Prostate Cancer[JOURNAL]
Sun
200 papers
Knowledge, Perceived Risk and Utilization of Prostate Cancer Screening Services among Men in Dar Es Salaam, Tanzania.
Bugoye FC, Leyna GH, Moen K … +1 more , Mmbaga EJ
Prostate Cancer · 2019 · PMID 31871794 · Full text
BACKGROUND: Late diagnosis of prostate cancer is common in low and middle income countries and contributes to high morbidity and mortality of the disease. Utilization of prostate cancer screening services plays a major r...
BACKGROUND: Late diagnosis of prostate cancer is common in low and middle income countries and contributes to high morbidity and mortality of the disease. Utilization of prostate cancer screening services plays a major role in prevention of adverse outcomes. However, there is limited information on the knowledge about, the perceived risk of, and the utilization of prostate cancer screening in Tanzania. OBJECTIVE: To determine knowledge and perceived risk of prostate cancer, and the utilization of prostate cancer screening services, and associated factors, among men in Dar es Salaam, Tanzania. DESIGN: A population-based cross-sectional study involving men aged 40 years and above living in Dar es Salaam was conducted between May and August, 2018. METHODOLOGY: Participants were recruited through multistage random sampling and took part in structured face-to-face interviews. Categorical variables were summarized using proportions while continuous variables were summarized as medians and inter-quarterly range (IQR). Chi square test was used to compare differences between proportions, and logistic regression modelling was used to determine factors associated with utilization of prostate cancer screening. Both crude and adjusted odds ratios (OR), with corresponding 95% confidence intervals, are reported. All analyses were two-tailed and the significance level set at 5%. RESULTS: A total of 388 men with a median age of 53 years (IQR 44-55) participated. Half (52.1%) had poor knowledge about prostate cancer and prostate cancer screening. A third (32.3%, = 125) perceived the risk of prostate cancer to be low. Only 30 respondents (7.7%) had ever been screened for prostate cancer. Utilization of prostate cancer screening services was independently associated with age above 60 years [AOR = 21.46, 95% CI: 6.23, 73.93], monthly income above 305 US Dollars [AOR = 15.68, 95% CI: 4.60, 53.48], the perceived risk of prostate cancer [AOR = 16.34, 95% CI: 7.82, 14.92] and knowledge about prostate cancer [AOR = 67.71, 95% CI: 8.20, 559.57]. CONCLUSIONS: Knowledge about prostate cancer and prostate cancer screening services was low among men in Dar es Salaam with a third perceiving themselves to be at no risk for the disease. Utilization of screening services was low and associated with low income, younger age, low perceived risk of prostate cancer and low knowledge about the disease. Intervention measures aiming to increase knowledge about prostate cancer and screening services, and affordable provision of services, are urgently called for.
Achieving PSA < 0.2 ng/ml before Radiation Therapy Is a Strong Predictor of Treatment Success in Patients with High-Risk Locally Advanced Prostate Cancer.
Kazama A, Saito T, Takeda K … +8 more , Kobayashi K, Tanikawa T, Kanemoto A, Ayukawa F, Matsumoto Y, Sugita T, Hara N, Tomita Y
Prostate Cancer · 2019 · PMID 31772776 · Full text
BACKGROUND: To predict long-term treatment outcome of radiation therapy (RT) plus androgen deprivation therapy (ADT) for high-risk locally advanced prostate cancer. METHODS: In total, 204 patients with the National Compr...
BACKGROUND: To predict long-term treatment outcome of radiation therapy (RT) plus androgen deprivation therapy (ADT) for high-risk locally advanced prostate cancer. METHODS: In total, 204 patients with the National Comprehensive Cancer Network (NCCN) high risk locally advanced prostate cancer (PSA > 20 ng/ml, Gleason score ≧ 8, clinical T stage ≧ 3a) were treated with definitive RT with ADT. Median follow up period was 113 months (IQR: 95-128). Median neoadjuvant ADT and total ADT duration were 7 months (IQR: 6-10) and 27 months (IQR: 14-38), respectively. RESULTS: PSA recurrence-free survival (PSA-RFS), cancer specific survival (CSS), and overall survival (OS) rates at 5 years were 84.1%, 98.5%, and 93.6%, respectively, and 67.9%, 91.2%, and 78.1%, respectively, at 10 years. Pre-RT PSA less than 0.2 ng/ml was associated with superior outcomes of PSA-RFS (HR = 0.42, 95% CI: 0.25-0.70, = 0.001), CSS (HR = 0.27, 95% CI: 0.09-0.82, = 0.013), and OS (HR = 0.48, 95% CI: 0.26-0.91, = 0.021). On multivariate analysis, age (≥70 y.o.) and pre-RT PSA (≥0.2 ng/ml) were factors predictive of poorer OS ( = 0.032) , but iPSA, T stage, Gleason score, number of NCCN high-risk criteria, a combination with anti-androgen therapy and neoadjuvant ADT duration were not predictive of treatment outcome. CONCLUSION: In patient with high-risk prostate cancer, RT plus ADT achieved good oncologic outcomes. PSA < 0.2 ng/ml before radiation therapy is a strong independent predictor for long overall survival.
Incidence of Skeletal-Related Events in Patients with Castration-Resistant Prostate Cancer: An Observational Retrospective Cohort Study in the US.
Kawai AT, Martinez D, Saltus CW … +3 more , Vassilev ZP, Soriano-Gabarró M, Kaye JA
Prostate Cancer · 2019 · PMID 31360552 · Full text
BACKGROUND AND OBJECTIVE: Skeletal-related events (SREs) are common in men with bone metastases and have negative consequences for patients with castration-resistant prostate cancer (CRPC), including pain, reduced qualit...
BACKGROUND AND OBJECTIVE: Skeletal-related events (SREs) are common in men with bone metastases and have negative consequences for patients with castration-resistant prostate cancer (CRPC), including pain, reduced quality of life, and increased mortality. We estimated incidence rates of first SREs in a cohort of men with CRPC in the Surveillance, Epidemiology, and End Results-Medicare database. METHODS: We included men aged ≥ 65 years with a prostate cancer diagnosis in 2000-2011 if they had no prior malignancy (other than nonmelanoma skin cancer) and had surgical or medical castration with subsequent second-line systemic therapy, which was used to infer castration resistance. The first occurrence of an SRE (fracture, bone surgery, radiation therapy, or spinal cord compression) in Medicare claims was identified. Incidence rates of SREs were estimated in all eligible person-time and, in secondary analyses, stratified by any use of bone-targeted agents (BTAs) and history of SRE. RESULTS: Of 2,234 men with CRPC (84% white, mean age = 76.6 years), 896 (40%) had an SRE during follow-up, with 74% occurring within a year after cohort entry. Overall, the incidence rate of SREs was 3.78 (95% CI, 3.53-4.03) per 100 person-months. The incidence rate of SREs before any BTA use was 4.16 (95% CI, 3.71-4.65) per 100 person-months, and after any BTA use was 3.60 (95% CI, 3.32-3.91) per 100 person-months. The incidence rate in patients with no history of SRE was 3.33 (95% CI 3.01-3.68) per 100 person-months, and in patients who had such a history, it was 4.20 (95% CI 3.84-4.58) per 100 person-months. CONCLUSIONS: In this large cohort of elderly men with CRPC in the US, SREs were common. A decrease in incidence of SREs after starting BTA is suggested, but the magnitude of the effect may be confounded by indication and other factors such as age and prior SRE.
Corrigendum to "Incidence of Second Primary Malignancies in Patients with Castration-Resistant Prostate Cancer: An Observational Retrospective Cohort Study in the United States".
Saltus CW, Vassilev ZP, Zong J … +4 more , Calingaert B, Andrews EB, Soriano-Gabarró M, Kaye JA
Prostate Cancer · 2019 · PMID 31355002 · Full text
[This corrects the article DOI: 10.1155/2019/4387415.].
[This corrects the article DOI: 10.1155/2019/4387415.].
Prevalence of the Ser217Leu Variant of the ELAC2 Gene and Its Association with Prostate Cancer in Population of the Littoral Region of Cameroon.
Djomkam ALZ, Beyeme Sala T, Baari Memba C … +1 more , Njimoh DL
Prostate Cancer · 2019 · PMID 31321101 · Full text
has been identified as a prostate cancer (PC) susceptibility gene. Ser- Leu changes at amino acid 217 have been one of the most studied variants of this gene. Several reports have shown association of this variant with P...
has been identified as a prostate cancer (PC) susceptibility gene. Ser- Leu changes at amino acid 217 have been one of the most studied variants of this gene. Several reports have shown association of this variant with PC in samples of men drawn from families with hereditary PC and even sporadic cases. This study aimed at assessing this association and the prevalence of the Ser217Leu variant of ELAC2 in populations of the Littoral Region of Cameroon. 103 PC case subjects and 80 randomly selected controls identified from the study population participated in the study. 2 milliliters of blood samples was collected from each of the consented participants and used for human genomic DNA extraction and genotyping of the ELAC2 gene by the nonenzymatic salting out and PCR-RFLP methods, respectively. The frequencies of the wild type (SS), heterozygous mutant (SL), and homozygous mutant (LL) genotypes were, respectively, 28.2%, 49.5%, and 22.3% in prostate cancer patients and 28.8%, 67.5%, and 3.7% in controls. Comparing the LL with SS and (SL+LL) with SS showed that the presence of two copies of the L allele confers a high risk of prostate cancer as compared to the presence of only one L allele which presents no risk of prostate cancer (OR = 6.080 and 1.030, respectively). Analysis of our results also suggested an association ( = 0.0012) of the Ser217Leu variant with increased risk of prostate cancer. Alterations in the ELAC2 gene contribute to prostate cancer susceptibility in men living in the Littoral Region of Cameroon.
The Association of the Long Prostate Cancer Expressed PDE4D Transcripts to Poor Patient Outcome Depends on the Tumour's TMPRSS2-ERG Fusion Status.
van Strijp D, de Witz C, Heitkötter B … +7 more , Huss S, Bögemann M, Baillie GS, Houslay MD, Bangma C, Semjonow A, Hoffmann R
Prostate Cancer · 2019 · PMID 31275657 · Full text
OBJECTIVES: To investigate the added value of assessing transcripts for the long cAMP phosphodiesterase-4D (PDE4D) isoforms, PDE4D5 and PDE4D9, regarding the prognostic power of the 'CAPRA & PDE4D7' combination risk mode...
OBJECTIVES: To investigate the added value of assessing transcripts for the long cAMP phosphodiesterase-4D (PDE4D) isoforms, PDE4D5 and PDE4D9, regarding the prognostic power of the 'CAPRA & PDE4D7' combination risk model to predict longitudinal postsurgical biological outcomes in prostate cancer. PATIENTS AND METHODS: RNA was extracted from both biopsy punches of resected tumours (606 patients; RP cohort) and diagnostic needle biopsies (168 patients; DB cohort). RT-qPCR was performed in order to determine PDE4D5, PDE4D7, and PDE4D9 transcript scores in both study cohorts. By RNA sequencing, we determined the TMPRSS2-ERG fusion status of each tumour sample in the RP cohort. Kaplan-Meier survival analyses were then applied to correlate the PDE4D5, PDE4D7 and PDE4D9 scores with postsurgical patient outcomes. Logistic regression was then used to combine the clinical CAPRA score with PDE4D5, PDE4D7, and PDE4D9 scores in order to build a 'CAPRA & PDE4D5/7/9' regression model. ROC and decision curve analysis was used to estimate the net benefit of the 'CAPRA & PDE4D5/7/9' risk model. RESULTS: Kaplan-Meier survival analysis, on the RP cohort, revealed a significant association of the PDE4D7 score with postsurgical biochemical recurrence (BCR) in the presence of the TMPRSS2-ERG gene rearrangement (logrank p<0.0001), compared to the absence of this gene fusion event (logrank p=0.08). In contrast, the PDE4D5 score was only significantly associated with BCR in TMPRSS2-ERG fusion negative tumours (logrank p<0.0001 vs. logrank p=0.4 for TMPRSS2-ERG+ tumours). This was similar for the PDE4D9 score although less pronounced compared to that of the PDE4D5 score (TMPRSS2ERG- logrank p<0.0001 vs. TMPRSS2ERG+ logrank p<0.005). In order to predict BCR after primary treatment, we undertook ROC analysis of the logistic regression combination model of the CAPRA score with the PDE4D5, PDE4D7, and PDE4D9 scores. For the DB cohort, this demonstrated significant differences in the AUC between the CAPRA and the PDE4D5/7/9 regression model vs. the CAPRA and PDE4D7 risk model (AUC 0.87 vs. 0.82; p=0.049) vs. the CAPRA score alone (AUC 0.87 vs. 0.77; p=0.005). The CAPRA and PDE4D5/7/9 risk model stratified 19.2% patients of the DB cohort to either 'no risk of biochemical relapse' (NPV 100%) or the 'start of any secondary treatment (NPV 100%)', over a follow-up period of up to 15 years. Decision curve analysis presented a clear, net benefit for the use of the novel CAPRA & PDE4D5/7/9 risk model compared to the clinical CAPRA score alone or the CAPRA and PDE4D7 model across all decision thresholds. CONCLUSION: Association of the long PDE4D5, PDE4D7, and PDE4D9 transcript scores to prostate cancer patient outcome, after primary intervention, varies in opposite directions depending on the TMPRSS2-ERG genomic fusion background of the tumour. Adding transcript scores for the long PDE4D isoforms, PDE4D5 and PDE4D9, to our previously presented combination risk model of the combined 'CAPRA & PDE4D7' score, in order to generate the CAPRA and PDE4D5/7/9 score, significantly improves the prognostic power of the model in predicting postsurgical biological outcomes in prostate cancer patients.
Inhibition of Prostate Cancer Cells by 4,5-Dicaffeoylquinic Acid through Cell Cycle Arrest.
Lodise O, Patil K, Karshenboym I … +3 more , Prombo S, Chukwueke C, Pai SB
Prostate Cancer · 2019 · PMID 31263600 · Full text
Prostate cancer is a major cause of cancer-related mortality in men. Even though current therapeutic management has contributed to reducing mortality, additional intervention strategies are warranted to further improve t...
Prostate cancer is a major cause of cancer-related mortality in men. Even though current therapeutic management has contributed to reducing mortality, additional intervention strategies are warranted to further improve the outcomes. To this end, we have investigated the efficacy of dicaffeoylquinic acids, ingredients in Yerba Mate (), an evergreen cultivated in South America, the leaves of which are used to prepare a tea/coffee-like drink. Of the various analogs tested, 4,5-dicaffeoylquinic acid (4,5-diCQA) was the most active molecule against DU-145 prostate cancer cells with a 50% inhibitory concentration (IC) of 5 M. 4,5-diCQA was active both under normoxic and hypoxic conditions. The effect of 72-hour treatment on DU-145 cells persisted for an extended time period as assessed by clonogenic assay. Mechanistic studies revealed that the toxic effect was not due to induction of programmed cell death but through cell cycle arrest at S phase. Additionally, 4,5-diCQA did not impact PI3K/MAPK signaling pathway nor did it affect the depolarization of the mitochondrial membrane. 4,5-diCQA-induced accumulation of cells in the S-phase also seems to negatively impact Bcl-2 expression. 4,5-diCQA also exhibited inhibitory activity on LNCaP and PC-3 prostate cancer cells suggesting that it has therapeutic potential on a broad range of prostate cancers. Taken together, the novel inhibitory activity and mechanism of action of 4,5-diCQA opens up potential therapeutic options for using this molecule as monotherapy as well as in combinatorial therapies for the clinical management of prostate cancer.
Anesthesia for Open Radical Retropubic Prostatectomy: A Comparison between Combined Spinal Epidural Anesthesia and Combined General Epidural Anesthesia.
Kofler O, Prueckner S, Weninger E … +8 more , Tomasi R, Karl A, Niedermayer S, Jovanovic A, Müller HH, Stief C, Zwissler B, von Dossow V
Prostate Cancer · 2019 · PMID 31218084 · Full text
BACKGROUND: Several anesthesiologic regimens can be used for open radical retropubic prostatectomy. The aim of this retrospective analysis was to compare the combined general epidural anesthesia and the combined spinal e...
BACKGROUND: Several anesthesiologic regimens can be used for open radical retropubic prostatectomy. The aim of this retrospective analysis was to compare the combined general epidural anesthesia and the combined spinal epidural anesthesia with regard to availability, efficacy, side effects, and perioperative time consumption in a high-volume center. METHODS: A retrospective analysis was performed by querying the electronic medical records of 1207 consecutive patients from the database of our online documentation software. All patients underwent open radical retropubic prostatectomy from 01/2008 to 08/2011 and met the study criteria. Linear and multivariate regression analyses were performed to identify differences in parameters such as time consumption in the operating unit, hemodynamic parameters, volume replacement, and catecholamine therapy. RESULTS: 698 (57.8%) patients have been undergoing open radical retropubic prostatectomy under combined spinal epidural anesthesia and 509 (42.2%) patients by combined general epidural anesthesia. Operating unit (p <0.0001) and post-anesthesia care unit stay (p <0.0001) as well as total hospital stay (p <0.0001) were significantly shorter in the combined spinal epidural anesthesia group. In addition, this group had reduced intraoperative volume need (p <0.0001) as well as lower need of catecholamines (p <0.0001). CONCLUSIONS: This retrospective study suggests that the combined spinal epidural anesthesia seems to be a suitable and efficient anesthesia technique for patients undergoing open radical retropubic prostatectomy. This specific approach reduces time in the operation unit and length of hospital stay.
The Biopsychosocial Burden of Prostate Biopsy at the Time of Its Indication, Procedure, and Pathological Report.
Laranja WW, Sanches BCF, Voris BRI … +4 more , Alonso JCC, Simões FA, Rejowski RF, Reis LO
Prostate Cancer · 2019 · PMID 31057971 · Full text
PURPOSE: To explore the burden of prostate biopsy at the time of its indication, procedure, and pathological report in the prostate cancer-screening scenario that is neglected and underestimated in the literature. METHOD...
PURPOSE: To explore the burden of prostate biopsy at the time of its indication, procedure, and pathological report in the prostate cancer-screening scenario that is neglected and underestimated in the literature. METHODS: Prostate biopsy was offered to 47 consecutive patients with prostate-specific antigen (PSA) over 4 ng/dl or suspicious digital rectal examination (DRE) of whom 16 had undergone a biopsy. Comprehensive validated questionnaires at Time 0 (prebiopsy), Time 1 (before diagnosis, 20 days after biopsy), and Time 2 (after diagnosis, 40 days after biopsy) accessed patients' erectile (IIEF-5) and voiding (IPSS) functions, Beck scales measured anxiety (BAI), hopelessness (BHS), and depression (BDI), added to the emotional thermometers including five visual analog scales for distress, anxiety, depression, anger, and need for help. The Mann-Whitney or Friedman tests were obtained among times and studied variables. RESULTS: Prostate biopsy did not significantly impact patients' erectile and voiding functions while a higher Beck anxiety index (BAI) was observed at Time 0 (6.89 ± 6.33) compared to Time 1 (4.83 ± 2.87), =0.0214, and to Time 2 (4.22 ± 4.98), =0.0178. At Time 0, patients that experienced a previous biopsy presented higher distress (3.1 ± 3.0 vs. 1.6 ± 2.3), =0.043, and emotional suffering thermometer scores (2.3 ± 3.3 vs. 0.9 ± 2.4) compared to those undergoing the first biopsy, =0.036. At Time 2, patients with positive biopsies compared with those with negative ones showed no significant difference in outcome scores. The sample power was >90%. CONCLUSIONS: To be considered in patients' counseling and care, the current study supports the hypothesis that the peak burden of prostate biopsy occurs at the time of its indication and might be higher for those experiencing rebiopsy, significantly impacting patients' psychosocial domains. TRIAL APPROVAL: This trial is registered under number NCT03783741.
Interactions between Germline and Somatic Mutated Genes in Aggressive Prostate Cancer.
Mamidi TKK, Wu J, Hicks C
Prostate Cancer · 2019 · PMID 31007957 · Full text
Prostate cancer (PCa) is the most common diagnosed malignancy and the second leading cause of cancer-related deaths among men in the USA. Advances in high-throughput genotyping and next generation sequencing technologies...
Prostate cancer (PCa) is the most common diagnosed malignancy and the second leading cause of cancer-related deaths among men in the USA. Advances in high-throughput genotyping and next generation sequencing technologies have enabled discovery of germline genetic susceptibility variants and somatic mutations acquired during tumor formation. Emerging evidence indicates that germline variations may interact with somatic events in carcinogenesis. However, the possible oncogenic interactions and cooperation between germline and somatic variation and their role in aggressive PCa remain largely unexplored. Here we investigated the possible oncogenic interactions and cooperation between genes containing germline variation from genome-wide association studies (GWAS) and genes containing somatic mutations from tumor genomes of 305 men with aggressive tumors and 52 control samples from The Cancer Genome Atlas (TCGA). Network and pathway analysis were performed to identify molecular networks and biological pathways enriched for germline and somatic mutations. The analysis revealed 90 functionally related genes containing both germline and somatic mutations. Transcriptome analysis revealed a 61-gene signature containing both germline and somatic mutations. Network analysis revealed molecular networks of functionally related genes and biological pathways including P53, STAT3, NKX3-1, KLK3, and Androgen receptor signaling pathways enriched for germline and somatic mutations. The results show that integrative analysis is a powerful approach to uncovering the possible oncogenic interactions and cooperation between germline and somatic mutations and understanding the broader biological context in which they operate in aggressive PCa.
How Accurately Can Prostate Gland Imaging Measure the Prostate Gland Volume? Results of a Systematic Review.
Christie DRH, Sharpley CF
Prostate Cancer · 2019 · PMID 30941221 · Full text
AIM: The measurement of the volume of the prostate gland can have an influence on many clinical decisions. Various imaging methods have been used to measure it. Our aim was to conduct the first systematic review of their...
AIM: The measurement of the volume of the prostate gland can have an influence on many clinical decisions. Various imaging methods have been used to measure it. Our aim was to conduct the first systematic review of their accuracy. METHODS: The literature describing the accuracy of imaging methods for measuring the prostate gland volume was systematically reviewed. Articles were included if they compared volume measurements obtained by medical imaging with a reference volume measurement obtained after removal of the gland by radical prostatectomy. Correlation and concordance statistics were summarised. RESULTS: 28 articles describing 7768 patients were identified. The imaging methods were ultrasound, computed tomography, and magnetic resonance imaging (US, CT, and MRI). Wide variations were noted but most articles about US and CT provided correlation coefficients that lay between 0.70 and 0.90, while those describing MRI seemed slightly more accurate at 0.80-0.96. When concordance was reported, it was similar; over- and underestimation of the prostate were variably reported. Most studies showed evidence of at least moderate bias and the quality of the studies was highly variable. DISCUSSION: The reported correlations were moderate to high in strength indicating that imaging is sufficiently accurate when quantitative measurements of prostate gland volume are required. MRI was slightly more accurate than the other methods.
Incidence of Second Primary Malignancies in Patients with Castration-Resistant Prostate Cancer: An Observational Retrospective Cohort Study in the United States.
Saltus CW, Vassilev ZP, Zong J … +4 more , Calingaert B, Andrews EB, Soriano-Gabarró M, Kaye JA
Prostate Cancer · 2019 · PMID 30886751 · Full text
BACKGROUND: New therapies for castration-resistant prostate cancer (CRPC) may be associated with increased risk of second primary malignancies (SPM). We therefore estimated the population-based incidence of SPM among pat...
BACKGROUND: New therapies for castration-resistant prostate cancer (CRPC) may be associated with increased risk of second primary malignancies (SPM). We therefore estimated the population-based incidence of SPM among patients with CRPC in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. We also estimated the proportion of men with CRPC with bone metastases and overall survival. METHODS: We conducted a retrospective cohort study of United States (US) men aged ≥ 65 years with CRPC. Cohort entry was from January 1, 2000, to December 31, 2011, with follow-up through December 31, 2013. Castration resistance was defined by treatment with second-line systemic therapy (after surgical or medical castration). SPM were diagnoses of primary cancers (other than prostate) in SEER or Medicare data. RESULTS: Altogether 2,234 patients met eligibility criteria. Most (1,887; 84.5%) had evidence of bone metastases in Medicare claims. SPM occurred in 172 patients (incidence rate 5.9 per 100 person-years; 95% confidence interval [CI], 5.0-6.8; standardized incidence ratio = 3.1, 95% CI, 2.8-3.6, based on SEER incidence rate of all malignancies except prostate cancer among men aged ≥ 65 years). The most common SPM were lung/bronchus (n = 29, 16.9%), urinary bladder (n = 22, 12.8%), and colon/rectum (n = 21, 12.2%). Median survival was 1.2 years (95% CI, 1.1-1.3); 5-year survival was 9% (95% CI, 7-11%). CONCLUSIONS: This study provides the first estimate of SPM risk in older men with CRPC in the US. The incidence rate is approximately threefold higher than the population-based cancer incidence among men without prostate cancer.
The Prognostic PDE4D7 Score in a Diagnostic Biopsy Prostate Cancer Patient Cohort with Longitudinal Biological Outcomes.
van Strijp D, de Witz C, Vos PC … +13 more , den Biezen-Timmermans E, van Brussel A, Wrobel J, Baillie GS, Tennstedt P, Schlomm T, Heitkötter B, Huss S, Bögemann M, Houslay MD, Bangma C, Semjonow A, Hoffmann R
Prostate Cancer · 2018 · PMID 30147955 · Full text
To further validate the prognostic power of the biomarker PDE4D7, we investigated the correlation of PDE4D7 scores adjusted for presurgical clinical variables with longitudinal postsurgical biological outcomes. RNA was...
To further validate the prognostic power of the biomarker PDE4D7, we investigated the correlation of PDE4D7 scores adjusted for presurgical clinical variables with longitudinal postsurgical biological outcomes. RNA was extracted from biopsy punches of resected tumors (550 patients; RP cohort) and diagnostic needle biopsies (168 patients; DB cohort). Cox regression and survival were applied to correlate PDE4D7 scores with patient outcomes. Logistic regression was used to combine the clinical CAPRA score with PDE4D7. In univariate analysis, the PDE4D7 score was significantly associated with PSA recurrence after prostatectomy in both studied patient cohorts' analysis (HR 0.53; 95% CI 0.41-0.67; p<1.0E-04 and HR 0.47; 95% CI 0.33-0.65; p<1.0E-04, respectively). After adjustment for the presurgical clinical variables preoperative PSA, PSA density, biopsy Gleason, clinical stage, percentage tumor in the biopsy (data only available for RP cohort), and percentage of positive biopsies, the HR was 0.49 (95% CI 0.38-0.64; p<1.0E-04) and 0.43 (95% CI 0.29-0.63; p<1.0E-04), respectively. The addition of the PDE4D7 to the clinical CAPRA score increased the AUC by 5% over the CAPRA score alone (0.82 versus 0.77; p=0.004). This combination model stratified 14.6% patients of the DB cohort to no risk of biochemical relapse (NPV 100%) over a follow-up period of up to 15 years. The PDE4D7 score provides independent risk information for pretreatment risk stratification. Combining CAPRA with PDE4D7 scores significantly improved the clinical risk stratification before surgery.
Local Treatment of Metastatic Prostate Cancer: What is the Evidence So Far?
Leonel Almeida P, Jorge Pereira B
Prostate Cancer · 2018 · PMID 29755791 · Full text
BACKGROUND: Advances in technological, laboratorial, and imaging studies and new treatments available in the last decades significantly improved prostate cancer survival rates. However, this did not occur in metastatic p...
BACKGROUND: Advances in technological, laboratorial, and imaging studies and new treatments available in the last decades significantly improved prostate cancer survival rates. However, this did not occur in metastatic prostate cancer (mPCa) at diagnosis which, in young and fit patients, will become invariably resistant to the established treatments. Progression will lead to an impairment in patients' quality of life and disease-related death. METHODS: The authors intend to perform a literature review of the advantages of primary treatment of mPCa. Articles were retrieved and filtered for relevance from PubMed, SciELO, and ScienceDirect until March 2017. RESULTS: Primary treatment is currently indicated only in cases of nonmetastatic PCa. Nonetheless, there might be some benefits in doing local treatment in mPCa in order to control local disease, prevent new metastasis, and improve the efficacy of chemotherapy and hormonotherapy with similar complications rate when compared to locally confined cancer. Independent factors that have a negative influence are age above 70 years, cT4 stage or high-grade disease, PSA ≥ 20 ng/ml, and pelvic lymphadenopathies. The presence of 3 or more of these factors conditions CSS and OS is the same between patients who performed local treatment and those who did not. Metastasis degree and location number can also influence outcome. Meanwhile, patients with visceral metastases have worse results. CONCLUSIONS: There is growing evidence supporting local treatment in cases of metastatic prostate cancer at diagnosis in the context of a multimodal approach. However, it should be kept in mind that most of the existing studies are retrospective and it would be important to make consistent prospective studies with well-defined patient selection criteria in order to sustain the existing data and understand the main indications to select patients and perform primary treatment in mPCa.
Efficacy of Abiraterone and Enzalutamide in Pre- and Postdocetaxel Castration-Resistant Prostate Cancer: A Trial-Level Meta-Analysis.
Fang M, Nakazawa M, Antonarakis ES … +1 more , Li C
Prostate Cancer · 2017 · PMID 29359049 · Full text
We examined the comparative efficacies of first-line abiraterone and enzalutamide in pre- and postdocetaxel settings in castration-resistant prostate cancer (CRPC) through a trial level meta-analysis. A mixed method appr...
We examined the comparative efficacies of first-line abiraterone and enzalutamide in pre- and postdocetaxel settings in castration-resistant prostate cancer (CRPC) through a trial level meta-analysis. A mixed method approach was applied to 19 unique studies containing 17 median overall survival (OS) estimates and 13 median radiographic progression-free survival (PFS) estimates. We employed a random-effects meta-analysis to compare efficacies of abiraterone and enzalutamide with respect to OS and PFS. In the predocetaxel setting, enzalutamide use was associated with an increase in median OS of 5.9 months ( < 0.001), hazard ratio (HR) = 0.81, and an increase in median PFS of 8.3 months ( < 0.001), HR = 0.47 compared to abiraterone. The advantage of enzalutamide improved after adjusting for baseline Gleason score to 19.5 months ( < 0.001) and 14.6 months ( < 0.001) in median OS and PFS, respectively. In the postdocetaxel setting, the advantage of enzalutamide use was nominally significant for median PFS (1.2 months = 0.02 without adjustment and 2.2 months and = 0.0007 after adjustment); there was no significant difference in median OS between the two agents. The results from this comprehensive meta-analysis suggest a survival advantage with the use of first-line enzalutamide over abiraterone in CRPC and highlight the need for prospective clinical trials.
Biomarkers of Prostatic Cancer: An Attempt to Categorize Patients into Prostatic Carcinoma, Benign Prostatic Hyperplasia, or Prostatitis Based on Serum Prostate Specific Antigen, Prostatic Acid Phosphatase, Calcium, and Phosphorus.
Sarwar S, Adil MA, Nyamath P … +1 more , Ishaq M
Prostate Cancer · 2017 · PMID 28168057 · Full text
Prostatitis, BPH, and P.Ca are the most frequent pathologies of the prostate gland that are responsible for morbidity in men. Raised levels of PSA are seen in different pathological conditions involving the prostate. PAP...
Prostatitis, BPH, and P.Ca are the most frequent pathologies of the prostate gland that are responsible for morbidity in men. Raised levels of PSA are seen in different pathological conditions involving the prostate. PAP levels are altered in inflammatory or infectious or abnormal growth of the prostate tissue. Serum calcium and phosphorus levels were also found to be altered in prostate cancer and BPH. The present study was carried out to study the levels of PSA, PAP, calcium, and phosphorus in serum of patients with Prostatitis, BPH, or P.Ca and also to evaluate the relationship between them. Males in the age group of 50-85 years with LUTS disease symptoms and with PSA levels more than 4 ng/mL were included. A total of 114 patients were analyzed including 30 controls. Prostatitis in 35.7% of cases, BPH in 35.7% of the cases, and P.Ca in 28.57% of the cases were observed. Thus, the nonmalignant cases constitute a majority. PSA, a marker specific for prostatic conditions, was significantly high in all the diseases compared to controls. A rise in serum PSA and PAP indicates prostatitis or, in combination with these two tests, decreased serum calcium shows advanced disease.
Analysis of Argonaute Complex Bound mRNAs in DU145 Prostate Carcinoma Cells Reveals New miRNA Target Genes.
Szczyrba J, Jung V, Beitzinger M … +12 more , Nolte E, Wach S, Hart M, Sapich S, Wiesehöfer M, Taubert H, Wennemuth G, Eichner N, Stempfl T, Wullich B, Meister G, Grässer FA
Prostate Cancer · 2017 · PMID 28163933 · Full text
Posttranscriptional gene regulation by microRNAs (miRNAs) contributes to the induction and maintenance of prostate carcinoma (PCa). To identify mRNAs enriched or removed from Ago2-containing RISC complexes, these complex...
Posttranscriptional gene regulation by microRNAs (miRNAs) contributes to the induction and maintenance of prostate carcinoma (PCa). To identify mRNAs enriched or removed from Ago2-containing RISC complexes, these complexes were immunoprecipitated from normal prostate fibroblasts (PNFs) and the PCa line DU145 and the bound mRNAs were quantified by microarray. The analysis of Ago complexes derived from PNFs or DU145 confirmed the enrichment or depletion of a variety of mRNAs already known from the literature to be deregulated. Novel potential targets were analyzed by luciferase assays with miRNAs known to be deregulated in PCa. We demonstrate that the mRNAs of the death effector domain-containing protein (DEDD), the tumor necrosis factor receptor superfamily, member 10b protein (TNFRSF10B), the tumor protein p53 inducible nuclear protein 1 (TP53INP1), and the secreted protein, acidic, cysteine-rich (SPARC; osteonectin) are regulated by miRNAs miR-148a, miR-20a, miR-24, and miR-29a/b, respectively. Therefore, these miRNAs represent potential targets for therapy. Surprisingly, overexpression of miR-24 induced focus formation and proliferation of DU145 cells, while miR-29b reduced proliferation. The study confirms genes deregulated in PCa by virtue of their presence/absence in the Ago2-complex. In conjunction with the already published miRNA profiles of PCa, the data can be used to identify miRNA-regulated mRNAs.
Influence of In Utero Maternal and Neonate Factors on Cord Blood Leukocyte Telomere Length: Clues to the Racial Disparity in Prostate Cancer?
Weber KA, Heaphy CM, Rohrmann S … +5 more , Gonzalez B, Bienstock JL, Agurs-Collins T, Platz EA, Meeker AK
Prostate Cancer · 2016 · PMID 28070423 · Full text
. Modifiable factors in adulthood that explain the racial disparity in prostate cancer have not been identified. Because racial differences in utero that may account for this disparity are understudied, we investigated t...
. Modifiable factors in adulthood that explain the racial disparity in prostate cancer have not been identified. Because racial differences in utero that may account for this disparity are understudied, we investigated the association of maternal and neonate factors with cord blood telomere length, as a cumulative marker of cell proliferation and oxidative damage, by race. Further, we evaluated whether cord blood telomere length differs by race. . We measured venous umbilical cord blood leukocyte relative telomere length by qPCR in 38 black and 38 white full-term male neonates. Using linear regression, we estimated geometric mean relative telomere length and tested for differences by race. . Black mothers were younger and had higher parity and black neonates had lower birth and placental weights. These factors were not associated with relative telomere length, even after adjusting for or stratifying by race. Relative telomere length in black (2.72) and white (2.73) neonates did not differ, even after adjusting for maternal or neonate factors (all > 0.9). . Maternal and neonate factors were not associated with cord blood telomere length, and telomere length did not differ by race. These findings suggest that telomere length at birth does not explain the prostate cancer racial disparity.
Prostate Cancer: Epigenetic Alterations, Risk Factors, and Therapy.
Kgatle MM, Kalla AA, Islam MM … +2 more , Sathekge M, Moorad R
Prostate Cancer · 2016 · PMID 27891254 · Full text
Prostate cancer (PCa) is the most prevalent urological cancer that affects aging men in South Africa, and mechanisms underlying prostate tumorigenesis remain elusive. Research advancements in the field of PCa and epigene...
Prostate cancer (PCa) is the most prevalent urological cancer that affects aging men in South Africa, and mechanisms underlying prostate tumorigenesis remain elusive. Research advancements in the field of PCa and epigenetics have allowed for the identification of specific alterations that occur beyond genetics but are still critically important in the pathogenesis of tumorigenesis. Anomalous epigenetic changes associated with PCa include histone modifications, DNA methylation, and noncoding miRNA. These mechanisms regulate and silence hundreds of target genes including some which are key components of cellular signalling pathways that, when perturbed, promote tumorigenesis. Elucidation of mechanisms underlying epigenetic alterations and the manner in which these mechanisms interact in regulating gene transcription in PCa are an unmet necessity that may lead to novel chemotherapeutic approaches. This will, therefore, aid in developing combination therapies that will target multiple epigenetic pathways, which can be used in conjunction with the current conventional PCa treatment.
Advances in Radiotherapy for Prostate Cancer Treatment.
Podder T, Song D, Showalter T … +1 more , Beaulieu L
Prostate Cancer · 2016 · PMID 27525121 · Full text
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