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Screening for Prostate Cancer

Raised levels of prostate-specific antigen (PSA) are a common symptom of prostate cancer, however, it can be caused by other conditions too. Routinely screening of all men to check their levels of PSA is a controversial subject across the international medical community, healthcare providers and advocacy groups. This is because there are many risks (including invasive tests, 'false positives', unnecessary treatment and side effects) as well as potential benefits (earlier detection of disease when it is still curable), and the PSA test does not differentiate between slow growing tumours which may never need treatment and more aggressive prostate cancer. Research into better tests is needed.

Current policies vary between different countries. Some advocates recommend all men over 50 have an annual PSA test, many countries recommend against regular mass screening, but increasingly UK and recent US recommendations are for PSA testing to be a individual's decision to make an informed choice. It is complex and best discussed with your doctor.

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Information for Patients and the Public
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Prostate Cancer
Cancer Screening and Early Detection

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  • PubMed search for publications about Prostate Cancer Screening / PSA test - Limit search to: [Reviews]

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    MeSH term: Prostatic Neoplasms
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Chen JF, Lu YT, Cheng S, et al.
Circulating tumor cells in prostate cancer: beyond enumeration.
Clin Adv Hematol Oncol. 2017; 15(1):63-73 [PubMed] Related Publications
Circulating tumor cells (CTCs) are a population of rare cancer cells that have detached from the primary tumor and/or metastatic lesions and entered the peripheral circulation. Enumeration of CTCs has demonstrated value as a prognostic biomarker, and newer studies have pointed to information beyond enumeration that is of critical importance in prostate cancer. Technologic advances that permit examination of the morphology, function, and molecular content of CTCs have made it possible to measure these factors as part of liquid biopsy. These advances provide a way to study tumor evolution and the development of resistance to therapy. Recent breakthroughs have created new applications for CTCs that will affect the care of patients with prostate cancer.

Schreiber D, Safdieh J, Becker DJ, Schwartz D
Patterns of care and survival outcomes of palliative radiation for prostate cancer with bone metastases: comparison of ≤5 fractions to ≥10 fractions.
Ann Palliat Med. 2017; 6(1):55-65 [PubMed] Related Publications
BACKGROUND: To review the palliative radiation fractionation regimens, trends and survival of men within the National Cancer Database (NCDB) diagnosed with prostate cancer and bony metastases.
METHODS: A total of 3,871 patients from the NCDB were included in the analysis (patients treated from 2004-2012). The following fractionation regimens were analyzed [8 Gy × 1, 4 Gy × 5 (short course radiation therapy)], were compared to 3 Gy × 10, 2.50 Gy × 14-15 and 2 Gy × 20-30 (long course radiation therapy). Descriptive statistics, multivariable logistic regression and multivariable cox regression analysis were utilized to assess the data.
RESULTS: Longer fractionation schemes were used for 91.7% of patients. Treatment at an academic center (OR, 2.93), increasing distance from treatment center (OR, 1.48-1.59), treatment to the ribs (OR, 2.47), and year of diagnosis 2009 or later (OR, 2.31-3.26) were associated with an increased likelihood of receiving short course radiation, while treatment to the spine (OR, 0.34) was associated with a decreased likelihood of short course radiation. On multivariable analysis, longer course of radiation was associated with increased overall survival (HR =0.66; 95% CI: 0.56-0.78, P<0.001.). However, on landmark analysis this difference disappeared once limiting the survival analysis to men who survived ≥18 months [HR =0.83; 95% CI: 0.62-1.11, P=0.21].
CONCLUSIONS: Fractionation schemes of ≥10 treatments remain the dominant palliative course of radiation therapy offered for metastatic prostate cancer. However, utilization of ≤5 fractions is slowly increasing, particularly at academic centers.

Meng P, Dong QC, Tan GG, et al.
Anti-tumor effects of a recombinant anti-prostate specific membrane antigen immunotoxin against prostate cancer cells.
BMC Urol. 2017; 17(1):14 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: To evaluate anti-prostate cancer effects of a chimeric tumor-targeted killer protein.
METHODS: We established a novel fusion gene, immunocasp-3, composed of NH2-terminal leader sequence fused with an anti-prostate-specific membrane antigen (PSMA) antibody (J591), the furin cleavage sequences of diphtheria toxin (Fdt), and the reverse coding sequences of the large and small subunits of caspase-3 (revcaspase-3). The expressing level of the immunocasp-3 gene was evaluated by using the reverse transcription-PCR (RT-PCR) and western blot analysis. Cell viability assay and cytotoxicity assay were used to evaluate its anti-tumor effects in vitro. Apoptosis was confirmed by electron microscopy and Annexin V-FITC staining. The antitumor effects of immunocasp-3 were assessed in nude mice xenograft models containing PSMA-overexpressing LNCaP cells.
RESULTS: This study shows that the immunocasp-3 proteins selectively recognized and induced apoptotic death in PSMA-overexpressing LNCaP cells in vitro, where apoptotic cells were present in 15.3% of the cells transfected with the immunocasp-3 expression vector at 48 h after the transfection, in contrast to 5.5% in the control cells. Moreover, LNCaP cells were significantly killed under the condition of the co-culture of the immunocasp-3-secreting Jurkat cells and more than 50% of the LNCaP cells died when the two cell lines were co-cultured within 5 days. In addition, The expression of immunocasp-3 also significantly suppressed tumor growth and greatly prolonged the animal survival rate in vivo.
CONCLUSION: A novel fusion gene, immunocasp-3, may represent a viable approach to treating PSMA-positive prostate cancer.

Messina CS, Weiher H, Schmidt-Wolf IG
Targeting Prostate Cancer with a Combination of WNT Inhibitors and a Bi-functional Peptide.
Anticancer Res. 2017; 37(2):555-559 [PubMed] Related Publications
BACKGROUND/AIM: Prostate cancer is the most common cancer in the Western world. A bi-functional peptide was combined with wingless-related integration site (WNT) inhibitors to determine if there is an additive therapeutic effect when they are used against prostate cancer, since their efficacy has already been proven when used alone.
MATERIALS AND METHODS: A bi-functional peptide (TP-LYT) was designed with a target domain (LTVSPWY) and a lytic domain (KLAKLAK)2, and a second peptide with the same lytic domain but a random sequence instead of the target domain was used as a negative control. Two different WNT inhibitors were used, ethacrynic acid and ciclopiroxolamine. They were tested on prostate cancer cells using the WST-8 assay.
RESULTS: A synergistic effect of peptides and WNT inhibitors was demonstrated, increasing the toxicity against cancer cells.
CONCLUSION: Our findings potentially allow safer treatment since lower concentrations of WNT inhibitors can be used in combination with this bi-functional peptide.

Lertsuwan K, Peters W, Johnson L, et al.
Purinergic Receptor Expression and Cellular Responses to Purinergic Agonists in Human Prostate Cancer Cells.
Anticancer Res. 2017; 37(2):529-537 [PubMed] Related Publications
BACKGROUND: Anticancer activity of extracellular nucleotides has been investigated in many types of cancer. Herein, the effects of extracellular nucleotides and the receptor profile for these nucleotides on prostate cancer (PCa) were elaborated.
MATERIALS AND METHODS: PCa cell lines representing different stages of PCa were used. The effects of ATP and adenosine on PCa growth and migration on different extracellular matrix proteins were examined by MTT and wound-healing assays. Purinergic receptor profiling was carried out by reverse transcription-polymerase chain reaction (RT-PCR).
RESULTS: A growth-inhibitory effect of ATP and adenosine was observed on all PCa cell lines tested. Several ATP-recognized P2 receptors and adenosine receptors were commonly expressed in PCa cell lines. Neither ATP nor adenosine had any significant effect on PCa migration.
CONCLUSION: ATP and adenosine had an antiproliferative effect on PCa cells without affecting their motility, indicating their potential as a novel therapy for PCa.

Ablin RJ, Owen S, Jiang WG
Prostate Transglutaminase (TGase-4) Induces Epithelial-to-Mesenchymal Transition in Prostate Cancer Cells.
Anticancer Res. 2017; 37(2):481-487 [PubMed] Related Publications
More men die with prostate cancer (PCa) than from it. However, once PCa is no longer organ-confined, it is associated with significant mortality. Epithelial-to-mesenchymal transition (EMT) is one mechanism facilitating progression in cancer. Our studies of transglutaminase-4 (TGase-4), a member of the TGase family, expressed in the prostate gland, have implicated it in the regulation of the invasive properties of PCa. The present study investigated the role of TGase-4 on EMT of PCa cells.
MATERIALS AND METHODS: A panel of PCa cell lines: CA-HPV-10, PZ-HPV-7, PC-3 and DU-145 were used. An anti-TGase-4 transgene was constructed to eliminate the expression of TGase-4 in CA-HPV-10 (positive for TGase-4). An expression construct for human TGase-4 was used to transfect PCa cells negative for TGase-4. The pattern of E-cadherin, N-cadherin and vimentin in these cells were evaluated using immunofluorescent staining. Cell motility was assessed using scratch wounding and ekectric cell-substrate impedance sensing (ECIS) assays.
RESULTS: Treatment of PZ-HPV-7 and CA-HPV-10 cells with rhTGase-4 resulted in a significant increase in cell migration (1,407.9 Ω±6.4 Ω vs. 1,691.2 Ω±8.3 Ω in non-treated and rhTGase-4 treated cells, respectively, p<0.01). Cells strongly expressing E-cadherin showed substantial changes of E-cadherin staining in that, after treatment with TGase-4, the intercellular staining of E-cadherin was diminished. Concomitantly, there was acquisition of N-cadherin in TGase-4-treated cells. Elimination of TGase-4 from CA-HPV-10 cells significantly decreased cell motility (128.1 Ω±107.4 Ω vs. 31.7 Ω±26.2 Ω, in CA-HPV-10 control and CA-HPV-10/TGase-4 knockout cells). Knocking- out TGase-4 from CA-HPV-10 cells also resulted in substantial loss of N-cadherin in the cells.
CONCLUSION: TGase-4 resulted in loss of E-cadherin/acquisition of N-cadherin and cell migration indicating it is a keen regulator of EMT in prostate epithelia-derived cancer cells. In concert with its other properties involved in disease progression, the present observations suggest TGase-4 as a prospective marker of disease progression.

Fandella A, Scattoni V, Galosi A, et al.
Italian Prostate Biopsies Group: 2016 Updated Guidelines Insights.
Anticancer Res. 2017; 37(2):413-424 [PubMed] Related Publications
AIM: To present a summary of the updated guidelines of the Italian Prostate Biopsies Group following the best recent evidence of the literature.
MATERIALS AND METHODS: A systematic review of the new data emerging from 2012-2015 was performed by a panel of 14 selected Italian experts in urology, pathology and radiology. The experts collected articles published in the English-language literature by performing a search using Medline, EMBASE and the Cochrane Library database. The articles were evaluated using a systematic weighting and grading of the level of the evidence according to the Grading of Recommendations Assessment, Development and Evaluation framework system.
RESULTS: An initial prostate biopsy is strongly recommended when i) prostate specific antigen (PSA) >10 ng/ml, ii) digital rectal examination is abnormal, iii) multiparametric magnetic resonance imaging (mpMRI) has a Prostate Imaging Reporting and Data System (PIRADS) ≥4, even if it is not recommended. The use of mpMRI is strongly recommended only in patients with previous negative biopsy. At least 12 cores should be taken in each patient plus targeted (fusion or cognitive) biopsies of suspicious area (at mpMRI or transrectal ultrasound). Saturation biopsies are optional in all settings. The optimal strategy for reducing infection complications is still a controversial topic and the instruments to reduce them are actually weak. The adoption of Gleason grade groups in adjunction to the Gleason score when reporting prostate biopsy results is advisable.
CONCLUSION: These updated guidelines and recommendations are intended to assist physicians and patients in the decision-making regarding when and how to perform a prostatic biopsy.

Kinlock BL, Parker LJ, Bowie JV, et al.
High Levels of Medical Mistrust Are Associated With Low Quality of Life Among Black and White Men With Prostate Cancer.
Cancer Control. 2017; 24(1):72-77 [PubMed] Related Publications
BACKGROUND: Medical mistrust is thought to affect health care-based decisions and has been linked to poor health outcomes. The effects of medical mistrust among men with prostate cancer are unknown. Thus, the goal of the current study is to examine the association between medical mistrust and quality of life (QOL) among black and white men with prostate cancer.
METHODS: A total of 877 men (415 black, 462 white) with prostate cancer between the ages of 40 to 81 years who entered the North Carolina Central Cancer Registry during the years 2007 and 2008 were retrospectively recruited. The dependent variable was overall QOL measured by the Functional Assessment of Cancer Therapy-Prostate questionnaire. The primary independent variable was medical mistrust. Multivariate regression analysis was used to assess the association between medical mistrust and overall QOL.
RESULTS: Compared with white men, black men reported a higher level of medical mistrust (black = 2.7, white = 2.4; P < .001) and lower QOL (black = 134.4, white = 139.5; P < 0.001). After controlling for demographical and clinical variables, higher levels of medical mistrust were associated with a reduction in overall QOL among men with prostate cancer (beta = -7.73; standard error = 1.54) CONCLUSIONS: Higher levels of medical mistrust are associated with reduced overall QOL among black and white men with prostate cancer. Interventions targeted to reduce medical mistrust may be effective in increasing the overall QOL of men with prostate cancer.

Cui Z, Liu D, Liu C, Liu G
Serum selenium levels and prostate cancer risk: A MOOSE-compliant meta-analysis.
Medicine (Baltimore). 2017; 96(5):e5944 [PubMed] Free Access to Full Article Related Publications
Some observational studies have shown that elevated serum selenium levels are associated with reduced prostate cancer risk; however, not all published studies support these results. A literature search of PubMed, Embase, Medline, and the Cochrane Library up until September 2016 identified 17 studies suitable for further investigation. A meta-analysis was conducted on these studies to investigate the association between serum selenium levels and subsequent prostate cancer risk. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the overall OR of prostate cancer for the highest versus the lowest levels of serum selenium. We found a pooled OR (95% CI) of 0.76 (0.64, 0.91; P < 0.05). In subgroup analysis, an inverse association between serum selenium levels and prostate cancer risk was found in each of case-control studies, current and former smokers, high-grade cancer cases, advanced cancer cases, and different populations. Such correlations were not found for subgroups containing each of cohort studies, nonsmokers, low-grade cancer cases, and early stage cancer cases. In conclusion, our study suggests an inverse relationship between serum selenium levels and prostate cancer risk. However, further cohort studies and randomized control trials based on non-Western populations are required.

Shipley WU, Seiferheld W, Lukka HR, et al.
Radiation with or without Antiandrogen Therapy in Recurrent Prostate Cancer.
N Engl J Med. 2017; 376(5):417-428 [PubMed] Related Publications
Background Salvage radiation therapy is often necessary in men who have undergone radical prostatectomy and have evidence of prostate-cancer recurrence signaled by a persistently or recurrently elevated prostate-specific antigen (PSA) level. Whether antiandrogen therapy with radiation therapy will further improve cancer control and prolong overall survival is unknown. Methods In a double-blind, placebo-controlled trial conducted from 1998 through 2003, we assigned 760 eligible patients who had undergone prostatectomy with a lymphadenectomy and had disease, as assessed on pathological testing, with a tumor stage of T2 (confined to the prostate but with a positive surgical margin) or T3 (with histologic extension beyond the prostatic capsule), no nodal involvement, and a detectable PSA level of 0.2 to 4.0 ng per milliliter to undergo radiation therapy and receive either antiandrogen therapy (24 months of bicalutamide at a dose of 150 mg daily) or daily placebo tablets during and after radiation therapy. The primary end point was the rate of overall survival. Results The median follow-up among the surviving patients was 13 years. The actuarial rate of overall survival at 12 years was 76.3% in the bicalutamide group, as compared with 71.3% in the placebo group (hazard ratio for death, 0.77; 95% confidence interval, 0.59 to 0.99; P=0.04). The 12-year incidence of death from prostate cancer, as assessed by means of central review, was 5.8% in the bicalutamide group, as compared with 13.4% in the placebo group (P<0.001). The cumulative incidence of metastatic prostate cancer at 12 years was 14.5% in the bicalutamide group, as compared with 23.0% in the placebo group (P=0.005). The incidence of late adverse events associated with radiation therapy was similar in the two groups. Gynecomastia was recorded in 69.7% of the patients in the bicalutamide group, as compared with 10.9% of those in the placebo group (P<0.001). Conclusions The addition of 24 months of antiandrogen therapy with daily bicalutamide to salvage radiation therapy resulted in significantly higher rates of long-term overall survival and lower incidences of metastatic prostate cancer and death from prostate cancer than radiation therapy plus placebo. (Funded by the National Cancer Institute and AstraZeneca; RTOG 9601 ClinicalTrials.gov number, NCT00002874 .).

Fraga A, Ribeiro R, Coelho A, et al.
Genetic polymorphisms in key hypoxia-regulated downstream molecules and phenotypic correlation in prostate cancer.
BMC Urol. 2017; 17(1):12 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: In this study we sought if, in their quest to handle hypoxia, prostate tumors express target hypoxia-associated molecules and their correlation with putative functional genetic polymorphisms.
METHODS: Representative areas of prostate carcinoma (n = 51) and of nodular prostate hyperplasia (n = 20) were analysed for hypoxia-inducible factor 1 alpha (HIF-1α), carbonic anhydrase IX (CAIX), lysyl oxidase (LOX) and vascular endothelial growth factor (VEGFR2) immunohistochemistry expression using a tissue microarray. DNA was isolated from peripheral blood and used to genotype functional polymorphisms at the corresponding genes (HIF1A +1772 C > T, rs11549465; CA9 + 201 A > G; rs2071676; LOX +473 G > A, rs1800449; KDR - 604 T > C, rs2071559).
RESULTS: Immunohistochemistry analyses disclosed predominance of positive CAIX and VEGFR2 expression in epithelial cells of prostate carcinomas compared to nodular prostate hyperplasia (P = 0.043 and P = 0.035, respectively). In addition, the VEGFR2 expression score in prostate epithelial cells was higher in organ-confined and extra prostatic carcinoma compared to nodular prostate hyperplasia (P = 0.031 and P = 0.004, respectively). Notably, for LOX protein the immunoreactivity score was significantly higher in organ-confined carcinomas compared to nodular prostate hyperplasia (P = 0.015). The genotype-phenotype analyses showed higher LOX staining intensity for carriers of the homozygous LOX +473 G-allele (P = 0.011). Still, carriers of the KDR-604 T-allele were more prone to have higher VEGFR2 expression in prostate epithelial cells (P < 0.006).
CONCLUSIONS: Protein expression of hypoxia markers (VEGFR2, CAIX and LOX) on prostate epithelial cells was different between malignant and benign prostate disease. Two genetic polymorphisms (LOX +473 G > A and KDR-604 T > C) were correlated with protein level, accounting for a potential gene-environment effect in the activation of hypoxia-driven pathways in prostate carcinoma. Further research in larger series is warranted to validate present findings.

Sawada N
Risk and preventive factors for prostate cancer in Japan: The Japan Public Health Center-based prospective (JPHC) study.
J Epidemiol. 2017; 27(1):2-7 [PubMed] Free Access to Full Article Related Publications
The incidence of prostate cancer is much lower in Asian than in Western populations. Lifestyle and dietary habits may play a major role in the etiology of this cancer. Given the possibility that risk factors for prostate cancer differ by disease aggressiveness, and the fact that 5-year relative survival rate of localized prostate cancer is 100%, identifying preventive factors against advanced prostate cancer is an important goal. Using data from the Japan Public Health Center-based Prospective Study, the author elucidates various lifestyle risk factors for prostate cancer among Japanese men. The results show that abstinence from alcohol and tobacco might be important factors in the prevention of advanced prostate cancer. Moreover, the isoflavones and green tea intake in the typical Japanese diet may decrease the risk of localized and advanced prostate cancers, respectively.

Shaish H, Taneja SS, Rosenkrantz AB
Prostate MR Imaging: An Update.
Radiol Clin North Am. 2017; 55(2):303-320 [PubMed] Related Publications
Improvements in prostate MR imaging techniques and the introduction of MR imaging-targeted biopsies have had central roles in prostate cancer (PCa) management. The role of MR imaging has progressed from largely staging patients with biopsy-proven PCa to detecting, characterizing, and guiding the biopsy of suspected PCa. These diagnostic advances, combined with improved therapeutic interventions, have led to a more sophisticated and individually tailored approach to patients' unique PCa profile. This review discusses the MR imaging, a standardized reporting scheme, and the role of fusion-targeted prostate biopsy.

Lange R, Heine RT, van Wieringen WN, et al.
Cytotoxic Effects of the Therapeutic Radionuclide Rhenium-188 Combined with Taxanes in Human Prostate Carcinoma Cell Lines.
Cancer Biother Radiopharm. 2017; 32(1):16-23 [PubMed] Related Publications
OBJECTIVE: Rhenium-188-HEDP is an effective radiopharmaceutical for the treatment of painful bone metastases from prostate cancer. The effectiveness of the β-radiation emitted by (188)Re might be enhanced by combination with chemotherapy, using the radiosensitization concept. Therefore, the authors investigated the combined treatment of the taxanes, docetaxel and cabazitaxel, with (188)Re in prostate carcinoma cell lines.
MATERIALS AND METHODS: The cytotoxic effects of single and combined treatment with taxanes and (188)Re were investigated in three human prostate carcinoma cell lines (PC-3, DU 145, and LNCaP), using the colony-forming assay. The half maximal effective concentration (EC50) of all individual agents was determined. The combined treatment was studied at 0.25, 0.5, 1, 2, and 4 times the EC50 of each agent. The interaction was investigated with a regression model.
RESULTS: The survival curves showed dose-dependent cell growth inhibition for both the taxanes and (188)Re. The regression model showed a good capability of explaining the data. It proved additivity in all combination experiments and confirmed a general trend to a slight subadditive effect.
CONCLUSIONS: This proof-of-mechanism study exploring radiosensitization by combining (188)Re and taxanes showed no synergism, but significant additivity. This encourages the design of in vivo studies. Future research should explore the potential added value of concomitant treatment of bone metastases with chemotherapy and (188)Re-HEDP.

Vanneste BG, Van Limbergen EJ, van Lin EN, et al.
Prostate Cancer Radiation Therapy: What Do Clinicians Have to Know?
Biomed Res Int. 2016; 2016:6829875 [PubMed] Free Access to Full Article Related Publications
Radiotherapy (RT) for prostate cancer (PC) has steadily evolved over the last decades, with improving biochemical disease-free survival. Recently population based research also revealed an association between overall survival and doses ≥ 75.6 Gray (Gy) in men with intermediate- and high-risk PC. Examples of improved RT techniques are image-guided RT, intensity-modulated RT, volumetric modulated arc therapy, and stereotactic ablative body RT, which could facilitate further dose escalation. Brachytherapy is an internal form of RT that also developed substantially. New devices such as rectum spacers and balloons have been developed to spare rectal structures. Newer techniques like protons and carbon ions have the intrinsic characteristics maximising the dose on the tumour while minimising the effect on the surrounding healthy tissue, but clinical data are needed for confirmation in randomised phase III trials. Furthermore, it provides an overview of an important discussion issue in PC treatment between urologists and radiation oncologists: the comparison between radical prostatectomy and RT. Current literature reveals that all possible treatment modalities have the same cure rate, but a different toxicity pattern. We recommend proposing the possible different treatment modalities with their own advantages and side-effects to the individual patient. Clinicians and patients should make treatment decisions together (shared decision-making) while using patient decision aids.

Solinas C, Chanzá NM, Awada A, Scartozzi M
The immune infiltrate in prostate, bladder and testicular tumors: An old friend for new challenges.
Cancer Treat Rev. 2017; 53:138-145 [PubMed] Related Publications
In genito-urinary tumors immunotherapy has been administered for a long time: Calmette-Guèrin Bacillus as adjuvant treatment in high risk patients with non muscle invasive urothelial bladder cancer and interleukin-2 and interferon-α in metastatic kidney cancer. The vaccine Sipuleucel-T has been approved by United States Food and Drug Administration for the treatment of castration resistant prostate cancer patients with asymptomatic or minimally symptomatic disease, given the 22% reduction of mortality risk in this group. Recently immunotherapeutic agents targeting inhibitory immune checkpoint molecules lead to improved outcomes and lasting anti-tumor effects in a variety of hematological and solid malignancies, including urogenital tumors. The benefit from these treatments has been observed only in a proportion of subjects, raising a need in optimizing patients' selection for immune checkpoint blockade. The composition and activity of a pre-existing immune infiltrate may aid in identifying ideal candidates to immunotherapy, with possible implications for the clinical management of neoplastic diseases from earlier to later stages.

Tang T, Yang Z, Zhang D, et al.
Clinicopathological study of 9 cases of prostate cancer involving the rectal wall.
Diagn Pathol. 2017; 12(1):8 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Prostate cancer involving the rectal wall is rare and may lead to diagnostic pitfalls.
CASE PRESENTATION: Out of 9504 patients with rectal tumors between January 2003 and January 2015, 9 patients (elderly with a mean age of 74 years) with prostate cancer involving the rectal wall were clinically misdiagnosed with rectal cancer. The lesions were located in the rectum, and included 3 circumferential rectal masses, 1 ulceration lesion, 1 crater-like mass, and 4 protruding lesions. Specimens were acquired using biopsy, fine needle aspiration, or resection. The initial symptoms of these patients included rectal urgency, bowel obstruction, and lower gastrointestinal bleeding. Prostate-related symptoms were not obvious. Histologically, 2 cases showed cancer cell invasion in the mucosa, 1 showed transmural invasion from the mucosa to subserosal soft tissues, and 7 cases had submucosa and muscularis propria involvement. All the 9 cases had muscularis propria involvement. However, there were no intraepithelial neoplasias in the mucosal layer, which is reminiscent of rectal carcinoma. The tumors consisted of small-sized or foamy cells that formed acinus-like, duct-like, and cribriform-like structures. We conducted histological staining and an immunohistochemical analysis for CDX-2, prostate-specific antigen (PSA), P504s, villin, carcinoembryonic antigen, CK-pan, cytokeratin 20, and Ki-67. All tumors were PSA and CK-pan positive, 5 of 9 tumors were P504s-positive, and all tumors were negative for the other markers. All patients underwent standard therapy for prostate cancer after the definitive pathological diagnosis. As of March 31, 2015, 8 patients were alive and 1 had died of prostate cancer 6 months posttreatment.
CONCLUSIONS: Adenocarcinoma appearing in the rectal wall is not always rectal carcinoma. It is necessary to perform a differential diagnosis for prostate cancer in cases of rectal malignant tumors in elderly male patients. Any treatment should be postponed until the final definitive diagnosis is reached.

Huang Y, Zou X, Zhang X, et al.
Magnolin inhibits prostate cancer cell growth in vitro and in vivo.
Biomed Pharmacother. 2017; 87:714-720 [PubMed] Related Publications
BACKGROUND: Magnolin is the most active ingredient in the herb Magnolia fargesii, which has been traditionally used in oriental medicine to treat headaches and nasal congestion. Recent researches demonstrate that Magnolin inhibits cancer cell migration and invasion.
MATERIALS AND METHODS: This study used cell culture and the BALB/c nu/nu mouse xenograft model to investigate whether or not magnolin can inhibit the growth of PC3 and Du145 prostate cancer cells. MTT assay and flow cytometry were performed to estimate the proliferation, cycle, and apoptosis of the cells in vitro. Clone formation assay was also conducted. In the animal study, Ki-67 immunostaining and TUNEL assay were carried out to evaluate cell proliferation and apoptosis, respectively. To elucidate the possible mechanism by which magnolin attenuates prostate cancer cell growth, we estimated the expression levels of Akt/p-Akt, P53, P21, BCL-2, and cleaved Caspase3 by using Western blot 48h after magnolin-treatment of the cells.
RESULTS: Magnolin inhibited the proliferation and viability of the tumor cells by triggering cell cycle arrest via P53/P21 activation and inducing apoptosis in vitro and in vivo. Magnolin downregulated the phosphorylation of Akt protein kinase and upregulated cleaved Caspase3 during anti-proliferation and pro-apoptosis.
CONCLUSION: Magnolin may be a novel medicine for prostate cancer therapy.

Osip'yants AI, Knyazev EN, Galatenko AV, et al.
Changes in the Level of Circulating hsa-miR-297 and hsa-miR-19b-3p miRNA Are Associated with Generalization of Prostate Cancer.
Bull Exp Biol Med. 2017; 162(3):379-382 [PubMed] Related Publications
We performed diagnostic classification of plasma specimens from patients with non-metastatic and metastatic prostate cancer based on pairs of miRNA that have no individual diagnostic significance. Of 230 miRNA detected in plasma specimens, 3 pairs were diagnostically significant. The miRNA pair hsa-miR-19b-3p and hsa-miR-297 demonstrated highest sensitivity and specificity. Among common target genes of these miRNA, CFL2 gene associated with cell mobility was detected.

Günzel K, Cash H, Buckendahl J, et al.
The addition of a sagittal image fusion improves the prostate cancer detection in a sensor-based MRI /ultrasound fusion guided targeted biopsy.
BMC Urol. 2017; 17(1):7 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: To explore the diagnostic benefit of an additional image fusion of the sagittal plane in addition to the standard axial image fusion, using a sensor-based MRI/US fusion platform.
METHODS: During July 2013 and September 2015, 251 patients with at least one suspicious lesion on mpMRI (rated by PI-RADS) were included into the analysis. All patients underwent MRI/US targeted biopsy (TB) in combination with a 10 core systematic prostate biopsy (SB). All biopsies were performed on a sensor-based fusion system. Group A included 162 men who received TB by an axial MRI/US image fusion. Group B comprised 89 men in whom the TB was performed with an additional sagittal image fusion.
RESULTS: The median age in group A was 67 years (IQR 61-72) and in group B 68 years (IQR 60-71). The median PSA level in group A was 8.10 ng/ml (IQR 6.05-14) and in group B 8.59 ng/ml (IQR 5.65-12.32). In group A the proportion of patients with a suspicious digital rectal examination (DRE) (14 vs. 29%, p = 0.007) and the proportion of primary biopsies (33 vs 46%, p = 0.046) were significantly lower. The rate of PI-RADS 3 lesions were overrepresented in group A compared to group B (19 vs. 9%; p = 0.044). Classified according to PI-RADS 3, 4 and 5, the detection rates of TB were 42, 48, 75% in group A and 25, 74, 90% in group B. The rate of PCa with a Gleason score ≥7 missed by TB was 33% (18 cases) in group A and 9% (5 cases) in group B; p-value 0.072. An explorative multivariate binary logistic regression analysis revealed that PI-RADS, a suspicious DRE and performing an additional sagittal image fusion were significant predictors for PCa detection in TB. 9 PCa were only detected by TB with sagittal fusion (sTB) and sTB identified 10 additional clinically significant PCa (Gleason ≥7).
CONCLUSION: Performing an additional sagittal image fusion besides the standard axial fusion appears to improve the accuracy of the sensor-based MRI/US fusion platform.

Hatiboglu G, Popeneciu IV, Deppert M, et al.
Quality of life and functional outcome after infravesical desobstruction and HIFU treatment for localized prostate cancer.
BMC Urol. 2017; 17(1):5 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: To evaluate quality of life, functional and oncological outcome after infravesical desobstruction and HIFU treatment for localized prostate cancer.
METHODS: One hundred thirty-one patients, treated with TURP and HIFU in a single institution were followed up for oncological and functional outcome. Oncological outcome was quantified by biochemical recurrence free survival using the Stuttgart and Phoenix criteria. Quality of life was assessed by usage of standardized QLQ-C30 and QLQ-PR25 questionnaires. In addition, functional questionnaires such as IPSS and IIEF-5 were used. Complications were assessed by the Clavien-Dindo classification.
RESULTS: One hundred thirty-one patients with a mean age of 72.8 years (SD: 6.0) underwent HIFU for prostate cancer (29.0% low risk, 58.8% intermediate risk, 12.2% high risk). PSA nadir was 0.6 ng/ml (SD: 1.2) after a mean of 4.6 months (SD: 5.7). Biochemical recurrence free survival defined by Stuttgart criteria was 73.7%, 84.4% and 62.5% for low-, intermediate- and high-risk patients after 22.2 months. Complications were grouped according to Clavien-Dindo and occurred in 10.7% (grade II) and 11.5% (grade IIIa) of cases. 35.1% of patients needed further treatment for bladder neck stricture. Regarding incontinence, 14.3%, 2.9% and 0% of patients had de novo urinary incontinence grade I°, II° and III° and 3.8% urge incontinence due to HIFU treatment. Patients were asked for the ability to have intercourse: 15.8%, 58.6% and 66.7% of patients after non-, onesided and bothsided nervesparing procedure were able to obtain sufficient erection for intercourse, respectively. Regarding quality of life, mean global health score according to QLQ-C30 was 69.4%.
CONCLUSION: HIFU treatment for localized prostate cancer shows acceptable oncological safety. Quality of life after HIFU is better than in the general population and ranges within those of standard treatment options compared to literature. HIFU seems a safe valuable treatment alternative for patients not suitable for standard treatment.

Feng F, Wu J, Gao Z, et al.
Screening the key microRNAs and transcription factors in prostate cancer based on microRNA functional synergistic relationships.
Medicine (Baltimore). 2017; 96(1):e5679 [PubMed] Free Access to Full Article Related Publications
Prostate cancer (PC) is a common neoplasm, and metastatic PC remains incurable. The study aims to screen key microRNAs (miRNAs) and transcription factors (TFs) involved in PC.The miRNA expression profile dataset (GSE45604) was downloaded from Gene Expression Omnibus database, including 50 PC and 10 normal specimens. Differentially expressed miRNAs (DEmiRNAs) were identified through limma package in R, and DEmiRNA-DEmiRNA co-regulation network was constructed based on the number of co-regulated target genes. Functional enrichment analysis of co-regulated target genes was performed using clusterProfiler package in R, and miRNA interactions sharing at least 1 functional term were used to construct a DEmiRNA-DEmiRNA functional synergistic network (MFSN). Based on Transcriptional Regulatory Element Database, cancer-related TFs which were co-regulated by DEmiRNAs were utilized to construct a DEmiRNA-TF regulation network.A total of 66 DEmiRNAs were identified, including 7 up-regulated miRNAs with 18,642 target genes and 59 down-regulated miRNAs with 130,694 target genes. Then, the DEmiRNA-DEmiRNA co-regulation network was constructed, including 66 DEmiRNAs and 2024 co-regulation relationships. In MFSN, hsa-miR-1184, hsa-miR-1207-5p, and hsa-miR-24 had significant functional synergistic relationships. The DEmiRNA-TF network contained 6 up-regulated DEmiRNAs and 4 of them were highlighted, as hsa-miR-1184, hsa-miR-1207-5p, hsa-miR-182, and hsa-miR-183. In subnetwork of the 4 miRNAs, peroxisome proliferative activated receptor, alpha (PPARA) and cyclic AMP-responsive element modulator (CREM) were the critical regulated TFs.Four up-regulated miRNAs (hsa-miR-1207-5p, hsa-miR-1184, hsa-miR-182, and hsa-miR-183) and 2 TFs (PPARA and CREM) were identified as key regulators in PC progression. The above 4 miRNAs might participate in PC progression by targeting PPARA and CREM.

Noto B, Weckesser M, Buerke B, et al.
Gastrointestinal Stromal Tumor Showing Intense Tracer Uptake on PSMA PET/CT.
Clin Nucl Med. 2017; 42(3):200-202 [PubMed] Related Publications
A 70-year-old man with suspected prostate cancer was referred for Ga-PSMA-HBED-CC PET/CT (short PSMA PET/CT) for staging of tumor extent. Apart from vivid tracer uptake in the prostate gland and osseous metastasis, PSMA PET/CT revealed a large soft tissue mass with calcifications in the left upper abdomen showing intense tracer uptake. Histologic examination revealed the mass to be a gastrointestinal stromal tumor.

Xu W, Chang J, Liu G, et al.
Knockdown of FOXR2 suppresses the tumorigenesis, growth and metastasis of prostate cancer.
Biomed Pharmacother. 2017; 87:471-475 [PubMed] Related Publications
Fork-head box R2 (FOXR2), a member of FOX protein family, was reported to play important roles in the development and progression of cancers. However, the expression and function of FOXR2 in prostate cancer remain unclear. In this study, we investigated the role of FOXR2 in prostate cancer and cancer progression including the molecular mechanism that drives FOXR2-mediated oncogenesis. Our results showed that FOXR2 was overexpressed in prostate cancer cell lines. The in vitro experiments demonstrated that knockdown of FOXR2 significantly repressed the proliferation, migration and invasiveness of prostate cancer cells. Furthermore, the in vivo experiments indicated that knockdown of FOXR2 significantly attenuated prostate cancer growth. Finally, knockdown of FOXR2 significantly down-regulated the protein expression levels of β-catenin, cyclinD1 and c-Myc in DU-145 cells. Taken together, our results demonstrated for the first time that FOXR2 plays a critical role in cell proliferation and invasion, at least in part, through inhibiting the Wnt/β-catenin signaling pathway during prostate cancer progression. Thus, FOXR2 may be an attractive therapeutic target for the treatment of prostate cancer.

Chan S, Zhang L, Rowbottom L, et al.
Effects of circadian rhythms and treatment times on the response of radiotherapy for painful bone metastases.
Ann Palliat Med. 2017; 6(1):14-25 [PubMed] Related Publications
BACKGROUND: Previous studies have observed how the time of radiotherapy delivery can impact toxicities and outcomes. The goal of this study was to determine whether treatment time influenced radiotherapy response for bone metastases.
METHODS: Patients who received radiation treatment to painful bone metastases from January 2000 to December 2010 were included in our analysis. Demographic and treatment information including performance status, primary site, treatment dose and fraction, and response were collected prospectively. Treatment times were extracted from patient medical records. Patients were allocated to 8:00 AM-11:00 AM, 11:01 AM-2:00 PM, or 2:01 PM-5:00 PM cohorts based on their treatment times. To compare treatment response between the three cohorts, the Fisher exact test was used. A two-sided P value of <0.05 was considered statistically significant. Analysis was repeated with males and females separately.
RESULTS: A total of 194 patients were included. The median age was 68 years and 55.5% of patients responded to treatment. The dose and fraction of radiation received differed significantly between treatment cohorts using all allocation methods. Females in the 11:01 AM-2:00 PM cohort exhibited a significantly higher response rate (P=0.02) and differing proportions of response types (P=0.03) compared to the 8:00 AM- 11:00 AM and 2:01 PM-5:00 PM cohorts when allocated using all treatment times. No significant differences in response were seen between cohorts when all patients were analysed together or analysed for males only.
CONCLUSIONS: Treatment time may affect response in female patients receiving radiotherapy for painful bone metastases. Subsequent chronotherapy studies in radiation should investigate these gender differences.

Yi R, Chen B, Duan P, et al.
Sipuleucel-T and Androgen Receptor-Directed Therapy for Castration-Resistant Prostate Cancer: A Meta-Analysis.
J Immunol Res. 2016; 2016:4543861 [PubMed] Free Access to Full Article Related Publications
New treatments, such as sipuleucel-T and androgen receptor- (AR-) directed therapies (enzalutamide (Enz) and abiraterone acetate (AA)), have emerged and been approved for the management of castration-resistant prostate cancer (CRPC). There are still debates over their efficacy and clinical benefits. This meta-analysis aimed to investigate the efficacy and safety of sipuleucel-T and AR-directed therapies in patients with CRPC. RevMan 5.1 was used for pooled analysis and analysis of publication bias. Seven studies were included in the meta-analysis, with three studies in sipuleucel-T (totally 737 patients, 488 patients in treatment group, and 249 patients in placebo group) and four in AR-directed therapies (totally 5,199 patients, 3,015 patients in treatment group, and 2,184 patients in placebo group). Treatment with sipuleucel-T significantly improved overall survival in patients with CRPC and was not associated with increased risk of adverse event of grade ≥3 (p > 0.05). However, treatment with sipuleucel-T did not improve time-to-progression and reduction of prostate-specific antigen (PSA) level ≥50% was not significantly different from that with placebo. AR-directed therapies significantly improved overall survival in patients with CRPC and improved time-to-progression and reduction of PSA level ≥50%. AR-directed therapies did not increase risk of adverse event of grade ≥3 (p > 0.05).

Froehner M, Koch R, Propping S, et al.
Level of education and mortality after radical prostatectomy.
Asian J Androl. 2017 Mar-Apr; 19(2):173-177 [PubMed] Free Access to Full Article Related Publications
Estimating the risk of competing mortality is of importance in men with early prostate cancer to choose the most appropriate way of management and to avoid over- or under-treatment. In this study, we investigated the impact of the level of education in this context. The study sample consisted of 2630 patients with complete data on level of education (college, university degree, master craftsmen, comparable profession, or others), histopathological tumor stage (organ confined or extracapsular), lymph node status (negative or positive), and prostatectomy specimen Gleason score (<7, 7, or 8-10) who underwent radical prostatectomy between 1992 and 2007. Overall, prostate cancer-specific, competing, and second cancer-related mortalities were study endpoints. Cox proportional hazard models for competing risks were used to study combined effects of the variables on these endpoints. A higher level of education was independently associated with decreased overall mortality after radical prostatectomy (hazard ratio [HR]: 0.75, 95% confidence interval [95% CI]: 0.62-0.91, P = 0.0037). The mortality difference was attributable to decreased second cancer mortality (HR: 0.59, 95% CI: 0.40-0.85, P = 0.0052) and noncancer mortality (HR: 0.73, 95% CI: 0.55-0.98, P = 0.0345) but not to differences in prostate cancer-specific mortality (HR: 1.16, 95% CI: 0.79-1.69, P = 0.4536 in the full model). In conclusion, the level of education might serve as an independent prognostic parameter supplementary to age, comorbidity, and smoking status to estimate the risk of competing mortality and to choose optimal treatment for men with early prostate cancer who are candidates for radical prostatectomy.

Lee J, Ryu J, Lee C
Strong cis-acting expression quantitative trait loci for the genes encoding SNHG5 and PEX6.
Medicine (Baltimore). 2016; 95(52):e5793 [PubMed] Free Access to Full Article Related Publications
Expression of quantitative trait loci (eQTLs) for the genes located in human chromosome 6 were examined. Data on RNA expression in lymphoblastoid cells of 373 unrelated Europeans were used to identify eQTLs.Genome-wide analysis resulted in 24,447 nucleotide variants associated with gene expression (P < 2.16 × 10). We found 36variants with P < 10, which were all associated with expression levels of the genes encoding small nucleolar RNA host gene 5 (SNHG5) and peroxisomal biogenesis factor 6 (PEX6). Enhancer eQTLs downstream of theSNHG5 gene might be candidate genetic factors for susceptibility to cancer. This is because nucleotide substitutions (eg, G→T at rs6922) of the enhancer eQTLs may cause low expression of SNHG5 gene, and low expression of snoRNA U50, a product generated from introns of the SNHG5gene, can induce cancer. One presently identified eQTL for the PEX6 gene was rs10948059, which had been associated with prostate cancer from previous association studies. The results imply that variants associated with prostate cancer can be identified through expressional change in the PEX6 gene, but not in the overlapped glycine N-methyltransferase gene which had been considered as a candidate gene.Further studies are required to understand their underlying mechanisms for the strong eQTLs for the SNHG5 and PEX6 genes.

Gao P, Shi C, Zhao L, et al.
Differential diagnosis of prostate cancer and noncancerous tissue in the peripheral zone and central gland using the quantitative parameters of DCE-MRI: A meta-analysis.
Medicine (Baltimore). 2016; 95(52):e5715 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The objective of this meta-analysis was to evaluate the clinical usefulness of K, Kep, and Ve values in the differential diagnosis of prostate cancer (PCa) and noncancerous tissue in the peripheral zone (PZ) and central gland (CG).
METHODS: A search was conducted of the PubMed, MEDLINE, EMBASE, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases from January 2000 to October 2015 using the search terms "prostate cancer," " dynamic contrast-enhanced (DCE)," "magnetic resonance imaging," "K," "Kep," and "Ve." Studies were selected and included according to strict eligibility criteria. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were used to compare K, Kep, and Ve values between PCa and noncancerous tissue.
RESULTS: Fourteen studies representing 484 patients highly suspicious for prostate adenocarcinoma were selected for the meta-analysis. We found that K values measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were significantly higher in PCa tissue than in noncancerous tissue in the PZ (SMD 1.57, 95% CI 0.98-2.16; z = 5.21, P <0.00001) and CG (SMD 1.19, 95% CI 0.46-1.91; z = 3.21, P = 0.001). Kep values measured by DCE-MRI were significantly higher in PCa than in noncancerous tissue in the PZ (SMD 1.41, 95% CI 0.92-1.91; z = 5.59, P < 0.00001) and CG (SMD 1.57, 95% CI 0.69-2.46; z = 3.49, P = 0.0005). Ve values generated by DCE-MRI were slightly higher in PCa than in noncancerous tissue in the PZ (SMD 0.72, 95% CI 0.17-1.27; z = 2.58, P = 0.010), but sensitivity analysis found that the Ve value was unstable for differentiation between PCa and noncancerous PZ tissue. However, there was no significant difference in the Ve value between PCa and noncancerous CG tissue (SMD -0.29, 95% CI -1.18, 0.59; z = 0.65, P = 0.51).
CONCLUSION: Our meta-analysis shows that K and Kep were the most reliable parameters for differentiating PCa from noncancerous tissue and were critical for evaluation of the internal structure of cancer. The Ve value was not helpful for distinguishing PCa from noncancerous CG tissue; its ability to distinguish between PCa and noncancerous PZ tissue remains uncertain.

Chan M, Hsiao E, Turner J
Cerebellar Metastases From Prostate Cancer on 68Ga-PSMA PET/CT.
Clin Nucl Med. 2017; 42(3):193-194 [PubMed] Related Publications
Ga prostate-specific membrane antigen PET/CT is increasingly used to evaluate extent of disease in prostate carcinoma. Parenchymal brain metastases originating from prostate cancer have highly variable imaging appearance. We present a 77-year-old man with cerebellar metastasis from prostate cancer showing focal uptake on prostate-specific membrane antigen PET/CT.

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