Prostate Cancer
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Prostate Cancer

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.

Around 41,000 men are diagnosed with prostate cancer each year in the UK. [Source: Cancer Research UK]

This page shows only UK resources. For a more extensive list of resources from around the world see CancerIndex: Prostate Cancer Information for Patients and the Public
Information for Health Professionals / Researchers
Latest Research Publications
Prostate Cancer Screening

Information Patients and the Public (9 links)

Information for Health Professionals / Researchers (4 links)

  • PubMed search for publications about Prostate Cancer - Limit search to: [Reviews]

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    MeSH term: Prostatic Neoplasms
    International US National Library of Medicine
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Latest Research Publications

Showing publications with corresponding authors from the UK (Source: PubMed).

Kulshrestha RK, Vinjamuri S, England A, et al.
The Role of 18F-Sodium Fluoride PET/CT Bone Scans in the Diagnosis of Metastatic Bone Disease from Breast and Prostate Cancer.
J Nucl Med Technol. 2016; 44(4):217-222 [PubMed] Related Publications
We describe the role of (18)F-sodium fluoride ((18)F-NaF) PET/CT bone scanning in the staging of breast and prostate cancer. (18)F-NaF PET was initially utilized as a bone scanning agent in the 1960s and early 1970s, however, its use was restricted by the then-available γ-cameras. The advent of hybrid PET/CT cameras in the late 1990s has shown a resurgence of interest in its use and role. After a brief introduction, this paper describes the radiopharmaceutical properties, dosimetry, pharmacokinetics, and mechanism of uptake of (18)F-NaF. The performance of (18)F-NaF PET/CT is then compared with that of conventional bone scintigraphy using current evidence from the literature. Strengths and weaknesses of (18)F-NaF PET/CT imaging are highlighted. Clinical examples of improved accuracy of diagnosis and impact on patient management are illustrated. Limitations of (18)F-NaF PET/CT imaging are outlined.

Donovan JL, Hamdy FC, Lane JA, et al.
Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer.
N Engl J Med. 2016; 375(15):1425-1437 [PubMed] Article available free on PMC after 13/04/2017 Related Publications
Background Robust data on patient-reported outcome measures comparing treatments for clinically localized prostate cancer are lacking. We investigated the effects of active monitoring, radical prostatectomy, and radical radiotherapy with hormones on patient-reported outcomes. Methods We compared patient-reported outcomes among 1643 men in the Prostate Testing for Cancer and Treatment (ProtecT) trial who completed questionnaires before diagnosis, at 6 and 12 months after randomization, and annually thereafter. Patients completed validated measures that assessed urinary, bowel, and sexual function and specific effects on quality of life, anxiety and depression, and general health. Cancer-related quality of life was assessed at 5 years. Complete 6-year data were analyzed according to the intention-to-treat principle. Results The rate of questionnaire completion during follow-up was higher than 85% for most measures. Of the three treatments, prostatectomy had the greatest negative effect on sexual function and urinary continence, and although there was some recovery, these outcomes remained worse in the prostatectomy group than in the other groups throughout the trial. The negative effect of radiotherapy on sexual function was greatest at 6 months, but sexual function then recovered somewhat and was stable thereafter; radiotherapy had little effect on urinary continence. Sexual and urinary function declined gradually in the active-monitoring group. Bowel function was worse in the radiotherapy group at 6 months than in the other groups but then recovered somewhat, except for the increasing frequency of bloody stools; bowel function was unchanged in the other groups. Urinary voiding and nocturia were worse in the radiotherapy group at 6 months but then mostly recovered and were similar to the other groups after 12 months. Effects on quality of life mirrored the reported changes in function. No significant differences were observed among the groups in measures of anxiety, depression, or general health-related or cancer-related quality of life. Conclusions In this analysis of patient-reported outcomes after treatment for localized prostate cancer, patterns of severity, recovery, and decline in urinary, bowel, and sexual function and associated quality of life differed among the three groups. (Funded by the U.K. National Institute for Health Research Health Technology Assessment Program; ProtecT Current Controlled Trials number, ISRCTN20141297 ; number, NCT02044172 .).

Hamdy FC, Donovan JL, Lane JA, et al.
10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer.
N Engl J Med. 2016; 375(15):1415-1424 [PubMed] Related Publications
Background The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen (PSA) testing remains uncertain. Methods We compared active monitoring, radical prostatectomy, and external-beam radiotherapy for the treatment of clinically localized prostate cancer. Between 1999 and 2009, a total of 82,429 men 50 to 69 years of age received a PSA test; 2664 received a diagnosis of localized prostate cancer, and 1643 agreed to undergo randomization to active monitoring (545 men), surgery (553), or radiotherapy (545). The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up. Secondary outcomes included the rates of disease progression, metastases, and all-cause deaths. Results There were 17 prostate-cancer-specific deaths overall: 8 in the active-monitoring group (1.5 deaths per 1000 person-years; 95% confidence interval [CI], 0.7 to 3.0), 5 in the surgery group (0.9 per 1000 person-years; 95% CI, 0.4 to 2.2), and 4 in the radiotherapy group (0.7 per 1000 person-years; 95% CI, 0.3 to 2.0); the difference among the groups was not significant (P=0.48 for the overall comparison). In addition, no significant difference was seen among the groups in the number of deaths from any cause (169 deaths overall; P=0.87 for the comparison among the three groups). Metastases developed in more men in the active-monitoring group (33 men; 6.3 events per 1000 person-years; 95% CI, 4.5 to 8.8) than in the surgery group (13 men; 2.4 per 1000 person-years; 95% CI, 1.4 to 4.2) or the radiotherapy group (16 men; 3.0 per 1000 person-years; 95% CI, 1.9 to 4.9) (P=0.004 for the overall comparison). Higher rates of disease progression were seen in the active-monitoring group (112 men; 22.9 events per 1000 person-years; 95% CI, 19.0 to 27.5) than in the surgery group (46 men; 8.9 events per 1000 person-years; 95% CI, 6.7 to 11.9) or the radiotherapy group (46 men; 9.0 events per 1000 person-years; 95% CI, 6.7 to 12.0) (P<0.001 for the overall comparison). Conclusions At a median of 10 years, prostate-cancer-specific mortality was low irrespective of the treatment assigned, with no significant difference among treatments. Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring. (Funded by the National Institute for Health Research; ProtecT Current Controlled Trials number, ISRCTN20141297 ; number, NCT02044172 .).

Beltran H, Antonarakis ES, Morris MJ, Attard G
Emerging Molecular Biomarkers in Advanced Prostate Cancer: Translation to the Clinic.
Am Soc Clin Oncol Educ Book. 2016; 35:131-41 [PubMed] Related Publications
Recent clinical and preclinical studies focused on understanding the molecular landscape of castration-resistant prostate cancer (CRPC) have provided insights into mechanisms of treatment resistance, disease heterogeneity, and potential therapeutic targets. This work has served as a framework for several ongoing clinical studies focused on bringing novel observations into the clinic in the form of tissue, liquid, and imaging biomarkers. Resistance in CRPC typically is driven through reactivation of androgen receptor (AR) signaling, which can occur through AR-activating point mutations, amplification, splice variants (such as AR-V7), or other bypass mechanisms. Detection of AR aberrations in the circulation negatively impacts response to subsequent AR-directed therapies such as abiraterone and enzalutamide. Other potentially clinically relevant alterations in CRPC include defects in DNA damage repair (at either the somatic or germline level) in up to 20% of patients (with implications for PARP1 inhibitor therapy), PI3K/PTEN/Akt pathway activation, WNT signaling pathway alterations, cell cycle gene alterations, and less common but potentially targetable alterations involving RAF and FGFR2. Imaging biomarkers that include those focused on incorporating overexpressed androgen-regulated genes/proteins, such as prostate-specific membrane antigen (PSMA) and dihydrotestosterone (DHT) in combination with CT, can noninvasively identify patterns of AR-driven distribution of CRPC tumor cells, monitor early metastatic lesions, and potentially capture heterogeneity of response to AR-directed therapies and other therapeutics. This article focuses on the current state of clinical biomarker development and future directions for how they might be implemented into the clinic in the near term to improve risk stratification and treatment selection for patients.

Adeloye D, David RA, Aderemi AV, et al.
An Estimate of the Incidence of Prostate Cancer in Africa: A Systematic Review and Meta-Analysis.
PLoS One. 2016; 11(4):e0153496 [PubMed] Article available free on PMC after 13/04/2017 Related Publications
BACKGROUND: Prostate cancer (PCa) is rated the second most common cancer and sixth leading cause of cancer deaths among men globally. Reports show that African men suffer disproportionately from PCa compared to men from other parts of the world. It is still quite difficult to accurately describe the burden of PCa in Africa due to poor cancer registration systems. We systematically reviewed the literature on prostate cancer in Africa and provided a continent-wide incidence rate of PCa based on available data in the region.
METHODS: A systematic literature search of Medline, EMBASE and Global Health from January 1980 to June 2015 was conducted, with additional search of Google Scholar, International Association of Cancer Registries (IACR), International Agency for Research on Cancer (IARC), and WHO African region websites, for studies that estimated incidence rate of PCa in any African location. Having assessed quality and consistency across selected studies, we extracted incidence rates of PCa and conducted a random effects meta-analysis.
RESULTS: Our search returned 9766 records, with 40 studies spreading across 16 African countries meeting our selection criteria. We estimated a pooled PCa incidence rate of 22.0 (95% CI: 19.93-23.97) per 100,000 population, and also reported a median incidence rate of 19.5 per 100,000 population. We observed an increasing trend in PCa incidence with advancing age, and over the main years covered.
CONCLUSION: Effective cancer registration and extensive research are vital to appropriately quantifying PCa burden in Africa. We hope our findings may further assist at identifying relevant gaps, and contribute to improving knowledge, research, and interventions targeted at prostate cancer in Africa.

Salkeld G, Cunich M, Dowie J, et al.
The Role of Personalised Choice in Decision Support: A Randomized Controlled Trial of an Online Decision Aid for Prostate Cancer Screening.
PLoS One. 2016; 11(4):e0152999 [PubMed] Article available free on PMC after 13/04/2017 Related Publications
IMPORTANCE: Decision support tools can assist people to apply population-based evidence on benefits and harms to individual health decisions. A key question is whether "personalising" choice within decisions aids leads to better decision quality.
OBJECTIVE: To assess the effect of personalising the content of a decision aid for prostate cancer screening using the Prostate Specific Antigen (PSA) test.
DESIGN: Randomized controlled trial.
SETTING: Australia.
PARTICIPANTS: 1,970 men aged 40-69 years were approached to participate in the trial.
INTERVENTION: 1,447 men were randomly allocated to either a standard decision aid with a fixed set of five attributes or a personalised decision aid with choice over the inclusion of up to 10 attributes.
OUTCOME MEASURES: To determine whether there was a difference between the two groups in terms of: 1) the emergent opinion (generated by the decision aid) to have a PSA test or not; 2) self-rated decision quality after completing the online decision aid; 3) their intention to undergo screening in the next 12 months. We also wanted to determine whether men in the personalised choice group made use of the extra decision attributes.
RESULTS: 5% of men in the fixed attribute group scored 'Have a PSA test' as the opinion generated by the aid, as compared to 62% of men in the personalised choice group (χ2 = 569.38, 2df, p< 0001). Those men who used the personalised decision aid had slightly higher decision quality (t = 2.157, df = 1444, p = 0.031). The men in the personalised choice group made extensive use of the additional decision attributes. There was no difference between the two groups in terms of their stated intention to undergo screening in the next 12 months.
CONCLUSIONS: Together, these findings suggest that personalised decision support systems could be an important development in shared decision-making and patient-centered care.
TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12612000723886.

Ordóñez-Mena JM, Schöttker B, Mons U, et al.
Quantification of the smoking-associated cancer risk with rate advancement periods: meta-analysis of individual participant data from cohorts of the CHANCES consortium.
BMC Med. 2016; 14:62 [PubMed] Article available free on PMC after 13/04/2017 Related Publications
BACKGROUND: Smoking is the most important individual risk factor for many cancer sites but its association with breast and prostate cancer is not entirely clear. Rate advancement periods (RAPs) may enhance communication of smoking related risk to the general population. Thus, we estimated RAPs for the association of smoking exposure (smoking status, time since smoking cessation, smoking intensity, and duration) with total and site-specific (lung, breast, colorectal, prostate, gastric, head and neck, and pancreatic) cancer incidence and mortality.
METHODS: This is a meta-analysis of 19 population-based prospective cohort studies with individual participant data for 897,021 European and American adults. For each cohort we calculated hazard ratios (HRs) for the association of smoking exposure with cancer outcomes using Cox regression adjusted for a common set of the most important potential confounding variables. RAPs (in years) were calculated as the ratio of the logarithms of the HRs for a given smoking exposure variable and age. Meta-analyses were employed to summarize cohort-specific HRs and RAPs.
RESULTS: Overall, 140,205 subjects had a first incident cancer, and 53,164 died from cancer, during an average follow-up of 12 years. Current smoking advanced the overall risk of developing and dying from cancer by eight and ten years, respectively, compared with never smokers. The greatest advancements in cancer risk and mortality were seen for lung cancer and the least for breast cancer. Smoking cessation was statistically significantly associated with delays in the risk of cancer development and mortality compared with continued smoking.
CONCLUSIONS: This investigation shows that smoking, even among older adults, considerably advances, and cessation delays, the risk of developing and dying from cancer. These findings may be helpful in more effectively communicating the harmful effects of smoking and the beneficial effect of smoking cessation.

Sooriakumaran P, Dev HS, Skarecky D, Ahlering T
The importance of surgical margins in prostate cancer.
J Surg Oncol. 2016; 113(3):310-5 [PubMed] Related Publications
Positive surgical margins (PSM) after radical prostatectomy (RP) are a predictor of biochemical recurrence (BCR), and highly dependent on surgeon, experience, and skill. The length and location PSMs are important, with significant differences between open and robotic RP. The impact of PSMs on BCR remains secondary to other clinico-pathologic variables: Gleason Score, pathologic stage, and baseline PSA. However, lower PSM rates are associated with reduced use of secondary interventions and patient anxiety of cancer recurrence.

Bull CJ, Bonilla C, Holly JM, et al.
Blood lipids and prostate cancer: a Mendelian randomization analysis.
Cancer Med. 2016; 5(6):1125-36 [PubMed] Article available free on PMC after 13/04/2017 Related Publications
Genetic risk scores were used as unconfounded instruments for specific lipid traits (Mendelian randomization) to assess whether circulating lipids causally influence prostate cancer risk. Data from 22,249 prostate cancer cases and 22,133 controls from 22 studies within the international PRACTICAL consortium were analyzed. Allele scores based on single nucleotide polymorphisms (SNPs) previously reported to be uniquely associated with each of low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels, were first validated in an independent dataset, and then entered into logistic regression models to estimate the presence (and direction) of any causal effect of each lipid trait on prostate cancer risk. There was weak evidence for an association between the LDL genetic score and cancer grade: the odds ratio (OR) per genetically instrumented standard deviation (SD) in LDL, comparing high- (≥7 Gleason score) versus low-grade (<7 Gleason score) cancers was 1.50 (95% CI: 0.92, 2.46; P = 0.11). A genetically instrumented SD increase in TGs was weakly associated with stage: the OR for advanced versus localized cancer per unit increase in genetic risk score was 1.68 (95% CI: 0.95, 3.00; P = 0.08). The rs12916-T variant in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) was inversely associated with prostate cancer (OR: 0.97; 95% CI: 0.94, 1.00; P = 0.03). In conclusion, circulating lipids, instrumented by our genetic risk scores, did not appear to alter prostate cancer risk. We found weak evidence that higher LDL and TG levels increase aggressive prostate cancer risk, and that a variant in HMGCR (that mimics the LDL lowering effect of statin drugs) reduces risk. However, inferences are limited by sample size and evidence of pleiotropy.

Heckman MG, Robinson JL, Tzou KS, et al.
An Examination of the Association between FOXA1 Staining Level and Biochemical Recurrence following Salvage Radiation Therapy for Recurrent Prostate Cancer.
PLoS One. 2016; 11(3):e0151785 [PubMed] Article available free on PMC after 13/04/2017 Related Publications
BACKGROUND: Standardly collected clinical and pathological patient information has demonstrated only moderate ability to predict risk of biochemical recurrence (BCR) of prostate cancer in men undergoing salvage radiation therapy (SRT) for a rising PSA after radical prostatectomy (RP). Although elevated FOXA1 staining has been associated with poor patient outcomes following RP, it has not been studied in the specific setting of SRT after RP. The aim of this study was to evaluate the association between FOXA1 staining level and BCR after SRT for recurrent prostate cancer.
METHODS: A total of 141 men who underwent SRT at our institution were included. FOXA1 staining levels in primary tumor samples were detected using immunohistochemistry. FOXA1 staining percentage and intensity were measured and multiplied together to obtain a FOXA1 H-score (range 0-12) which was our primary staining measure. P-values ≤ 0.0056 were considered as statistically significant after applying a Bonferroni correction for multiple comparisons.
RESULTS: There was not a significant association between FOXA1 H-score and risk of BCR when considering H-score as an ordinal variable or as a categorical variable (all P ≥ 0.090). Similarly, no significant associations with BCR were observed for FOXA1 staining percentage or staining intensity (all P ≥ 0.14).
CONCLUSIONS: FOXA1 staining level does not appear to have a major impact on risk of BCR after SRT.

Kandil S, Westwell AD, McGuigan C
7-Substituted umbelliferone derivatives as androgen receptor antagonists for the potential treatment of prostate and breast cancer.
Bioorg Med Chem Lett. 2016; 26(8):2000-4 [PubMed] Related Publications
The clinically used androgen receptor (AR) antagonists (bicalutamide, flutamide and nilutamide) bind with low affinity to AR and can induce escape mechanisms. Furthermore, under AR gene amplification or mutation conditions they demonstrate agonist activity and fail to inhibit AR, causing relapse into castration resistant prostate cancer (CRPC). Discovery of new scaffolds distinct from the 4-cyano/nitro-3-(trifluoromethyl)phenyl group common to currently used antiandrogens is urgently needed to avoid cross-resistance with these compounds. In this study, a series of twenty-nine 7-substituted umbelliferone derivatives was prepared and their antiproliferative activities were evaluated. The most active compound 7a demonstrated submicromolar inhibitory activity in the human prostate cancer cell line (22Rv1); IC50=0.93 μM which represents a 50 fold improvement over the clinical antiandrogen bicalutamide (IC50=46 μM) and a more than 30 fold improvement over enzalutamide (IC50=32 μM). Interestingly, this compound showed even better activity against the human breast cancer cell line (MCF-7); IC50=0.47 μM. Molecular modelling studies provided a plausible theoretical explanation for our findings.

White R, Woolf D, Li S, et al.
Hypofractionated radiotherapy for localized prostate cancer using three-dimensional conformal radiotherapy technique: 3 years toxicity analysis.
Indian J Cancer. 2015 Oct-Dec; 52(4):654-7 [PubMed] Related Publications
BACKGROUND: Hypofractionated radiotherapy in the radical treatment of localized prostate cancer has potential biological advantages relative to conventional fractionation. We report prospectively collected toxicity data from a cohort of patients treated with a 3D conformal technique (3DCRT).
MATERIALS AND METHODS: 90 patients receiving curative intent hypofractionated radiotherapy with 57Gy in 19 daily fractions over 3.8 weeks were evaluated prospectively for the development of radiation related toxicity over a 3 year period.
RESULTS: All patients completed treatment. Maximal acute toxicity experienced was 58.6, 10 and 1.1% for grade 1, 2 and 3 genitourinary (GU) toxicity respectively and 75.6, 9 and 0% for gastrointestinal (GI) toxicity. For late toxicity the three year actuarial rates of grade 1, 2 and 3 GU and GI toxicity respectively were 47.3, 2.4 and 0%; and 40, 9.3 and 4.7%. There were no grade 4 or worse acute or late toxicities. 97.6% of evaluable patients remained free of biochemical failure 36 months post radiotherapy.
CONCLUSIONS: A 57Gy in 19 daily fraction radiotherapy schedule using 3D conformal radiotherapy for the definitive treatment of localized prostate cancer has acceptable early and late toxicity.

Sjöblom L, Saramäki O, Annala M, et al.
Microseminoprotein-Beta Expression in Different Stages of Prostate Cancer.
PLoS One. 2016; 11(3):e0150241 [PubMed] Article available free on PMC after 13/04/2017 Related Publications
Microseminoprotein-beta (MSMB, MSMB) is an abundant secretory protein contributed by the prostate, and is implicated as a prostate cancer (PC) biomarker based on observations of its lower expression in cancerous cells compared with benign prostate epithelium. However, as the current literature on MSMB is inconsistent, we assessed the expression of MSMB at the protein and mRNA levels in a comprehensive set of different clinical stages of PC. Immunohistochemistry using monoclonal and polyclonal antibodies against MSMB was used to study protein expression in tissue specimens representing prostatectomies (n = 261) and in diagnostic needle biopsies from patients treated with androgen deprivation therapy (ADT) (n = 100), and in locally recurrent castration-resistant PC (CRPC) (n = 105) and CRPC metastases (n = 113). The transcript levels of MSMB, nuclear receptor co-activator 4 (NCOA4) and MSMB-NCOA4 fusion were examined by qRT-PCR in prostatectomy samples and by RNA-sequencing in benign prostatic hyperplasia, PC, and CRPC samples. We also measured serum MSMB levels and genotyped the single nucleotide polymorphism rs10993994 using DNA from the blood of 369 PC patients and 903 controls. MSMB expression in PC (29% of prostatectomies and 21% of needle biopsies) was more frequent than in CRPC (9% of locally recurrent CRPCs and 9% of CRPC metastases) (p<0.0001). Detection of MSMB protein was inversely correlated with the Gleason score in prostatectomy specimens (p = 0.024). The read-through MSMB-NCOA4 transcript was detected at very low levels in PC. MSMB levels in serum were similar in cases of PC and controls but were significantly associated with PC risk when adjusted for age at diagnosis and levels of free or total PSA (p<0.001). Serum levels of MSMB in both PC patients and controls were significantly associated with the rs10993994 genotype (p<0.0001). In conclusion, decreased expression of MSMB parallels the clinical progression of PC and adjusted serum MSMB levels are associated with PC risk.

Arthur R, Møller H, Garmo H, et al.
Association between baseline serum glucose, triglycerides and total cholesterol, and prostate cancer risk categories.
Cancer Med. 2016; 5(6):1307-18 [PubMed] Article available free on PMC after 13/04/2017 Related Publications
Lifestyle-related risk factors such as hyperglycemia and dyslipidemia have been associated with several cancers. However, studies exploring their link with prostate cancer (PCa) clinicopathological characteristics are sparse and inconclusive. Here, we investigated the associations between serum metabolic markers and PCa clinicopathological characteristics. The study comprised 14,294 men from the Swedish Apolipoprotein MOrtality RISk (AMORIS) cohort who were diagnosed with PCa between 1996 and 2011. Univariate and multivariable logistic regression were used to investigate the relation between glucose, triglycerides and total cholesterol and PCa risk categories, PSA, Gleason score, and T-stage. Mean age at time of PCa diagnosis was 69 years. Men with glucose levels >6.9 mmol/L tend to have PSA<4 μg/L, while those with glucose levels of 5.6-6.9 mmol/L had a greater odds of PSA>20 μg/L compared to PSA 4.0-9.9 μg/L. Hypertriglyceridemia was also positively associated with PSA>20 μg/L. Hyperglycemic men had a greater odds of intermediate- and high-grade PCa and advanced stage or metastatic PCa. Similarly, hypertriglyceridemia was positively associated with high-grade PCa. There was also a trend toward an increased odds of intermediate risk localized PCa and advanced stage PCa among men with hypertriglyceridemia. Total cholesterol did not have any statistically significant association with any of the outcomes studied. Our findings suggest that high serum levels of glucose and triglycerides may influence PCa aggressiveness and severity. Further investigation on the role of markers of glucose and lipid metabolism in influencing PCa aggressiveness and severity is needed as this may help define important targets for intervention.

Packer JR, Maitland NJ
The molecular and cellular origin of human prostate cancer.
Biochim Biophys Acta. 2016; 1863(6 Pt A):1238-60 [PubMed] Related Publications
Prostate cancer is the most commonly diagnosed male malignancy. Despite compelling epidemiology, there are no definitive aetiological clues linking development to frequency. Pre-malignancies such as proliferative inflammatory atrophy (PIA) and prostatic intraepithelial neoplasia (PIN) yield insights into the initiating events of prostate cancer, as they supply a background "field" for further transformation. An inflammatory aetiology, linked to recurrent prostatitis, and heterologous signalling from reactive stroma and infiltrating immune cells may result in cytokine addiction of cancer cells, including a tumour-initiating population also known as cancer stem cells (CSCs). In prostate tumours, the background mutational rate is rarely exceeded, but genetic change via profound sporadic chromosomal rearrangements results in copy number variations and aberrant gene expression. In cancer, dysfunctional differentiation is imposed upon the normal epithelial lineage, with disruption/disappearance of the basement membrane, loss of the contiguous basal cell layer and expansion of the luminal population. An initiating role for androgen receptor (AR) is attractive, due to the luminal phenotype of the tumours, but alternatively a pool of CSCs, which express little or no AR, has also been demonstrated. Indolent and aggressive tumours may also arise from different stem or progenitor cells. Castrate resistant prostate cancer (CRPC) remains the inevitable final stage of disease following treatment. Time-limited effectiveness of second-generation anti-androgens, and the appearance of an AR-neuroendocrine phenotype imply that metastatic disease is reliant upon the plasticity of the CSC population, and indeed CSC gene expression profiles are most closely related to those identified in CRPCs.

Miftakhova R, Hedblom A, Semenas J, et al.
Cyclin A1 and P450 Aromatase Promote Metastatic Homing and Growth of Stem-like Prostate Cancer Cells in the Bone Marrow.
Cancer Res. 2016; 76(8):2453-64 [PubMed] Related Publications
Bone metastasis is a leading cause of morbidity and mortality in prostate cancer. While cancer stem-like cells have been implicated as a cell of origin for prostate cancer metastasis, the pathways that enable metastatic development at distal sites remain largely unknown. In this study, we illuminate pathways relevant to bone metastasis in this disease. We observed that cyclin A1 (CCNA1) protein expression was relatively higher in prostate cancer metastatic lesions in lymph node, lung, and bone/bone marrow. In both primary and metastatic tissues, cyclin A1 expression was also correlated with aromatase (CYP19A1), a key enzyme that directly regulates the local balance of androgens to estrogens. Cyclin A1 overexpression in the stem-like ALDH(high) subpopulation of PC3M cells, one model of prostate cancer, enabled bone marrow integration and metastatic growth. Further, cells obtained from bone marrow metastatic lesions displayed self-renewal capability in colony-forming assays. In the bone marrow, cyclin A1 and aromatase enhanced local bone marrow-releasing factors, including androgen receptor, estrogen and matrix metalloproteinase MMP9 and promoted the metastatic growth of prostate cancer cells. Moreover, ALDH(high) tumor cells expressing elevated levels of aromatase stimulated tumor/host estrogen production and acquired a growth advantage in the presence of host bone marrow cells. Overall, these findings suggest that local production of steroids and MMPs in the bone marrow may provide a suitable microenvironment for ALDH(high) prostate cancer cells to establish metastatic growths, offering new approaches to therapeutically target bone metastases. Cancer Res; 76(8); 2453-64. ©2016 AACR.

Travis RC, Appleby PN, Martin RM, et al.
A Meta-analysis of Individual Participant Data Reveals an Association between Circulating Levels of IGF-I and Prostate Cancer Risk.
Cancer Res. 2016; 76(8):2288-300 [PubMed] Article available free on PMC after 13/04/2017 Related Publications
The role of insulin-like growth factors (IGF) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3) and prostate cancer risk, we pooled individual participant data from 17 prospective and two cross-sectional studies, including up to 10,554 prostate cancer cases and 13,618 control participants. Conditional logistic regression was used to estimate the ORs for prostate cancer based on the study-specific fifth of each analyte. Overall, IGF-I, IGF-II, IGFBP-2, and IGFBP-3 concentrations were positively associated with prostate cancer risk (Ptrend all ≤ 0.005), and IGFBP-1 was inversely associated weakly with risk (Ptrend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (Pheterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, Pheterogeneity = 0.02). For prospective studies, the OR for men in the highest versus the lowest fifth of each analyte was 1.29 (95% confidence interval, 1.16-1.43) for IGF-I, 0.81 (0.68-0.96) for IGFBP-1, and 1.25 (1.12-1.40) for IGFBP-3. These associations did not differ significantly by time-to-diagnosis or tumor stage or grade. After mutual adjustment for each of the other analytes, only IGF-I remained associated with risk. Our collaborative study represents the largest pooled analysis of the relationship between prostate cancer risk and circulating concentrations of IGF-I, providing strong evidence that IGF-I is highly likely to be involved in prostate cancer development. Cancer Res; 76(8); 2288-300. ©2016 AACR.

Lynch SM, McKenna MM, Walsh CP, McKenna DJ
miR-24 regulates CDKN1B/p27 expression in prostate cancer.
Prostate. 2016; 76(7):637-48 [PubMed] Related Publications
BACKGROUND: MicroRNAs (miRNAs) are small, non-coding RNA molecules with an important role in cancer. In prostate cancer, several miRNAs are expressed abnormally suggesting they may be useful markers for diagnosis, prognosis, and potential therapeutic intervention in this disease. However, the contribution of individual miRNAs to the development and progression of this disease remains poorly understood. This study investigated the role of miR-24, which has not been extensively studied in relation to prostate cancer.
METHODS: We used PCR to investigate the expression of miR-24 in a panel of prostate cancer cell-lines and in a series of clinical prostate biopsy specimens. The biological significance of miR-24 expression in prostate cancer cells was assessed by a series of in vitro bioassays and the effect on proposed targets p27 (CDKN1B) and p16 (CDK2NA) was investigated.
RESULTS: We showed that miR-24 expression was significantly lower in prostate cancer cell lines compared to a normal prostate epithelial cell line. Decreased expression of miR-24 was also more frequently observed in both needle core and prostatectomy tumor tissue relative to matched normal tissue. Low miR-24 expression correlated with high PSA serum levels and other markers of increased prostate cancer progression. Importantly, over-expression of miR-24 inhibited cell cycle, proliferation, migration, and clonogenic potential of prostate cancer cells, as well as inducing apoptosis. p27 and p16 were confirmed as targets of miR-24 in prostate cancer cells and a significant inverse correlation between miR-24 and p27 was revealed in clinical prostatectomy specimens.
CONCLUSIONS: These findings provide evidence that miR-24 has a tumor suppressor role in prostate cancer and also targets p27 and p16 in prostate cancer cells. We propose that it may be a useful progression biomarker or focus of therapeutic intervention for this disease.

Walsh S, Roelofs E, Kuess P, et al.
A validated tumor control probability model based on a meta-analysis of low, intermediate, and high-risk prostate cancer patients treated by photon, proton, or carbon-ion radiotherapy.
Med Phys. 2016; 43(2):734-47 [PubMed] Related Publications
PURPOSE: A fully heterogeneous population averaged mechanistic tumor control probability (TCP) model is appropriate for the analysis of external beam radiotherapy (EBRT). This has been accomplished for EBRT photon treatment of intermediate-risk prostate cancer. Extending the TCP model for low and high-risk patients would be beneficial in terms of overall decision making. Furthermore, different radiation treatment modalities such as protons and carbon-ions are becoming increasingly available. Consequently, there is a need for a complete TCP model.
METHODS: A TCP model was fitted and validated to a primary endpoint of 5-year biological no evidence of disease clinical outcome data obtained from a review of the literature for low, intermediate, and high-risk prostate cancer patients (5218 patients fitted, 1088 patients validated), treated by photons, protons, or carbon-ions. The review followed the preferred reporting item for systematic reviews and meta-analyses statement. Treatment regimens include standard fractionation and hypofractionation treatments. Residual analysis and goodness of fit statistics were applied.
RESULTS: The TCP model achieves a good level of fit overall, linear regression results in a p-value of <0.000 01 with an adjusted-weighted-R(2) value of 0.77 and a weighted root mean squared error (wRMSE) of 1.2%, to the fitted clinical outcome data. Validation of the model utilizing three independent datasets obtained from the literature resulted in an adjusted-weighted-R(2) value of 0.78 and a wRMSE of less than 1.8%, to the validation clinical outcome data. The weighted mean absolute residual across the entire dataset is found to be 5.4%.
CONCLUSIONS: This TCP model fitted and validated to clinical outcome data, appears to be an appropriate model for the inclusion of all clinical prostate cancer risk categories, and allows evaluation of current EBRT modalities with regard to tumor control prediction.

Abend M, Badie C, Quintens R, et al.
Examining Radiation-Induced In Vivo and In Vitro Gene Expression Changes of the Peripheral Blood in Different Laboratories for Biodosimetry Purposes: First RENEB Gene Expression Study.
Radiat Res. 2016; 185(2):109-23 [PubMed] Related Publications
The risk of a large-scale event leading to acute radiation exposure necessitates the development of high-throughput methods for providing rapid individual dose estimates. Our work addresses three goals, which align with the directive of the European Union's Realizing the European Network of Biodosimetry project (EU-RENB): 1. To examine the suitability of different gene expression platforms for biodosimetry purposes; 2. To perform this examination using blood samples collected from prostate cancer patients (in vivo) and from healthy donors (in vitro); and 3. To compare radiation-induced gene expression changes of the in vivo with in vitro blood samples. For the in vitro part of this study, EDTA-treated whole blood was irradiated immediately after venipuncture using single X-ray doses (1 Gy/min(-1) dose rate, 100 keV). Blood samples used to generate calibration curves as well as 10 coded (blinded) samples (0-4 Gy dose range) were incubated for 24 h in vitro, lysed and shipped on wet ice. For the in vivo part of the study PAXgene tubes were used and peripheral blood (2.5 ml) was collected from prostate cancer patients before and 24 h after the first fractionated 2 Gy dose of localized radiotherapy to the pelvis [linear accelerator (LINAC), 580 MU/min, exposure 1-1.5 min]. Assays were run in each laboratory according to locally established protocols using either microarray platforms (2 laboratories) or qRT-PCR (2 laboratories). Report times on dose estimates were documented. The mean absolute difference of estimated doses relative to the true doses (Gy) were calculated. Doses were also merged into binary categories reflecting aspects of clinical/diagnostic relevance. For the in vitro part of the study, the earliest report time on dose estimates was 7 h for qRT-PCR and 35 h for microarrays. Methodological variance of gene expression measurements (CV ≤10% for technical replicates) and interindividual variance (≤twofold for all genes) were low. Dose estimates based on one gene, ferredoxin reductase (FDXR), using qRT-PCR were as precise as dose estimates based on multiple genes using microarrays, but the precision decreased at doses ≥2 Gy. Binary dose categories comprising, for example, unexposed compared with exposed samples, could be completely discriminated with most of our methods. Exposed prostate cancer blood samples (n = 4) could be completely discriminated from unexposed blood samples (n = 4, P < 0.03, two-sided Fisher's exact test) without individual controls. This could be performed by introducing an in vitro-to-in vivo correction factor of FDXR, which varied among the laboratories. After that the in vitro-constructed calibration curves could be used for dose estimation of the in vivo exposed prostate cancer blood samples within an accuracy window of ±0.5 Gy in both contributing qRT-PCR laboratories. In conclusion, early and precise dose estimates can be performed, in particular at doses ≤2 Gy in vitro. Blood samples of prostate cancer patients exposed to 0.09-0.017 Gy could be completely discriminated from pre-exposure blood samples with the doses successfully estimated using adjusted in vitro-constructed calibration curves.

Forootan FS, Forootan SS, Gou X, et al.
Fatty acid activated PPARγ promotes tumorigenicity of prostate cancer cells by up regulating VEGF via PPAR responsive elements of the promoter.
Oncotarget. 2016; 7(8):9322-39 [PubMed] Article available free on PMC after 13/04/2017 Related Publications
In previous work, it is suggested that the excessive amount of fatty acids transported by FABP5 may facilitate the malignant progression of prostate cancer cells through a FABP5-PPARγ-VEGF signal transduction axis to increase angiogenesis. To further functionally characterise the FABP5-PPARγ-VEGF signal transduction pathway, we have, in this work, investigated the molecular mechanisms involved in its tumorigenicity promoting role in prostate cancer. Suppression of PPARγ in highly malignant prostate cancer cells produced a significant reduction (up to 53%) in their proliferation rate, invasiveness (up to 89%) and anchorage-independent growth (up to 94%) in vitro. Knockdown of PPARγ gene in PC3-M cells by siRNA significantly reduced the average size of tumours formed in nude mice by 99% and tumour incidence by 90%, and significantly prolonged the latent period by 3.5 fold. Results in this study combined with some previous results suggested that FABP5 promoted VEGF expression and angiogenesis through PPARγ which was activated by fatty acids transported by FABP5. Further investigations showed that PPARγ up-regulated VEGF expression through acting with the PPAR-responsive elements in the promoter region of VEGF gene in prostate cancer cells. Although androgen can modulate VEGF expression through Sp1/Sp3 binding site on VEGF promoter in androgen-dependent prostate cancer cells, this route, disappeared as the cells gradually lost their androgen dependency; was replaced by the FABP5-PPARγ-VEGF signalling pathway. These results suggested that the FABP5-PPARγ-VEGF signal transduction axis, rather than androgen modulated route, may be a more important novel therapeutic target for angiogenesis-suppression treatment of castration resistant prostate cancer.

Thiruthaneeswaran N, Hoskin PJ
High dose rate brachytherapy for prostate cancer: Standard of care and future direction.
Cancer Radiother. 2016; 20(1):66-72 [PubMed] Related Publications
High dose rate brachytherapy is a highly conformal method of radiation dose escalation for prostate cancer and one of several treatment options for men with localised disease. The large doses per fraction exploit the low alpha/beta ratio of prostate cancer cells so that biological radiation dose delivered is substantially greater than that achieved with conventional external beam delivery. This review article presents contemporary data on the rationale for high dose rate brachytherapy including treatment technique and future directions.

Jolly P, Damborsky P, Madaboosi N, et al.
DNA aptamer-based sandwich microfluidic assays for dual quantification and multi-glycan profiling of cancer biomarkers.
Biosens Bioelectron. 2016; 79:313-9 [PubMed] Related Publications
Two novel sandwich-based immunoassays for prostate cancer (PCa) diagnosis are reported, in which the primary antibody for capture is replaced by a DNA aptamer. The assays, which can be performed in parallel, were developed in a microfluidic device and tested for the detection of free Prostate Specific Antigen (fPSA). A secondary antibody (Aptamer-Antibody Assay) or a lectin (Aptamer-Lectin Assay) is used to quantify, by chemiluminescence, both the amount of fPSA and its glycosylation levels. The use of aptamers enables a more reliable, selective and controlled sensing of the analyte. The dual approach provides sensitive detection of fPSA along with selective fPSA glycoprofiling, which is of significant importance in the diagnosis and prognosis of PCa, as tumor progression is associated with changes in fPSA glycosylation. With these approaches, we can potentially detect 0.5 ng/mL of fPSA and 3 ng/mL of glycosylated fPSA using Sambucus nigra (SNA) lectin, both within the relevant clinical range. The approach can be applied to a wide range of biomarkers, thus providing a good alternative to standard antibody-based immunoassays with significant impact in medical diagnosis and prognosis.

Wu K, Spiegelman D, Hou T, et al.
Associations between unprocessed red and processed meat, poultry, seafood and egg intake and the risk of prostate cancer: A pooled analysis of 15 prospective cohort studies.
Int J Cancer. 2016; 138(10):2368-82 [PubMed] Article available free on PMC after 13/04/2017 Related Publications
Reports relating meat intake to prostate cancer risk are inconsistent. Associations between these dietary factors and prostate cancer were examined in a consortium of 15 cohort studies. During follow-up, 52,683 incident prostate cancer cases, including 4,924 advanced cases, were identified among 842,149 men. Cox proportional hazard models were used to calculate study-specific relative risks (RR) and then pooled using random effects models. Results do not support a substantial effect of total red, unprocessed red and processed meat for all prostate cancer outcomes, except for a modest positive association for tumors identified as advanced stage at diagnosis (advanced(r)). For seafood, no substantial effect was observed for prostate cancer regardless of stage or grade. Poultry intake was inversely associated with risk of advanced and fatal cancers (pooled multivariable RR [MVRR], 95% confidence interval, comparing ≥ 45 vs. <5 g/day: advanced 0.83, 0.70-0.99; trend test p value 0.29), fatal, 0.69, 0.59-0.82, trend test p value 0.16). Participants who ate ≥ 25 versus <5 g/day of eggs (1 egg ∼ 50 g) had a significant 14% increased risk of advanced and fatal cancers (advanced 1.14, 1.01-1.28, trend test p value 0.01; fatal 1.14, 1.00-1.30, trend test p value 0.01). When associations were analyzed separately by geographical region (North America vs. other continents), positive associations between unprocessed red meat and egg intake, and inverse associations between poultry intake and advanced, advanced(r) and fatal cancers were limited to North American studies. However, differences were only statistically significant for eggs. Observed differences in associations by geographical region warrant further investigation.

Thomsen FB, Folkvaljon Y, Garmo H, et al.
Risk of malignant melanoma in men with prostate cancer: Nationwide, population-based cohort study.
Int J Cancer. 2016; 138(9):2154-60 [PubMed] Related Publications
An increased risk of malignant melanoma has been observed in men with prostate cancer. To assess potential shared risk factors and confounding factors, we analysed risk of melanoma in men with prostate cancer including information on tumor characteristics and demographics including socioeconomic status. In The Prostate Cancer data Base Sweden, risk of melanoma was assessed in a cohort of men with prostate cancer and in a comparison cohort of prostate-cancer free men. Data on prostate cancer risk category, melanoma stage, basal cell carcinoma, location of residency, and socioeconomic status were obtained from nationwide registers. Melanoma was diagnosed in 830/108,145 (0.78%) men with prostate cancer and in 3,699/556,792 (0.66%) prostate cancer-free men. In multivariable Cox regression models, men with prostate cancer had a significantly increased risk of melanoma (HR 1.18, 95% CI 1.09-1.27), and so had married men, men with high education and income, and men residing in southern Sweden. The strongest associations were observed for stage 0 melanoma in men with low-risk prostate cancer (HR 1.45, 1.14-1.86), high education (HR 1.87, 1.60-2.18) and top income (HR 1.61, 1.34-1.93), respectively, whereas there was no association between these factors and late-stage melanoma. Men with prostate cancer also had an increased risk of basal cell carcinoma (HR 1.18, 1.15-1.22). In conclusion, men with low-risk prostate cancer, high education, high income and residency in southern Sweden had an increased risk of early-stage melanoma.

Scarbrough PM, Weber RP, Iversen ES, et al.
A Cross-Cancer Genetic Association Analysis of the DNA Repair and DNA Damage Signaling Pathways for Lung, Ovary, Prostate, Breast, and Colorectal Cancer.
Cancer Epidemiol Biomarkers Prev. 2016; 25(1):193-200 [PubMed] Article available free on PMC after 13/04/2017 Related Publications
BACKGROUND: DNA damage is an established mediator of carcinogenesis, although genome-wide association studies (GWAS) have identified few significant loci. This cross-cancer site, pooled analysis was performed to increase the power to detect common variants of DNA repair genes associated with cancer susceptibility.
METHODS: We conducted a cross-cancer analysis of 60,297 single nucleotide polymorphisms, at 229 DNA repair gene regions, using data from the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) Network. Our analysis included data from 32 GWAS and 48,734 controls and 51,537 cases across five cancer sites (breast, colon, lung, ovary, and prostate). Because of the unavailability of individual data, data were analyzed at the aggregate level. Meta-analysis was performed using the Association analysis for SubSETs (ASSET) software. To test for genetic associations that might escape individual variant testing due to small effect sizes, pathway analysis of eight DNA repair pathways was performed using hierarchical modeling.
RESULTS: We identified three susceptibility DNA repair genes, RAD51B (P < 5.09 × 10(-6)), MSH5 (P < 5.09 × 10(-6)), and BRCA2 (P = 5.70 × 10(-6)). Hierarchical modeling identified several pleiotropic associations with cancer risk in the base excision repair, nucleotide excision repair, mismatch repair, and homologous recombination pathways.
CONCLUSIONS: Only three susceptibility loci were identified, which had all been previously reported. In contrast, hierarchical modeling identified several pleiotropic cancer risk associations in key DNA repair pathways.
IMPACT: Results suggest that many common variants in DNA repair genes are likely associated with cancer susceptibility through small effect sizes that do not meet stringent significance testing criteria.

Valerio M, Anele C, Bott SR, et al.
The Prevalence of Clinically Significant Prostate Cancer According to Commonly Used Histological Thresholds in Men Undergoing Template Prostate Mapping Biopsies.
J Urol. 2016; 195(5):1403-8 [PubMed] Related Publications
PURPOSE: Transrectal prostate biopsies are inaccurate and, thus, the prevalence of clinically significant prostate cancer in men undergoing biopsy is unknown. We determined the ability of different histological thresholds to denote clinically significant cancer in men undergoing a more accurate biopsy, that of transperineal template prostate mapping.
MATERIALS AND METHODS: In this multicenter, cross-sectional cohort of men who underwent template prostate mapping biopsies between May 2006 and January 2012, 4 different thresholds of significance combining tumor grade and burden were used to measure the consequent variation with respect to the prevalence of clinically significant disease.
RESULTS: Of 1,203 men 17% (199) had no previous biopsy, 38% (455) had a prior negative transrectal ultrasound biopsy, 24% (289) were on active surveillance and 21% (260) were seeking risk stratification. Mean patient age was 63.5 years (SD 7.6) and median prostate specific antigen was 7.4 ng/ml (IQR 5.3-10.5). Overall 35% of the patients (424) had no cancer detected. The prevalence of clinically significant cancer varied between 14% and 83% according to the histological threshold used, in particular between 30% and 51% among men who had no previous biopsy, between 14% and 27% among men who had a prior negative biopsy, between 36% and 74% among men on active surveillance, and between 47% and 83% among men seeking risk stratification.
CONCLUSIONS: According to template prostate mapping biopsy between 1 in 2 and 1 in 3 men have prostate cancer that is histologically defined as clinically significant. This suggests that the commonly used thresholds may be set too low.

Jarow JP, Ahmed HU, Choyke PL, et al.
Partial Gland Ablation for Prostate Cancer: Report of a Food and Drug Administration, American Urological Association, and Society of Urologic Oncology Public Workshop.
Urology. 2016; 88:8-13 [PubMed] Related Publications
OBJECTIVE: To summarize the discussion that took place at a public workshop, co-sponsored by the U.S. Food and Drug Administration, the American Urological Association, and Society of Urologic Oncology reviewing the current state of the art for partial gland ablation (PGA) for the management of patients with prostate cancer. The purpose of this workshop was to discuss potential indications, current available evidence, and designs for future trials to provide the evidence needed by patients and providers to decide how and when to use PGA.
METHODS: A workshop evaluating PGA for prostate cancer was held in New Orleans, Louisiana, in May 2015. Invited experts representing all stakeholders and attendees discussed the regulatory development of medical products, technology available, potential indications, and designs of trials to evaluate this modality of therapy.
RESULTS: The panel presented the current information on the technologies available to perform PGA, the potential indications, and results of prior consensus conferences. Use of magnetic resonance imaging for patient selection, guide therapy, and follow-up was discussed. Designs of trials to assess PGA outcomes were discussed.
CONCLUSION: The general consensus was that currently available technologies are capable of selective ablation with reasonable accuracy, but that criteria for patient selection remain debatable, and long-term cancer control remains to be established in properly designed and well-performed prospective clinical trials. Concerns include the potential for excessive, unnecessary use in patients with low-risk cancer and, conversely, that current diagnostic techniques may underestimate the extent and aggressiveness of some cancers, leading to inadequate treatment.

James ND, Spears MR, Clarke NW, et al.
Failure-Free Survival and Radiotherapy in Patients With Newly Diagnosed Nonmetastatic Prostate Cancer: Data From Patients in the Control Arm of the STAMPEDE Trial.
JAMA Oncol. 2016; 2(3):348-57 [PubMed] Article available free on PMC after 13/04/2017 Related Publications
IMPORTANCE: The natural history of patients with newly diagnosed high-risk nonmetastatic (M0) prostate cancer receiving hormone therapy (HT) either alone or with standard-of-care radiotherapy (RT) is not well documented. Furthermore, no clinical trial has assessed the role of RT in patients with node-positive (N+) M0 disease. The STAMPEDE Trial includes such individuals, allowing an exploratory multivariate analysis of the impact of radical RT.
OBJECTIVE: To describe survival and the impact on failure-free survival of RT by nodal involvement in these patients.
DESIGN, SETTING, AND PARTICIPANTS: Cohort study using data collected for patients allocated to the control arm (standard-of-care only) of the STAMPEDE Trial between October 5, 2005, and May 1, 2014. Outcomes are presented as hazard ratios (HRs) with 95% CIs derived from adjusted Cox models; survival estimates are reported at 2 and 5 years. Participants were high-risk, hormone-naive patients with newly diagnosed M0 prostate cancer starting long-term HT for the first time. Radiotherapy is encouraged in this group, but mandated for patients with node-negative (N0) M0 disease only since November 2011.
EXPOSURES: Long-term HT either alone or with RT, as per local standard. Planned RT use was recorded at entry.
MAIN OUTCOMES AND MEASURES: Failure-free survival (FFS) and overall survival.
RESULTS: A total of 721 men with newly diagnosed M0 disease were included: median age at entry, 66 (interquartile range [IQR], 61-72) years, median (IQR) prostate-specific antigen level of 43 (18-88) ng/mL. There were 40 deaths (31 owing to prostate cancer) with 17 months' median follow-up. Two-year survival was 96% (95% CI, 93%-97%) and 2-year FFS, 77% (95% CI, 73%-81%). Median (IQR) FFS was 63 (26 to not reached) months. Time to FFS was worse in patients with N+ disease (HR, 2.02 [95% CI, 1.46-2.81]) than in those with N0 disease. Failure-free survival outcomes favored planned use of RT for patients with both N0M0 (HR, 0.33 [95% CI, 0.18-0.61]) and N+M0 disease (HR, 0.48 [95% CI, 0.29-0.79]).
CONCLUSIONS AND RELEVANCE: Survival for men entering the cohort with high-risk M0 disease was higher than anticipated at study inception. These nonrandomized data were consistent with previous trials that support routine use of RT with HT in patients with N0M0 disease. Additionally, the data suggest that the benefits of RT extend to men with N+M0 disease.
TRIAL REGISTRATION: Identifier: NCT00268476; ISRCTN78818544.

Khalid T, Aggio R, White P, et al.
Urinary Volatile Organic Compounds for the Detection of Prostate Cancer.
PLoS One. 2015; 10(11):e0143283 [PubMed] Article available free on PMC after 13/04/2017 Related Publications
The aim of this work was to investigate volatile organic compounds (VOCs) emanating from urine samples to determine whether they can be used to classify samples into those from prostate cancer and non-cancer groups. Participants were men referred for a trans-rectal ultrasound-guided prostate biopsy because of an elevated prostate specific antigen (PSA) level or abnormal findings on digital rectal examination. Urine samples were collected from patients with prostate cancer (n = 59) and cancer-free controls (n = 43), on the day of their biopsy, prior to their procedure. VOCs from the headspace of basified urine samples were extracted using solid-phase micro-extraction and analysed by gas chromatography/mass spectrometry. Classifiers were developed using Random Forest (RF) and Linear Discriminant Analysis (LDA) classification techniques. PSA alone had an accuracy of 62-64% in these samples. A model based on 4 VOCs, 2,6-dimethyl-7-octen-2-ol, pentanal, 3-octanone, and 2-octanone, was marginally more accurate 63-65%. When combined, PSA level and these four VOCs had mean accuracies of 74% and 65%, using RF and LDA, respectively. With repeated double cross-validation, the mean accuracies fell to 71% and 65%, using RF and LDA, respectively. Results from VOC profiling of urine headspace are encouraging and suggest that there are other metabolomic avenues worth exploring which could help improve the stratification of men at risk of prostate cancer. This study also adds to our knowledge on the profile of compounds found in basified urine, from controls and cancer patients, which is useful information for future studies comparing the urine from patients with other disease states.

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