Prostate cancer accounts for over a quarter of all cancers in men. The prostate is a small male sex gland located below the bladder, it produces fluid that becomes semen. Prostate cancer occurs mostly in older men, it is rare before the age of 50, and the risk increases with age. There has been an increase in the incidence of prostate cancer since the early 1980's, most likely due to an increased use of screening using the prostate-specific antigen (PSA) test. However, the role as screening for prostate cancer remains controversial. World-wide about 395,000 men are diagnosed with prostate cancer each year.
Founded in 1993, PCF has grown into a global Foundation which has funded hundreds of research studies in over 16 countries. The Website includes detailed information about prostate cancer, research and personal accounts of prostate cancer. Head office in Santa Monica.
NHS Choices Video: An expert explains the symptoms and treatment options available. Phillip Kissi describes his personal experience of being diagnosed with prostate cancer
A national charity set up in 1996, with a mission to increase spending on prostate cancer research and raise awareness of the disease. The Website includes extensive information, details of research, and an online community with over 6,000 members.
Prostate cancer: Essential facts
Oncolex - Oslo University Hospital (Norway) and MD Andersen (USA) Narrated animation describing the prostate and prostate cancer.
APCRC-Q One of two disease-specific, consolidated national prostate cancer research centres. APCRC-Q is an initiative between the Queensland University of Technology and the Princess Alexandra Hospital.
Orchid Formed in 1996, Orchid a UK registered charity focusing on male-specific cancers; prostate, penile and testicular. Orchid provides support and information to people affected by or interested in male cancer through a dedicated medical research programme, education and awareness campaigns and a range of support services.
PCEC A national consortium founded in 1988 promoting early detection, research, education and awareness for prostate cancer and all prostate conditions. The Web site includes details of PCEC awareness programmes, cancer information, articles, and reseach.
A registered charity, founded in 1996, dedicated to reducing the impact of prostate cancer by promoting and funding research, awareness and education programs, and providing evidence-based information and resources, support groups and Prostate Cancer Specialist Nurses.
NHS / Public Health England Introduced in 2002, PCRM provides information to enable men to decide whether or not to have the PSA test based on the available evidence about risks and benefits. After consideration of this information and in discussion with their GPs, men over 50 who choose to have the test may do so free of charge, on the NHS. Screening for Prostate Cancer
SA-PCCOC A multidisciplinary group of health professionals comprising urologists, radiation oncologists, nurses and consumers, who undertake clinical prostate cancer and health services research. The site includes extensive prostate cancer information.
Treatment for advanced prostate cancer explained
Macmillan Cancer Support Oncologist Nick Plowman gives an treatment options for people with advanced prostate cancer.
Us TOO A non-profit education and support network of over 300 support group chapters worldwide, providing men and their families with free information, materials and peer-to-peer support. The organization was founded in 1990 by 5 men with prostate cancer.
PubMed Central search for free-access publications about Prostate Cancer MeSH term: Prostatic Neoplasms US National Library of Medicine PubMed has over 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Constantly updated.
PCEC A national consortium founded in 1988 promoting early detection, research, education and awareness for prostate cancer and all prostate conditions. The Web site includes details of PCEC awareness programmes, cancer information, articles, and reseach.
This list of publications is regularly updated (Source: PubMed).
Shore ND, Sieber P, Schimke L, et al. Comparison of tolerability and adverse events following treatment with two GnRH agonists in patients with advanced prostate cancer. Urol Nurs. 2013 Sep-Oct; 33(5):236-44, 248 [PubMed] Related Publications
This multicenter, randomized, crossover, open-label study (ClinicalTrials.gov identifier: NCT01161563) assessed patients'and clinicians'perceptions of injection site tolerability and adverse events following the intramuscular injection of triptorelin pamoate or subcutaneous injection of leuprolide acetate in 107 male, patients with advanced prostate cancer.
Briganti A, Joniau S, Gandaglia G, et al. Patterns and predictors of early biochemical recurrence after radical prostatectomy and adjuvant radiation therapy in men with pT3N0 prostate cancer: implications for multimodal therapies. Int J Radiat Oncol Biol Phys. 2013; 87(5):960-7 [PubMed] Related Publications
PURPOSE: The aim of our study was to evaluate patterns and predictors of early biochemical recurrence (eBCR) after radical prostatectomy (RP) and adjuvant radiation therapy (aRT) in order to identify which individuals might benefit from additional treatments. METHODS AND MATERIALS: We evaluated 390 patients with pT3N0 prostate cancer (PCa) receiving RP and aRT at 6 European centers between 1993 and 2006. Patients who were free from BCR at <2 years' follow-up were excluded. This resulted in 374 assessable patients. Early BCR was defined as 2 consecutive prostate-specific antigen (PSA) test values >0.2 ng/mL within 2 or 3 years after aRT. Uni- and multivariable Cox regression analyses predicting overall and eBCR after aRT were fitted. Covariates consisted of preoperative PSA results, surgical margins, pathological stage, Gleason score, and aRT dose. RESULTS: Overall, 5- and 8-year BCR-free survival rates were 77.1% and 70.8%, respectively. At a median follow-up of 86 months after aRT, 33 (8.8%) and 55 (14.6%) men experienced BCR within 2 or 3 years after aRT, respectively. In multivariable analyses, Gleason scores of 8 to 10 represented the only independent predictor of eBCR after aRT (all, P≤.01). The risk of BCR was significantly higher in patients with a Gleason score of 8 to 10 disease than in those with Gleason 2 to 6 within 24 months after treatment, after adjusting for all covariates (all, P≤.04). However, given a 24-month BCR free period, the risk of subsequent BCR for men with poorly differentiated disease was equal to that of men with less aggressive disease (all, P≥.3). CONCLUSIONS: High Gleason score represents the only predictor of eBCR after RP and aRT in patients affected by pT3N0 PCa. Given the association between early PSA recurrence, clinical progression, and mortality, these patients might be considered candidates for adjuvant medical therapy and/or prophylactic whole-pelvis radiation therapy in addition to aRT, delivered to the prostatic bed.
Foster R, Meyer J, Iyengar P, et al. Localization accuracy and immobilization effectiveness of a stereotactic body frame for a variety of treatment sites. Int J Radiat Oncol Biol Phys. 2013; 87(5):911-6 [PubMed] Related Publications
PURPOSE: The purpose of this study was to analyze the pretreatment setup errors and intrafraction motion using cone beam computed tomography (CBCT) for stereotactic body radiation therapy patients immobilized and localized with a stereotactic body frame for a variety of treatment sites. METHODS AND MATERIALS: Localization errors were recorded for patients receiving SBRT for 141 lung, 29 liver, 48 prostate, and 45 spine tumors representing 1005 total localization sessions. All patients were treated in a stereotactic body frame with a large custom-molded vacuum pillow. Patients were first localized to the frame using tattoos placed during simulation. Subsequently, the frame was aligned to the room lasers according to the stereotactic coordinates determined from the treatment plan. Every patient received a pretreatment and an intrafraction CBCT. Abdominal compression was used for all liver patients and for approximately 40% of the lung patients to reduce tumor motion due to respiration. RESULTS: The mean ± standard deviation pretreatment setup errors from all localizations were -2.44 ± 3.85, 1.31 ± 5.84, and 0.11 ± 3.76 mm in the anteroposterior, superoinferior, and lateral directions, respectively. The mean pretreatment localization results among all treatment sites were not significantly different (F test, P<.05). For all treatment sites, the mean ± standard deviation intrafraction shifts were 0.33 ± 1.34, 0.15 ± 1.45, and -0.02 ± 1.17 mm in the anteroposterior, superoinferior, and lateral directions, respectively. The mean unidimensional intrafraction shifts were statistically different for several of the comparisons (P<.05) as assessed by the Tukey-Kramer test. CONCLUSIONS: Despite the varied tumor locations, the pretreatment mean localization errors for all sites were found to be consistent among the treatment sites and not significantly different, indicating that the body frame is a suitable immobilization and localization device for a variety of tumor sites. Our pretreatment localization errors and intrafraction shifts compare favorably with those reported in other studies using different types of immobilization devices.
Fraggetta F, Pepe P, Improta G, et al. Prostate needle biopsy: what we do and what should be improved. Anal Quant Cytol Histol. 2013; 35(3):130-8 [PubMed] Related Publications
Prostate cancer (PCa) is the cancer most frequently diagnosed in older men and the second most frequent for incidence of all tumors. With the widespread use of serum prostate-specific antigen (PSA), the detection rate as well as the incidence of localized tumors has been increasing, thus leading to a drop in PCa-related mortality. However, a corresponding estimated rate of overdiagnosis as high as 50% has been reported, and the adverse side effects related to unnecessary treatments make the overall benefit of PSA mass screening unclear. The lower PSA threshold and extended prostate biopsy protocols have led to a marked increase of small, low-grade tumors that will never threaten a patient's survival. Sextant biopsy technique, extended biopsy protocols (12-18 cores) and saturation prostate schemes are already familiar terms, together with quantitative histology in the pathology departments. This brief review will try to focus on what usually is done and what should be improved in prostate needle biopsy in order to answer many critical points such as the clinical implication of different modalities of prostate biopsy (transrectal, transperineal or even targeted), the use of quantitative histology and the importance of the new molecular findings in addition to conventional histological parameters in the era of the active surveillance protocols.
López JI, Angulo JC The ejaculatory ducts and their implications in prostate adenocarcinoma. Anal Quant Cytol Histol. 2013; 35(4):205-9 [PubMed] Related Publications
OBJECTIVE: To describe the histological characteristics of the ejaculatory duct and their importance in prostate adenocarcinoma. STUDY DESIGN: Anatomical dissection of the prostate and seminal vesicles was performed in 20 autopsies of males without clinical evidence of prostatic pathology. Specimens were totally sampled to study the complete route of the ejaculatory ducts within the prostate, focusing specifically on the histological characteristics of the stroma enfolding the ducts. RESULTS: Ejaculatory ducts are covered by a distinct fibrous capsule that includes lymphatics and blood vessels with a specific spatial and architectural arrangement. Although easy to recognize in normal conditions, the positive nuclear immunostaining of epithelial cells with PAX-2 and PAX-8 may be of help to recognize the ejaculatory epithelium in problematic cases. These arteriolymphatic units made of hyalinized arteries and ectatic lymphatic vessels run parallel to the ejaculatory duct along its intraprostatic course and continue outside the prostate gland in the subadventitial tissue of seminal vesicles. CONCLUSION: The ejaculatory ducts have a unique characteristic histology that allows its recognition in transrectal core biopsies. The issue matters in daily practice and may have prognostic implications in prostate adenocarcinoma since the invasion of this structure has been associated with a high percentage of extraprostatic disease.
Mandić S, Sudarević B, Marczi S, et al. Interleukin-6 polymorphism and prostate cancer risk in population of Eastern Croatia. Coll Antropol. 2013; 37(3):907-11 [PubMed] Related Publications
Recent studies suggest that chronic inflammation is crucial in the development and progression of prostate cancer (CaP). Interleukin-6 (IL-6) is a proinflammatory cytokine that plays an important role in intraprostatic inflammation and thus carcinogenesis. The -174G > C polymorphism of IL-6 gene has been associated with high IL-6 producer phenotype and an increased risk for CaP. The aim of this study was to evaluate the association between the mentioned IL-6 polymorphism and CaP risk, as well as to compare the genotype frequency between the different tumour grades of CaP, in population of Eastern Croatia. We analyzed the IL-6 polymorphism in 120 CaP patients and 120 controls with benign prostatic hyperplasia (BPH). CaP patients and BPH controls did not statistically differ in studied IL-6 polymorphism. Furthermore, high IL-6 producer genotypes (GG or GC) were more frequent in controls than in CaP group (86.7% vs 80.8%, respectively, p = 0.147). Also, no statistically significant difference in IL-6 high and low producer genotype frequency was noticed between well, moderately and poorly differentiated tumours. Our results, taken together with other studies on the subject, suggest that IL-6 - 174 single nucleotide polymorphism (SNP) distribution may differ between various ethnic groups and that a single cytokine gene polymorphism has probably just a minor effect on CaP susceptibility. Further studies should be performed to clarify the link between SNPs of different cytokines and the risk for CaP.
Haghighi M, Shah S, Taneja SS, Rosenkrantz AB Prostate cancer: diffusion-weighted imaging versus dynamic-contrast enhanced imaging for tumor localization-a meta-analysis. J Comput Assist Tomogr. 2013 Nov-Dec; 37(6):980-8 [PubMed] Related Publications
PURPOSE: The purpose of this study was to compare the diagnostic performance of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) imaging for prostate cancer (PCa) detection by performing a meta-analysis of studies evaluating these techniques within the same patient cohort. METHODS: Evidence-based online databases were searched for studies reporting the performance of DWI and DCE in PCa detection in the same patient cohorts using histopathology as reference standard and providing sufficient data to construct 2 × 2 contingency tables. Pooled estimates of diagnostic performance were computed across included studies. RESULTS: Of 80 initial studies identified, 5 studies (total of 265 patients and 1730 prostatic regions) met criteria for inclusion in the meta-analysis. Pooled sensitivity was 58.4% (95% confidence interval [CI], 53.5%-63.1%) for DWI and 55.3% (95% CI, 50.4%-60.1%) for DCE. Pooled specificity was 89.0% (95% CI, 87.2%-0.7%) for DWI and 87.9% (95% CI, 86.0%-89.6%) for DCE. At summary receiver-operating-characteristic analysis, area-under-the-curve was 0.810 (0.059) for DWI and 0.786 (0.079) for DCE. Heterogeneity across studies was high for sensitivity and specificity [inconsistency index (I), >90%], although heterogeneity of specificity was substantially improved after excluding an outlier study in terms of diagnostic threshold (I = 0.0%-68.8%). Relative performance of DWI and DCE remained similar after this exclusion CONCLUSIONS: There was a paucity of studies comparing DWI and DCE in the same patient cohorts, and heterogeneity among these studies was substantial. Nevertheless, performance of DWI and DCE was similar across identified studies, with both techniques showing substantially better specificity than sensitivity. Larger studies with uniform methodology are warranted to further understand relative merits of the 2 techniques.
Bonekamp D, Bonekamp S, Mullins JK, et al. Multiparametric magnetic resonance imaging characterization of prostate lesions in the active surveillance population: incremental value of magnetic resonance imaging for prediction of disease reclassification. J Comput Assist Tomogr. 2013 Nov-Dec; 37(6):948-56 [PubMed] Related Publications
OBJECTIVE: This study aimed to characterize prostate lesions by multiparametric magnetic resonance imaging (MRI) in active surveillance (AS) and examine the incremental predictive value of MRI in comparison with clinical parameters for disease reclassification. METHODS: Blinded imaging review of 3-T endorectal mMRI from 50 consecutive men was performed. Multiparametric MRI biomarkers and morphological parameters and the predictive value of a suspicious MR lesion of 10 mm or greater for clinical or histopathologic disease reclassification were assessed. RESULTS: Nine patients were reclassified as AS noneligible during follow-up. Morphological parameters, magnetic resonance spectroscopic imaging, and dynamic contrast-enhanced MRI were associated with disease reclassification. Multiparametric MRI best predicted disease reclassification in patients who did not meet clinical AS enrollment criteria and had a suspicious lesion 10 mm or greater, followed by patients with a suspicious lesion of 10 mm or greater. Not meeting enrollment criteria alone was not a significant predictor of disease reclassification. CONCLUSIONS: Multiparametric MRI demonstrates incremental predictive value when used in combination with clinical AS enrollment criteria and supports the assessment of eligibility for AS.
Graham-Steed T, Uchio E, Wells CK, et al. 'Race' and prostate cancer mortality in equal-access healthcare systems. Am J Med. 2013; 126(12):1084-8 [PubMed] Related Publications
BACKGROUND: Reports suggest worse health-related outcomes among black (vs white) men diagnosed with prostate cancer, but appropriate cause-effect inferences are complicated by the relationship of race and other prognostic factors. METHODS: We searched the literature to find contemporary articles focusing on mortality among black and white men with prostate cancer in equal-access healthcare systems. We also directly assessed the association of race and prostate cancer mortality by conducting an observational cohort analysis of 1270 veterans diagnosed with prostate cancer and followed for 11 to 16 years at 9 medical centers within the Veterans Health Administration. RESULTS: Among 5 reports providing quantitative results for the association of race and mortality among men with prostate cancer in equal-access systems, outcomes were similar for black and white men. Race also was not a prognostic factor in the observational cohort analysis of US veterans, with an adjusted hazard ratio for black (vs white) men and prostate cancer mortality of 0.90 (95% confidence interval, 0.58-1.40; P = .65). CONCLUSIONS: Mortality among black and white patients with prostate cancer is similar in equal-access healthcare systems. Studies that find racial differences in mortality (including cause-specific mortality) among men with prostate cancer may not account fully for socioeconomic and clinical factors.
Murphy G, Haider M, Ghai S, Sreeharsha B The expanding role of MRI in prostate cancer. AJR Am J Roentgenol. 2013; 201(6):1229-38 [PubMed] Related Publications
OBJECTIVE: The purpose of this article is to review the many evolving facets of MRI in the evaluation of prostate cancer. We will discuss the roles of multiparametric MRI, including diffusion-weighted MRI, dynamic contrast-enhanced MRI, and MR spectroscopy, as adjuncts to morphologic T2-weighted imaging in detection, staging, treatment planning, and surveillance of prostate cancer. CONCLUSION: Radiologists need to understand the advantages, limitations, and potential pitfalls of the different sequences to provide optimal assessment of prostate cancer.
Zhao H, Bauzon F, Fu H, et al. Skp2 deletion unmasks a p27 safeguard that blocks tumorigenesis in the absence of pRb and p53 tumor suppressors. Cancer Cell. 2013; 24(5):645-59 [PubMed] Article available free on PMC after 11/11/2014 Related Publications
pRb and p53 are two major tumor suppressors. Here, we found that p53 activates expression of Pirh2 and KPC1, two of the three ubiquitin ligases for p27. Loss of p53 in the absence of Skp2, the third ubiquitin ligase for p27, shrinks the cellular pool of p27 ubiquitin ligases to accumulate p27 protein. In the absence of pRb and p53, p27 was unable to inhibit DNA synthesis in spite of its abundance, but could inhibit division of cells that maintain DNA replication with rereplication. This mechanism blocked pRb/p53 doubly deficient pituitary and prostate tumorigenesis lastingly coexistent with bromodeoxyuridine-labeling neoplastic lesions, revealing an unconventional cancer cell vulnerability when pRb and p53 are inactivated.
Schroeck FR, Kaufman SR, Jacobs BL, et al. The impact of technology diffusion on treatment for prostate cancer. Med Care. 2013; 51(12):1076-84 [PubMed] Related Publications
BACKGROUND: The use of local therapy for prostate cancer may increase because of the perceived advantages of new technologies such as intensity-modulated radiotherapy (IMRT) and robotic prostatectomy. OBJECTIVE: To examine the association of market-level technological capacity with receipt of local therapy. DESIGN: Retrospective cohort. SUBJECTS: Patients with localized prostate cancer who were diagnosed between 2003 and 2007 (n=59,043) from the Surveillance Epidemiology and End Results-Medicare database. MEASURES: We measured the capacity for delivering treatment with new technology as the number of providers offering robotic prostatectomy or IMRT per population in a market (hospital referral region). The association of this measure with receipt of prostatectomy, radiotherapy, or observation was examined with multinomial logistic regression. RESULTS: For each 1000 patients diagnosed with prostate cancer, 174 underwent prostatectomy, 490 radiotherapy, and 336 were observed. Markets with high robotic prostatectomy capacity had higher use of prostatectomy (146 vs. 118 per 1000 men, P=0.008) but a trend toward decreased use of radiotherapy (574 vs. 601 per 1000 men, P=0.068), resulting in a stable rate of local therapy. High versus low IMRT capacity did not significantly impact the use of prostatectomy (129 vs. 129 per 1000 men, P=0.947) and radiotherapy (594 vs. 585 per 1000 men, P=0.579). CONCLUSIONS: Although there was a small shift from radiotherapy to prostatectomy in markets with high robotic prostatectomy capacity, increased capacity for both robotic prostatectomy and IMRT did not change the overall rate of local therapy. Our findings temper concerns that the new technology spurs additional therapy of prostate cancer.
Schultz L, Maluf CE, da Silva RC, et al. Discontinuous foci of cancer in a single core of prostatic biopsy: when it occurs and performance of quantification methods in a private-practice setting. Am J Surg Pathol. 2013; 37(12):1831-6 [PubMed] Related Publications
In addition to clinical data, prostatic biopsy (Bx) reports orient urologists in outlining the patient's treatment options. Discontinuous involvement of a core by multiple foci of cancer is not infrequent; however, there is currently no consensus as to which method of quantification should be the standard. We applied 2 distinct approaches to quantify the length of cancer foci in the Bx and compared the results to prostatectomy (RP) parameters. All patients with matched Bx and RP treated by the same medical team between 2006 and 2010 were consecutively included in the study. Tumor extent in the Bx was estimated by multiple approaches, and the length was measured in millimeters. The subset of cases with discontinuous foci of cancer in a single core was initially reported by adding each foci and ignoring the benign intervening prostatic tissue, which was designated as additive quantification (AQ). Upon slide review, these foci were reassessed as a single focus and measured by linear quantification (LQ). RPs were partially embedded according to the International Society of Urological Pathology recommendations, and the percentage of tumor was evaluated with graphic precision. Mean percentage of the tumor in RP (%RP) and in the Bx were arbitrarily classified as limited (<6%) and nonlimited (≥6%). Bx parameters were then correlated with %RP and margin status. All methods of quantification of the tumor in the Bx obtained excellent correlation with %RP. LQ and AQ diverged in 14/38 patients, with a mean total length of cancer of 5.8 mm more than the length obtained by LQ in the same population, accurately upgrading 6/14 cases to nonlimited. This subset (LQ>AQ) was more often seen in Bx with significantly more positive cores (P=0.003) of predominantly Gleason score 7 and associated with positive surgical margins in RP (P=0.034) independent of %RP (21% vs. 19% in the margin-negative cases). However, in the subset of Bx in which the tumor infiltration was continuous (AQ=AL) positive margins were indeed associated with tumor extent (31% vs. 6% in margin-negative cases). Discontinuous foci of cancer in a single core were most often seen in Bx sampling nonlimited disease, and this event was associated with positive surgical margins. LQ of cancer improved the performance of the Bx in predicting RP tumor extent relative to the traditional millimetric sum. Our findings support the idea that discontinuous foci may represent undersampling of a larger irregular nodule; however, this study is based on routine reports and does not directly access tumor biology.
Stope MB, Bradl J, Peters S, et al. Shortened isoforms of the androgen receptor are regulated by the cytoprotective heat-shock protein HSPB1 and the tumor-suppressive microRNA miR-1 in prostate cancer cells. Anticancer Res. 2013; 33(11):4921-6 [PubMed] Related Publications
BACKGROUND: Shortened, constitutively active androgen receptor (AR) isoforms have been characterized and linked to tumor progression and chemoresistance in prostate cancer (PCa). We examined the regulation of shortened AR isoforms by a newly-identified AR regulatory signaling pathway involving heat-shock protein HSPB1 and microRNA miR-1. MATERIALS AND METHODS: HSPB1 and miR-1 were modulated by overexpression and knock-down approaches utilizing the model PCa system, 22Rv1. Subsequently, AR isoform expression levels were quantified by western blot analysis. RESULTS: HSPB1 was identified as an inducer and miR-1 as an inhibitor of AR variants, with no detectable discrimination between long and short AR isoform regulation. CONCLUSION: In 22Rv1 cells, all AR isoforms were co-regulated by the cytoprotective factor HSPB1 and the tumor suppressor miR-1. Notably, our data provide evidence that HSPB1 inhibition is able to target expression of long as well as of short AR isoforms.
Bilbro J, Mart M, Kyprianou N Therapeutic value of quinazoline-based compounds in prostate cancer. Anticancer Res. 2013; 33(11):4695-700 [PubMed] Related Publications
Certain α1-adrenoreceptor antagonists induce significant apoptosis and impair tumor vascularity without affecting cellular proliferation, effects specific to the quinazoline structure. These anticancer effects have been attributed to both induction of classical apoptosis and reversal of anoikis resistance via disruption of integrin-mediated cell survival pathways. Recent drug optimization efforts have generated several novel compounds with quinazoline-derived chemical structure that exert potent anti-tumor activity via anoikis. Results from pre-clinical and clinical studies implicate a potential value of quinazoline-based analogues in prostate cancer prevention and therapy. A retrospective study of a large patient cohort at our center, revealed that treatment with α1-andrenoreceptor antagonists significantly reduced the risk of developing prostate cancer, indicating a potential chemopreventative mechanism for these FDA-approved agents. In the present review we discuss the current understanding of the signaling mechanisms reversing anoikis resistance by the quinazoline-based compounds in prostate tumors, towards enabling identification of novel therapeutic targets for the treatment of metastatic castration-resistant prostate cancer (CRPC).
Park J, Shin DW, Yun SJ, et al. Cross-cultural application of the Korean version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for patients with prostate cancer - EORTC QLQ-PR25. Oncology. 2013; 85(5):299-305 [PubMed] Related Publications
OBJECTIVE: We evaluated the psychometric properties of the Korean version of the European Organization for Research and Treatment of Cancer QLQ-PR25 when applied to Korean prostate cancer (PC) patients. METHODS: A total of 172 patients who underwent curative radical prostatectomy (RP) with or without adjuvant androgen deprivation therapy were asked to complete the Korean version of the EORTC QLQ-C30 and PR25 questionnaires 3 times (before and 3 and 6 months after RP). Psychometric evaluation of the questionnaire was conducted. RESULTS: Multitrait scaling analysis showed satisfactory construct validity in most scales except for bowel symptoms and hormonal treatment-related symptoms. Internal consistency tested by Cronbach's α coefficient met the 0.70 criterion for the urinary symptom, sexual activity and sexual functioning scales at the all 3 time points. Known-group comparison analyses showed better quality-of-life (QOL) scores in patients with higher performance status, and higher hormonal treatment-related symptom scores in patients on hormonal treatment. Responsiveness to changes was in line with clinical implications over time after RP. CONCLUSIONS: Our results show that the EORTC QLQ-PR25 questionnaire has adequate levels in cross-cultural validity. The Korean version of the EORTC QLQ-PR25 is a generally reliable and robust instrument for the assessment of various QOL aspects that can be self-administered to Korean PC patients undergoing RP.
Araujo JC, Trudel GC, Saad F, et al. Docetaxel and dasatinib or placebo in men with metastatic castration-resistant prostate cancer (READY): a randomised, double-blind phase 3 trial. Lancet Oncol. 2013; 14(13):1307-16 [PubMed] Related Publications
BACKGROUND: Src kinase-mediated interactions between prostate cancer cells and osteoclasts might promote bone metastasis. Dasatinib inhibits tyrosine kinases, including Src kinases. Data suggests that dasatinib kinase inhibition leads to antitumour activity, affects osteoclasts, and has synergy with docetaxel, a first-line chemotherapy for metastatic castration-resistant prostate cancer. We assessed whether dasatinib plus docetaxel in chemotherapy-naive men with metastatic castration-resistant prostate cancer led to greater efficacy than with docetaxel alone. METHODS: In this double-blind, randomised, placebo-controlled phase 3 study, we enrolled men of 18 years or older with chemotherapy-naive, metastatic, castration-resistant prostate cancer, and adequate organ function from 186 centres across 25 countries. Eligible patients were randomly assigned (1:1) via an interactive voice response system to receive docetaxel (75 mg/m(2) intravenously every 3 weeks, plus oral prednisone 5 mg twice daily), plus either dasatinib (100 mg orally once daily) or placebo until disease progression or unacceptable toxicity. Randomisation was stratified by Eastern Cooperative Oncology Group performance status (0-1 vs 2), bisphosphonate use (yes vs no), and urinary N-telopeptide (uNTx) value (<60 μmol/mol creatinine vs ≥60 μmol/mol creatinine). All patients, investigators, and personnel involved in study conduct and data analyses were blinded to treatment allocation. The primary endpoint was overall survival, analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00744497. FINDINGS: Between Oct 30, 2008, and April 11, 2011, 1522 eligible patients were randomly assigned to treatment; 762 patients were assigned to dasatinib and 760 to placebo. At final analysis, median follow-up was 19·0 months (IQR 11·2-25·1) and 914 patients had died. Median overall survival was 21·5 months (95% CI 20·3-22·8) in the dasatinib group and 21·2 months (20·0-23·4) in the placebo group (stratified hazard ratio [HR] 0·99, 95·5% CI 0·87-1·13; p=0·90). The most common grade 3-4 adverse events included diarrhoea (58 [8%] patients in the dasatinib group vs 27 [4%] patients in the placebo group), fatigue (62 [8%] vs 42 [6%]), and asthenia (40 [5%] vs 23 [3%]); grade 3-4 pleural effusions were uncommon (ten [1%] vs three [<1%]). INTERPRETATION: The addition of dasatinib to docetaxel did not improve overall survival for chemotherapy-naive men with metastatic castration-resistant prostate cancer. This study does not support the combination of dasatinib and docetaxel in this population of patients. FUNDING: Bristol-Myers Squibb.
Ryan C, Shore ND, Concepcion R A urologic oncology roundtable discussion: how to choose among the available therapies for the treatment of castration-resistant prostate cancer. Postgrad Med. 2013; 125(6):114-6 [PubMed] Related Publications
Results from a recent survey of 100 urologists and 100 oncologists who treat patients with castration-resistant prostate cancer (CRPC) identified a lack of physician confidence in choosing among the variety of new anticancer therapies available, and incorporating these therapies into their clinical decision-making process. In response to a survey conducted by Urologic Oncology, a physician roundtable discussion was convened and this companion summary article created to provide a knowledge-based perspective for optimizing CRPC treatment and improving communication between urologists and oncologists (http://prostatecancer.urologiconcology.org/). The participating experts described the importance of a documented testosterone level, despite androgen-deprivation therapy, and an increase in prostate-specific antigen level when diagnosing patients with CRPC. Recently published data and personal clinical experience in CRPC management using approved chemotherapeutics, immunotherapies, and oral agents were discussed, as were management of bone metastases and the overall survival improvement in patients undergoing treatment.
Rothschild J, Thompson IM, Concepcion RS, Shore ND Infusion therapy and implantables for the urologist. Urol Clin North Am. 2013; 40(4):591-8 [PubMed] Related Publications
The specialty of urology has historically adapted to the changing health care environment. Urologists have been quick to adopt new technology, new therapeutics, and devices to render state-of-the-art patient care with improved clinical outcomes. The busy urology practice is now in the position to deliver many novel and unique therapies across multiple disease states. As a result, clinicians can provide state-of-the-art care in a clinic setting and potentially reduce the overall costs of health care delivery. This article reviews some of these potential new opportunities available to the practicing urologist.
Grayscale transrectal ultrasonographic prostate biopsy using local anesthesia remains the standard approach to the definitive diagnosis of prostate cancer. Careful patient evaluation and preparation are essential to maximize the results and minimize the complications of the biopsy procedure.
Williams S, Chiong E, Lojanapiwat B, et al. Management of prostate cancer in Asia: resource-stratified guidelines from the Asian Oncology Summit 2013. Lancet Oncol. 2013; 14(12):e524-34 [PubMed] Related Publications
Many local and systemic options for prostate cancer have emerged in recent years, but existing management guidelines do not account for diversity in health resources between different countries. We present recommendations for the management of prostate cancer, stratified according to the extent of resource availability-based on a four-tier system of basic, limited, enhanced, and maximum resources-to enable applicability to Asian countries with differing levels of health-care resources. This statement of recommendations was formulated by a multidisciplinary panel from Asia-Pacific countries, at a consensus session on prostate cancer that was held as part of the 2013 Asian Oncology Summit in Bangkok, Thailand.
Liu C, Wang C, Wang K, et al. SMYD3 as an oncogenic driver in prostate cancer by stimulation of androgen receptor transcription. J Natl Cancer Inst. 2013; 105(22):1719-28 [PubMed] Related Publications
BACKGROUND: Androgen receptor (AR) is critical for prostate tumorigenesis and is frequently overexpressed during prostate cancer (PC) progression. However, few studies have addressed the epigenetic regulation of AR expression. METHODS: We analyzed SMYD3 expression in human PC with Western blot and immunohistochemistry. SMYD3 expression was knocked down using short hairpin RNA (shRNA) or small interfering RNA (siRNA). Cell proliferation, colony formation, and apoptosis analyses and xenograft transplantation were performed to evaluate the impact of SMYD3 depletion on PC cells. AR expression and promoter activity were determined using real-time quantitative polymerase chain reaction, western blot, and luciferase reporter assay. AR promoter association with Sp1, SMYD3, and histone modifications was assessed by chromatin immunoprecipitation. Differences in AR mRNA abundance and promoter activity were analyzed using Wilcoxon signed-rank tests, SMYD3 expression was analyzed using with Mann-Whitney U tests for unpaired samples, and tumor weight was analyzed with Student t test. All statistical tests were two-sided. RESULTS: The upregulation of SMYD3 protein expression was observed in seven of eight prostate tumor specimens, compared with matched normal tissues. Immunohistochemical analysis showed a strong SMYD3 staining in the nuclei of PC tissues in eight of 25 (32%) cases and in the cytoplasm in 23 out of 25 (92%) cases, whereas benign prostate tissue exhibited weak immunostaining. Depletion of SMYD3 by siRNA or shRNA inhibited PC cell proliferation (72 hours relative to 24 hours: control shRNA vs SMYD3 shRNA 1: mean fold change = 2.76 vs 1.68; difference = 1.08; 95% confidence interval = 0.78 to 1.38, P < .001), colony formation, cell migration, invasion, and xenograft tumor formation. Two functional SMYD3-binding motifs were identified in the AR promoter region. CONCLUSIONS: SMYD3 promotes prostate tumorigenesis and mediates epigenetic upregulation of AR expression.
Bianchini D, Omlin A, Pezaro C, et al. First-in-human Phase I study of EZN-4176, a locked nucleic acid antisense oligonucleotide to exon 4 of the androgen receptor mRNA in patients with castration-resistant prostate cancer. Br J Cancer. 2013; 109(10):2579-86 [PubMed] Article available free on PMC after 12/11/2014 Related Publications
BACKGROUND: Prostate cancer remains dependent of androgen receptor (AR) signalling, even after emergence of castration resistance. EZN-4176 is a third-generation antisense oligonucleotide that binds to the hinge region (exon 4) of AR mRNA resulting in full-length AR mRNA degradation and decreased AR protein expression. This Phase I study aimed to evaluate EZN-4176 in men with castration-resistant prostate cancer (CRPC). METHODS: Patients with progressing CRPC were eligible; prior abiraterone and enzalutamide treatment were allowed. EZN-4176 was administered as a weekly (QW) 1-h intravenous infusion. The starting dose was 0.5 mg kg(-1) with a 4-week dose-limiting toxicity (DLT) period and a 3+3 modified Fibonacci dose escalation design. After determination of the DLT for weekly administration, an every 2 weeks schedule was initiated. RESULTS: A total of 22 patients were treated with EZN-4176. At 10 mg kg(-1) QW, two DLTs were observed due to grade 3-4 ALT or AST elevation. No confirmed biochemical or soft tissue responses were observed. Of eight patients with <5 circulating tumour cells at baseline, a conversion to <5 was observed in three (38%) patients. The most common EZN-4176-related toxicities (all grades) were fatigue (59%), reversible abnormalities in liver function tests ALT (41%) and AST (41%) and infusion-related reactions including chills (36%) and pyrexia (14%). CONCLUSION: Activity of EZN-4176 at the doses and schedules explored was minimal. The highest dose of 10 mg kg(-1) QW was associated with significant but reversible transaminase elevation.
Plourde A, Gross A, Jiang Z, Owens CL Patterns in immunohistochemical usage in extended core prostate biopsies: comparisons among genitourinary pathologists and nongenitourinary pathologists. Arch Pathol Lab Med. 2013; 137(11):1630-4 [PubMed] Related Publications
CONTEXT: Immunohistochemical (IHC) stains have known utility in prostate biopsies and are widely used to augment routine staining in difficult cases. Patterns in IHC utilization and differences based on pathologist training and experience is understudied in the peer-reviewed literature. OBJECTIVES: To compare the rates of IHC usage between specialized (genitourinary; [GU]) and nonspecialized (non-GU) pathologists in extended core prostate biopsies (ECPBs) and the effects of diagnosis; and in cancer cases Gleason grade, disease extent, and perineural invasion on the rate. DESIGN: Consecutive ECPBs from 2009-2011 were identified and billing data were used to determine the number of biopsies and IHC stains per case. Diagnoses were mapped and in cancer cases, Gleason grade, extent of disease, and perineural invasion were recorded. Pathologists were classified as GU or non-GU on the basis of training and experience. RESULTS: A total of 618 ECPBs were included in the study. Genitourinary pathologists ordered significantly fewer IHC tests per case and per biopsy than non-GU pathologists. The rate of ordering was most disparate for biopsies of cancerous and benign lesions. For biopsies of cancerous lesions, high-grade cancer, bilateral disease, and perineural invasion decreased the rate of ordering in both groups. In cancer cases, GU pathologists ordered significantly fewer stain tests for highest Gleason grade of 3 + 3 = 6, for patients with focal disease and for patients with multiple positive bilateral cores. The effect of the various predictors on IHC ordering rates was similar in both groups. CONCLUSIONS: Genitourinary pathologists ordered significantly fewer IHC stain tests than non-GU pathologists in ECPBs. Guidelines to define when IHC workup is necessary and not necessary may be helpful to guide workups.
Genes encoding subunits of the SWI/SNF chromatin-remodeling complex constitute, collectively, one of the most frequently mutated targets in cancer. Although mutations in SWI/SNF genes are uncommon in prostate cancer, a new study shows that SChLAP1, a long noncoding RNA frequently expressed in aggressive prostate tumors, drives cancer by directly disrupting SNF5, a core subunit of the SWI/SNF complex.
Thompson J, Lawrentschuk N, Frydenberg M, et al. The role of magnetic resonance imaging in the diagnosis and management of prostate cancer. BJU Int. 2013; 112 Suppl 2:6-20 [PubMed] Related Publications
BACKGROUND: The diagnosis of prostate cancer has long been plagued by the absence of an imaging tool that reliably detects and localises significant tumours. Recent evidence suggests that multi-parametric MRI could improve the accuracy of diagnostic assessment in prostate cancer. This review serves as a background to a recent USANZ position statement. It aims to provide an overview of MRI techniques and to critically review the published literature on the clinical application of MRI in prostate cancer. TECHNICAL ASPECTS: The combination of anatomical (T2-weighted) MRI with at least two of the three functional MRI parameters - which include diffusion-weighted imaging, dynamic contrast-enhanced imaging and spectroscopy - will detect greater than 90% of significant (moderate to high risk) tumours; however MRI is less reliable at detecting tumours that are small (<0.5 cc), low grade (Gleason score 6) or in the transitional zone. The higher anatomical resolution provided by 3-Tesla magnets and endorectal coils may improve the accuracy, particularly in primary tumour staging. SCREENING: The use of mpMRI to determine which men with an elevated PSA should undergo biopsy is currently the subject of two large clinical trials in Australia. MRI should be used with caution in this setting and then only in centres with established uro-radiological expertise and quality control mechanisms in place. There is sufficient evidence to justify using MRI to determine the need for repeat biopsy and to guide areas in which to focus repeat biopsy. IMAGE-DIRECTED BIOPSY: MRI-directed biopsy is an exciting concept supported by promising early results, but none of the three proposed techniques have so far been proven superior to standard biopsy protocols. Further evidence of superior accuracy and core-efficiency over standard biopsy is required, before their costs and complexities in use can be justified. TREATMENT SELECTION AND PLANNING: When used for primary-tumour staging (T-staging), MRI has limited sensitivity for T3 disease, but its specificity of greater than 95% may be useful in men with intermediate-high risk disease to identify those with advanced T3 disease not suitable for nerve sparing or for surgery at all. MRI appears to be of value in planning dosimetry in men undergoing radiotherapy, and in guiding selection for and monitoring on active surveillance.
von Eyben FE, Kangasmäki A, Kiljunen T, Joensuu T Volumetric-modulated arc therapy for a pelvic lymph node metastasis from prostate cancer: a case report. Tumori. 2013 May-Jun; 99(3):e120-3 [PubMed] Related Publications
A 50-year-old patient had an early biochemical recurrence after radical prostatectomy and androgen deprivation therapy and castration. An anti-1-amino-3-[¹⁸F] fluorocyclobutane-1-carboxylic acid positron emission tomography/computed tomography scan showed a single pelvic lymph node metastasis. The patient was given volume-modulated arc therapy with a cumulative dose of 50 Gy for the volume with pelvic lymph nodes and 78 Gy to the boost volume for the lymph node metastasis. He experienced only a transitory mild toxicity from the rectum and the urinary bladder and had a partial remission for 16 months.
Mitchell JM Urologists' use of intensity-modulated radiation therapy for prostate cancer. N Engl J Med. 2013; 369(17):1629-37 [PubMed] Related Publications
BACKGROUND: Some urology groups have integrated intensity-modulated radiation therapy (IMRT), a radiation treatment with a high reimbursement rate, into their practice. This is permitted by the exception for in-office ancillary services in the federal prohibition against self-referral. I examined the association between ownership of IMRT services and use of IMRT to treat prostate cancer. METHODS: Using Medicare claims from 2005 through 2010, I constructed two samples: one comprising 35 self-referring urology groups in private practice and a matched control group comprising 35 non-self-referring urology groups in private practice, and the other comprising non-self-referring urologists employed at 11 National Comprehensive Cancer Network centers matched with 11 self-referring urology groups in private practice. I compared the use of IMRT in the periods before and during ownership and used a difference-in-differences analysis to evaluate changes in IMRT use according to self-referral status. RESULTS: The rate of IMRT use by self-referring urologists in private practice increased from 13.1 to 32.3%, an increase of 19.2 percentage points (P<0.001). Among non-self-referring urologists, the rate of IMRT use increased from 14.3 to 15.6%, an increase of 1.3 percentage points (P=0.05). The unadjusted difference-in-differences effect was 17.9 percentage points (P<0.001). The regression-adjusted increase in IMRT use associated with self-referral was 16.4 percentage points (P<0.001). The rate of IMRT use by urologists working at National Comprehensive Cancer Network centers remained stable at 8.0% but increased by 33.0 percentage points among the 11 matched self-referring urology groups. The regression-adjusted difference-in-differences effect was 29.3 percentage points (P<0.001). CONCLUSIONS: Urologists who acquired ownership of IMRT services increased their use of IMRT substantially more than urologists who did not own such services. Allowing urologists to self-refer for IMRT may contribute to increased use of this expensive therapy. (Funded by the American Society for Radiation Oncology.).
van Rij S, Dowell T, Nacey J PSA screening in New Zealand: total population results and general practitioners' current attitudes and practices. N Z Med J. 2013; 126(1381):27-36 [PubMed] Related Publications
AIMS: Prostate cancer is the second most common cancer among men in New Zealand. Prostate-specific antigen (PSA) as a screening tool for prostate cancer remains controversial. The aim was to determine the rate of PSA screening in New Zealand and to survey general practitioners' utility of PSA and their attitudes towards PSA screening. METHOD: A questionnaire was sent to 1000 general practitioners (GPs). In addition, a non-identifiable prospective audit of all registered New Zealand GPs' laboratory PSA tests was accessed for 2011. RESULTS: Of the 931,923 males older than 40 years, 267,037 had a PSA test performed (28.3%). This percentage peaked in the 65-75 age group (45%). 263 GP questionnaires were completed. 79% of all GPs would initiate discussion of PSA testing. The most common method of testing was at a time of another health need or check-up. CONCLUSION: The incidence of yearly PSA testing in the New Zealand male population over the age of 40 is 28%. GPs provide appropriate information for men to make an informed decision about PSA screening. There is an increasing population of GPs who will not initiate any discussion of PSA testing in their male patients.