title])”. Studies were included if they examined RT or related resource utilization and addressed health inequities in the United States. The initial query returned 281 studies with 79 meeting inclusion criteria. These consisted of 67 population-based analyses, 5 single-institution analyses, 3 prospective studies, 3 survey-based studies, and 1 multi-institutional review. Of the population-based analyses, 13 studies used the National Cancer Database (NCDB) and 37 studies used Surveillance, Epidemiology, and End Results (SEER) databases; the remainder used state specific registries and Medicare and Veterans Affairs databases. Studies were published between 1991 and 2017, with 62 of 79 (78%) published after 2010. The most common health inequities reported pertained to age (23 studies), race and ethnicity (60), socioeconomic status (22), insurance status (18), and hospital or practice characteristics (24). These variables resulted in inequities in: screening and staging methods (3 studies) and management approach and treatment intent (44), e.g. definitive versus non-definitive management. Inequities in radiation modality type, including intensity-modulated RT (IMRT), proton therapy, brachytherapy, and stereotactic body RT (SBRT) were assessed in 43 studies. Increased age was generally associated with a decreased likelihood of receiving definitive treatment. For instance, one SEER study of 86,544 patients diagnosed with localized PCa between 2006-2011 demonstrated that patients age 80-89 received curative treatment less frequently than those age 66-79, even with adjustment for comorbidity and performance status (OR 0.18). Non-white race was generally associated with decreased healthcare resource utilization in multiple aspects. For example, for initial staging, black patients with low risk PCa were less likely to undergo multiparametric MRI in one single-institution analysis of 705 patients from 2005-2013 (OR 0.51). Black patients were less likely to receive definitive therapy, even after adjustment for income, education, and insurance status. Among RT modalities, black patients received proton therapy and brachytherapy less frequently than white patients. Additionally, the time from diagnosis to definitive treatment was longer for black patients, especially in high risk disease. Similar inequities were also observed in Hispanic, Asian, and Pacific Islander patients. Lower socioeconomic status and insurance status (i.e. Medicaid/no insurance versus Medicare/private plans) were independently associated with decreased likelihood of receiving definitive therapy and increased likelihood of receiving RT versus prostatectomy. With regards to practice setting, academic cancer centers notably exhibited similar health inequities to community cancer centers. Significant inequities in the utilization of RT for PCa exist, with the most published RT outcomes pertaining to age, race, socioeconomic status, insurance status, and practice setting. These inequities likely contribute to disparities in overall PCa morbidity and mortality.