Prostate Cancer
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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

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Prostate Cancer Screening

Information Patients and the Public (10 links)


Information for Health Professionals / Researchers (4 links)

Latest Research Publications

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

Patel R, Gao M, Ahmad I, et al.
Sprouty2, PTEN, and PP2A interact to regulate prostate cancer progression.
J Clin Invest. 2013; 123(3):1157-75 [PubMed] Free Access to Full Article
Concurrent activation of RAS/ERK and PI3K/AKT pathways is implicated in prostate cancer progression. The negative regulators of these pathways, including sprouty2 (SPRY2), protein phosphatase 2A (PP2A), and phosphatase and tensin homolog (PTEN), are commonly inactivated in prostate cancer. The molecular basis of cooperation between these genetic alterations is unknown. Here, we show that SPRY2 deficiency alone triggers activation of AKT and ERK, but this is insufficient to drive tumorigenesis. In addition to AKT and ERK activation, SPRY2 loss also activates a PP2A-dependent tumor suppressor checkpoint. Mechanistically, the PP2A-mediated growth arrest depends on GSK3β and is ultimately mediated by nuclear PTEN. In murine prostate cancer models, Pten haploinsufficiency synergized with Spry2 deficiency to drive tumorigenesis, including metastasis. Together, these results show that loss of Pten cooperates with Spry2 deficiency by bypassing a novel tumor suppressor checkpoint. Furthermore, loss of SPRY2 expression correlates strongly with loss of PTEN and/or PP2A subunits in human prostate cancer. This underlines the cooperation between SPRY2 deficiency and PTEN or PP2A inactivation in promoting tumorigenesis. Overall, we propose SPRY2, PTEN, and PP2A status as an important determinant of prostate cancer progression. Characterization of this trio may facilitate patient stratification for targeted therapies and chemopreventive interventions.
The Beatson Institute for Cancer Research, Glasgow
Research funded by:


Muthana M, Rodrigues S, Chen YY, et al.
Macrophage delivery of an oncolytic virus abolishes tumor regrowth and metastasis after chemotherapy or irradiation.
Cancer Res. 2013; 73(2):490-5 [PubMed]
Frontline anticancer therapies such as chemotherapy and irradiation often slow tumor growth, but tumor regrowth and spread to distant sites usually occurs after the conclusion of treatment. We recently showed that macrophages could be used to deliver large quantities of a hypoxia-regulated, prostate-specific oncolytic virus (OV) to prostate tumors. In the current study, we show that administration of such OV-armed macrophages 48 hours after chemotherapy (docetaxel) or tumor irradiation abolished the posttreatment regrowth of primary prostate tumors in mice and their spread to the lungs for up to 27 or 40 days, respectively. It also significantly increased the lifespan of tumor-bearing mice compared with those given docetaxel or irradiation alone. These new findings suggest that such a novel, macrophage-based virotherapy could be used to markedly increase the efficacy of chemotherapy and irradiation in patients with prostate cancer.
Academic Unit of Inflammation & Tumor Targeting, University of Sheffield Medical School, Sheffield


Méplan C, Rohrmann S, Steinbrecher A, et al.
Polymorphisms in thioredoxin reductase and selenoprotein K genes and selenium status modulate risk of prostate cancer.
PLoS One. 2012; 7(11):e48709 [PubMed] Free Access to Full Article
Increased dietary intake of Selenium (Se) has been suggested to lower prostate cancer mortality, but supplementation trials have produced conflicting results. Se is incorporated into 25 selenoproteins. The aim of this work was to assess whether risk of prostate cancer is affected by genetic variants in genes coding for selenoproteins, either alone or in combination with Se status. 248 cases and 492 controls from an EPIC-Heidelberg nested case-control study were subjected to two-stage genotyping with an initial screening phase in which 384 tagging-SNPs covering 72 Se-related genes were determined in 94 cases and 94 controls using the Illumina Goldengate methodology. This analysis was followed by a second phase in which genotyping for candidate SNPs identified in the first phase was carried out in the full study using Sequenom. Risk of high-grade or advanced stage prostate cancer was modified by interactions between serum markers of Se status and genotypes for rs9880056 in SELK, rs9605030 and rs9605031 in TXNRD2, and rs7310505 in TXNRD1. No significant effects of SNPs on prostate cancer risk were observed when grade or Se status was not taken into account. In conclusion, the risk of high-grade or advanced-stage prostate cancer is significantly altered by a combination of genotype for SNPs in selenoprotein genes and Se status. The findings contribute to explaining the biological effects of selenium intake and genetic factors in prostate cancer development and highlight potential roles of thioredoxin reductases and selenoprotein K in tumour progression.
Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle-upon-Tyne


Dixit S, Coup A, Hunt C, Coombs L
Small cell cancer of the prostate.
Urology. 2012; 80(5):e58-60 [PubMed]
De novo small cell cancer of the prostate is a rare tumor and has different presentation, behavior, and outcome compared with adenocarcinoma. A 66-year-old man presented with symptoms masquerading as a rectal tumor. Primary symptoms were intermittent constipation and diarrhea without any urinary symptoms. Initial staging showed only 2 large pelvic nodes. Prostate-specific antigen was 4.8 ng/L. A transrectal prostate biopsy confirmed small cell histology. After having no response to hormones and carboplatin-etoposide, a course of palliative radiotherapy, docetaxel chemotherapy, and defunctioning colostomy offered palliation. Liver and lytic bone metastases developed later; the patient died 9 months after the presentation.
Castle Hill Hospital, Hull and East Yorkshire NHS Trust, Hull


Yamamoto H, Masters JR, Dasgupta P, et al.
CD49f is an efficient marker of monolayer- and spheroid colony-forming cells of the benign and malignant human prostate.
PLoS One. 2012; 7(10):e46979 [PubMed] Free Access to Full Article
Stem cells may play a role in the development and maintenance of proliferative diseases of the prostate such as prostate cancer and benign prostatic hyperplasia. Cell membrane protein markers, CD49f, CD133 and CD44, have been shown to identify putative prostate stem cells, but a lack of consensus exists with regards to the most efficient marker(s) for stem-like cell identification. This study aimed to determine whether previously reported markers had equal capacity to select monolayer and spheroid colony-forming cells (CFCs), which were used as surrogate readouts of stem-like cells, and to characterize the expression of CD49f, CD44 and CD133 by flow cytometry and immunohistochemistry.In benign prostate cells, CD49f+, CD44+, and CD133+ cells represented 5.6±3.1%, 28.2±4.1% and 0.10±0.06% of total cells. Both monolayer- and spheroid-CFCs existed at a frequency of approximately 0.5% of total cells. CD49f+, CD44+, and CD133+ subpopulations differed significantly in their ability to select benign CFCs. The highest recovery of CFCs was achieved by CD49f+ selection (98%), whereas CD44+ or CD133+ selection led to poor CFC-recovery (17% and 3%, respectively). For the first time, we show highly efficient recovery of CFCs from advanced prostate cancer by CD49f+, but not by CD44+ or CD133+ selection. Furthermore, CD133 expression (AC133 clone) could not be detected in benign prostate cells by either immunohistochemistry or flow cytometry. We conclude that CD49f, but not previously described stem cell markers CD133 and CD44, to be optimal for selection of monolayer- and spheroid-CFCs in the benign and malignant prostate.
Prostate Cancer Research Center, Division of Surgery and Interventional Science, University College London, London
Research funded by:


McKee CM, Xu D, Cao Y, et al.
Protease nexin 1 inhibits hedgehog signaling in prostate adenocarcinoma.
J Clin Invest. 2012; 122(11):4025-36 [PubMed] Free Access to Full Article
Prostate adenocarcinoma (CaP) patients are classified into low-, intermediate-, and high-risk groups that reflect relative survival categories. While there are accepted treatment regimens for low- and high-risk patients, intermediate-risk patients pose a clinical dilemma, as treatment outcomes are highly variable for these individuals. A better understanding of the factors that regulate the progression of CaP is required to delineate risk. For example, aberrant activation of the Hedgehog (Hh) pathway is implicated in CaP progression. Here, we identify the serine protease inhibitor protease nexin 1 (PN1) as a negative regulator of Hh signaling in prostate. Using human CaP cell lines and a mouse xenograft model of CaP, we demonstrate that PN1 regulates Hh signaling by decreasing protein levels of the Hh ligand Sonic (SHH) and its downstream effectors. Furthermore, we show that SHH expression enhanced tumor growth while overexpression of PN1 inhibited tumor growth and angiogenesis in mice. Finally, using comparative genome hybridization, we found that genetic alterations in Hh pathway genes correlated with worse clinical outcomes in intermediate-risk CaP patients, indicating the importance of this pathway in CaP.
Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford
Research funded by:


Payne HA, Hughes S
Radical radiotherapy for high-risk prostate cancer in older men.
Oncologist. 2012; 17 Suppl 1:9-15 [PubMed] Article available free on PMC after 01/09/2013
Historical data for older men with high-risk nonmetastatic prostate cancer treated with radiotherapy alone have demonstrated a 10-year prostate-cancer-specific mortality of around 30%. The development of dose escalation, using techniques such as intensity-modulated radiotherapy, has enabled more targeted delivery of treatment with improved efficacy and a reduction in the risk of toxicity compared with conventional radiotherapy. The combination of radiotherapy and androgen-deprivation therapy (ADT) has been shown to improve overall survival compared with radiotherapy or ADT alone without a significant increase in toxicity in patients with minimal comorbidities. There is evidence that patient age has only a marginal effect on genitourinary and gastrointestinal toxicities following radiotherapy. Further research has shown that although age does have an effect on the likelihood of sexual dysfunction after radiation therapy, there is no significant difference in the proportion of men aged ≥ 75 years who feel that sexual dysfunction is a moderate or serious problem before or 24 months after diagnosis. Radical radiotherapy is effective and well tolerated in senior men with high-risk prostate cancer and should be offered in combination with long-term ADT to patients with minimal comorbidities. In case of significant comorbid conditions, shorter durations of ADT may be considered.
University College London Hospitals, London NW1 2PG


Zuccolo L, Lewis SJ, Donovan JL, et al.
Alcohol consumption and PSA-detected prostate cancer risk--a case-control nested in the ProtecT study.
Int J Cancer. 2013; 132(9):2176-85 [PubMed]
Alcohol is an established carcinogen but not an established risk factor for prostate cancer, despite some recent prospective studies suggesting increased risk among heavy drinkers. The aim of this study was to investigate the role of alcohol on prostate-specific antigen (PSA) levels and prostate cancer risk. Two thousand four hundred PSA detected prostate cancer cases and 12,700 controls matched on age and general practice were identified through a case-control study nested in the PSA-testing phase of a large UK-based randomized controlled trial for prostate cancer treatment (ProtecT). Linear and multinomial logistic regression models were used to estimate ratios of geometric means (RGMs) of PSA and relative risk ratios (RRRs) of prostate cancer by stage and grade, with 95% confidence intervals (CIs), associated with weekly alcohol intake and drinking patterns. We found evidence of lower PSA (RGM 0.98, 95% CI: 0.98-0.99) and decreased risk of low Gleason-grade (RRR 0.96; 95%CI 0.93-0.99) but increased risk of high-grade prostate cancer (RRR 1.04; 95%CI 0.99-1.08; p(difference) =0.004) per 10 units/week increase in alcohol consumption, not explained by current BMI, blood pressure, comorbidities, or reverse causation. This is the first large population-based study to find evidence of lower PSA levels for increasing alcohol consumption, with potential public health implications for the detection of prostate cancer. Our results also support a modestly higher risk of high-grade disease for heavy drinkers, but require independent replication to establish the nature of the association of alcohol with low-grade disease, preferably in cohorts with a heterogeneous case-mix.
MRC Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol
Research funded by:


Melchini A, Needs PW, Mithen RF, Traka MH
Enhanced in vitro biological activity of synthetic 2-(2-pyridyl) ethyl isothiocyanate compared to natural 4-(methylsulfinyl) butyl isothiocyanate.
J Med Chem. 2012; 55(22):9682-92 [PubMed]
Dietary isothiocyanates (ITC) derived from cruciferous vegetables have been shown to have numerous biological effects consistent with chemoprotective activity. In this study we synthesized a novel ITC, 2-(2-pyridyl) ethyl ITC (PY-ITC), and assessed its chemopreventive ability in comparison to sulforaphane (SF), the ITC derived from broccoli. PY-ITC suppressed cancerous cell growth and proliferation at lower concentrations than SF and was more potent at inducing p21 protein. Through the use of whole genome arrays we demonstrate that prostate cells exposed to PY-ITC or SF have similar biological response, albeit PY-ITC alters a greater number of genes, and to a greater extent. In the presence of a phosphatidylinositol-3-kinase (PI3K) inhibitor PY-ITC had a more pronounced effect on gene expression, emphasizing the important role of PI3K/AKT signaling in mediating the chemopreventive effects of ITCs. These results highlight the importance of the ITC side chain in bioactivity.
Food & Health Programme, Institute of Food Research , Norwich Research Park, NR4 7UA United Kingdom.
Research funded by:


Harris V, Benton B, Sohaib A, et al.
Bile acid malabsorption after pelvic and prostate intensity modulated radiation therapy: an uncommon but treatable condition.
Int J Radiat Oncol Biol Phys. 2012; 84(5):e601-6 [PubMed]
PURPOSE: Intensity modulated radiation therapy (IMRT) is a significant therapeutic advance in prostate cancer, allowing increased tumor dose delivery and increased sparing of normal tissues. IMRT planning uses strict dose constraints to nearby organs to limit toxicity. Bile acid malabsorption (BAM) is a treatable disorder of the terminal ileum (TI) that presents with symptoms similar to radiation therapy toxicity. It has not been described in patients receiving RT for prostate cancer in the contemporary era. We describe new-onset BAM in men after IMRT for prostate cancer.
METHODS AND MATERIALS: Diagnosis of new-onset BAM was established after typical symptoms developed, selenium-75 homocholic acid taurine (SeHCAT) scanning showed 7-day retention of <15%, and patients' symptoms unequivocally responded to a bile acid sequestrant. The TI was identified on the original radiation therapy plan, and the radiation dose delivered was calculated and compared with accepted dose-volume constraints.
RESULTS: Five of 423 men treated in a prospective series of high-dose prostate and pelvic IMRT were identified with new onset BAM (median age, 65 years old). All reported having normal bowel habits before RT. The volume of TI ranged from 26-141 cc. The radiation dose received by the TI varied between 11.4 Gy and 62.1 Gy (uncorrected). Three of 5 patients had TI treated in excess of 45 Gy (equivalent dose calculated in 2-Gy fractions, using an α/β ratio of 3) with volumes ranging from 1.6 cc-49.0 cc. One patient had mild BAM (SeHCAT retention, 10%-15%), 2 had moderate BAM (SeHCAT retention, 5%-10%), and 2 had severe BAM (SeHCAT retention, <5%). The 3 patients whose TI received ≥45 Gy developed moderate to severe BAM, whereas those whose TI received <45 Gy had only mild to moderate BAM.
CONCLUSIONS: Radiation delivered to the TI during IMRT may cause BAM. Identification of the TI from unenhanced RT planning computed tomography scans is difficult and may impede accurate dosimetric evaluation. Thorough toxicity assessment and close liaison between oncologist and gastroenterologist allow timely diagnosis and treatment.
Academic Urology Unit, Institute of Cancer Research and The Royal Marsden Hospital, London and Sutton


Tucci P, Agostini M, Grespi F, et al.
Loss of p63 and its microRNA-205 target results in enhanced cell migration and metastasis in prostate cancer.
Proc Natl Acad Sci U S A. 2012; 109(38):15312-7 [PubMed] Article available free on PMC after 01/09/2013
p63 inhibits metastasis. Here, we show that p63 (both TAp63 and ΔNp63 isoforms) regulates expression of miR-205 in prostate cancer (PCa) cells, and miR-205 is essential for the inhibitory effects of p63 on markers of epithelial-mesenchymal transition (EMT), such as ZEB1 and vimentin. Correspondingly, the inhibitory effect of p63 on EMT markers and cell migration is reverted by anti-miR-205. p53 mutants inhibit expression of both p63 and miR-205, and the cell migration, in a cell line expressing endogenous mutated p53, can be abrogated by pre-miR-205 or silencing of mutated p53. In accordance with this in vitro data, ΔNp63 or miR-205 significantly inhibits the incidence of lung metastasis in vivo in a mouse tail vein model. Similarly, one or both components of the p63/miR-205 axis were absent in metastases or colonized lymph nodes in a set of 218 human prostate cancer samples. This was confirmed in an independent clinical data set of 281 patients. Loss of this axis was associated with higher Gleason scores, an increased likelihood of metastatic and infiltration events, and worse prognosis. These data suggest that p63/miR-205 may be a useful clinical predictor of metastatic behavior in prostate cancer.
Medical Research Council, Toxicology Unit, Leicester University, Leicester
Research funded by:


Ming L, Byrne NM, Camac SN, et al.
Androgen deprivation results in time-dependent hypoxia in LNCaP prostate tumours: informed scheduling of the bioreductive drug AQ4N improves treatment response.
Int J Cancer. 2013; 132(6):1323-32 [PubMed]
Androgen withdrawal induces hypoxia in androgen-sensitive tissue; this is important as in the tumour microenvironment, hypoxia is known to drive malignant progression. Our study examined the time-dependent effect of androgen deprivation therapy (ADT) on tumour oxygenation and investigated the role of ADT-induced hypoxia on malignant progression in prostate tumours. LNCaP xenografted tumours were treated with anti-androgens and tumour oxygenation measured. Dorsal skin fold (DSF) chambers were used to image tumour vasculature in vivo. Quantitative PCR (QPCR) identified differential gene expression following treatment with bicalutamide. Bicalutamide-treated and vehicle-only-treated tumours were re-established in vitro, and invasion and sensitivity to docetaxel were measured. Tumour growth delay was calculated following treatment with bicalutamide combined with the bioreductive drug AQ4N. Tumour oxygenation measurements showed a precipitate decrease following initiation of ADT. A clinically relevant dose of bicalutamide (2 mg/kg/day) decreased tumour oxygenation by 45% within 24 hr, reaching a nadir of 0.09% oxygen (0.67 ± 0.06 mmHg) by Day 7; this persisted until Day 14 when it increased up to Day 28. Using DSF chambers, LNCaP tumours treated with bicalutamide showed loss of small vessels at Days 7 and 14 with revascularisation occurring by Day 21. QPCR showed changes in gene expression consistent with the vascular changes and malignant progression. Cells from bicalutamide-treated tumours were more malignant than vehicle-treated controls. Combining bicalutamide with AQ4N (50 mg/kg, single dose) caused greater tumour growth delay than bicalutamide alone. Our study shows that bicalutamide-induced hypoxia selects for cells that show malignant progression; targeting hypoxic cells may provide greater clinical benefit.
Biomedical Sciences Research Institute, Centre for Molecular Biosciences, University of Ulster, Coleraine, Co-Londonderry


Ahmed HU, Cathcart P, McCartan N, et al.
Focal salvage therapy for localized prostate cancer recurrence after external beam radiotherapy: a pilot study.
Cancer. 2012; 118(17):4148-55 [PubMed]
BACKGROUND: The objective of this study was to evaluate the safety, feasibility, side-effect profile, and proof of concept for focal salvage therapy using high-intensity focused ultrasound (HIFU).
METHODS: A registry-based analysis was conducted between 2004 and 2009 of 430 patients who underwent HIFU. Thirty-nine patients received focal salvage therapy for localized recurrence after external beam radiotherapy. Multiparametric magnetic resonance imaging studies combined with transperineal template prostate mapping biopsies or transrectal biopsies were used to localize disease. Validated questionnaires were used to assess functional outcomes. Biochemical failure was defined by using both Phoenix criteria (prostate-specific antigen [PSA] nadir plus 2 ng/mL) and Stuttgart criteria (PSA nadir plus 1.2 ng/mL).
RESULTS: The mean pre-HIFU PSA level was 4.6 ng/mL. The median follow-up was 17 months (interquartile range, 10-29 months). International Index of Erectile Function-5 scores decreased from a median ± standard deviation (SD) of 18 ± 16 to 13 ± 21 at 6 months, demonstrating worsening function. Scores on the University of California Los Angeles-Expanded Prostate Cancer Index Composite Urinary domain indicate that pad-free, leak-free continence status was 64%, and the pad-free rate was 87.2% at last follow-up. One rectourethral fistula occurred and spontaneously resolved with urinary and bowel diversion. The actuarial progression-free survival rate (including PSA nonresponders) was 69% at 1 year and 49% at 2 years according to Phoenix criteria. Excluding PSA nonresponders, these rates were 74% and 58%, respectively (Phoenix criteria).
CONCLUSIONS: The results from this study indicated that focal salvage therapy is a potential strategy for localized recurrence after radiotherapy that may reduce the harms resulting from whole-gland salvage therapies.
Division of Surgery and Interventional Science, University College London, London
Research funded by:


Reebye V, Querol Cano L, Lavery DN, et al.
Role of the HSP90-associated cochaperone p23 in enhancing activity of the androgen receptor and significance for prostate cancer.
Mol Endocrinol. 2012; 26(10):1694-706 [PubMed]
Prostate tumor growth initially depends on androgens, which act via the androgen receptor (AR). Despite androgen ablation therapy, tumors eventually progress to a castrate-resistant stage in which the AR remains active. The mechanisms are poorly understood but it may be that changes in levels or activity of AR coregulators affect trafficking and activation of the receptor. A key stage in AR signaling occurs in the cytoplasm, where unliganded receptor is associated with the heat shock protein (HSP)90 foldosome complex. p23, a key component of this complex, is best characterized as a cochaperone for HSP90 but also has HSP90-independent activity and has been reported as having differential effects on the activity of different steroid receptors. Here we report that p23 increases activity of the AR, and this appears to involve steps both in the cytoplasm (increasing ligand-binding capacity, possibly via direct interaction with AR) and the nucleus (enhancing AR occupancy at target promoters). We show, for the first time, that AR and p23 can interact, perhaps directly, when HSP90 is not present in the same complex. The effects of p23 on AR activity are at least partly HSP90 independent because a mutant form of p23, unable to bind HSP90, nevertheless increases AR activity. In human prostate tumors, nuclear p23 was higher in malignant prostate cells compared with benign/normal cells, supporting the utility of p23 as a therapeutic target in prostate cancer.
Androgen Signaling Laboratory, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN
Research funded by:


Newcombe PJ, Reck BH, Sun J, et al.
A comparison of Bayesian and frequentist approaches to incorporating external information for the prediction of prostate cancer risk.
Genet Epidemiol. 2012; 36(1):71-83 [PubMed]
We present the most comprehensive comparison to date of the predictive benefit of genetics in addition to currently used clinical variables, using genotype data for 33 single-nucleotide polymorphisms (SNPs) in 1,547 Caucasian men from the placebo arm of the REduction by DUtasteride of prostate Cancer Events (REDUCE®) trial. Moreover, we conducted a detailed comparison of three techniques for incorporating genetics into clinical risk prediction. The first method was a standard logistic regression model, which included separate terms for the clinical covariates and for each of the genetic markers. This approach ignores a substantial amount of external information concerning effect sizes for these Genome Wide Association Study (GWAS)-replicated SNPs. The second and third methods investigated two possible approaches to incorporating meta-analysed external SNP effect estimates - one via a weighted PCa 'risk' score based solely on the meta analysis estimates, and the other incorporating both the current and prior data via informative priors in a Bayesian logistic regression model. All methods demonstrated a slight improvement in predictive performance upon incorporation of genetics. The two methods that incorporated external information showed the greatest receiver-operating-characteristic AUCs increase from 0.61 to 0.64. The value of our methods comparison is likely to lie in observations of performance similarities, rather than difference, between three approaches of very different resource requirements. The two methods that included external information performed best, but only marginally despite substantial differences in complexity.
Genetics Division, GlaxoSmithKline, Stevenage
Research funded by:


Henke A, Grace OC, Ashley GR, et al.
Stromal expression of decorin, Semaphorin6D, SPARC, Sprouty1 and Tsukushi in developing prostate and decreased levels of decorin in prostate cancer.
PLoS One. 2012; 7(8):e42516 [PubMed] Article available free on PMC after 01/09/2013
BACKGROUND AND AIM: During prostate development, mesenchymal-epithelial interactions regulate organ growth and differentiation. In adult prostate, stromal-epithelial interactions are important for tissue homeostasis and also play a significant role in prostate cancer. In this study we have identified molecules that show a mesenchymal expression pattern in the developing prostate, and one of these showed reduced expression in prostate cancer stroma.
METHODOLOGY AND PRINCIPAL FINDINGS: Five candidate molecules identified by transcript profiling of developmental prostate mesenchyme were selected using a wholemount in situ hybridisation screen and studied Decorin (Dcn), Semaphorin6D (Sema6D), SPARC/Osteonectin (SPARC), Sprouty1 (Spry-1) and Tsukushi (Tsku). Expression in rat tissues was evaluated using wholemount in situ hybridisation (postnatal day (P) 0.5) and immunohistochemistry (embryonic day (E) E17.5, E19.5; P0.5; P6; 28 & adult). Four candidates (Decorin, SPARC, Spry-1, Tsukushi) were immunolocalised in human foetal prostate (weeks 14, 16, 19) and expression of Decorin was evaluated on a human prostate cancer tissue microarray. In embryonic and perinatal rats Decorin, Semaphorin6D, SPARC, Spry-1 and Tsukushi were expressed with varying distribution patterns throughout the mesenchyme at E17.5, E19.5, P0.5 and P6.5. In P28 and adult prostates there was either a decrease in the expression (Semaphorin6D) or a switch to epithelial expression of SPARC, and Spry-1, whereas Decorin and Tsukushi were specific to mesenchyme/stroma at all ages. Expression of Decorin, SPARC, Spry-1 and Tsukushi in human foetal prostates paralleled that in rat. Decorin showed mesenchymal and stromal-specific expression at all ages and was further examined in prostate cancer, where stromal expression was significantly reduced compared with non-malignant prostate.
CONCLUSION AND SIGNIFICANCE: We describe the spatio-temporal expression of Decorin, Semaphorin6D, SPARC, Spry-1 and Tsukushi in developing prostate and observed similar mesenchymal expression patterns in rat and human. Additionally, Decorin showed reduced expression in prostate cancer stroma compared to non-malignant prostate stroma.
Medical Research Council, Centre for Reproductive Health, The Queens's Medical Research Institute, Edinburgh, Scotland
Research funded by:


Addeo A, Rinaldi C, Panades M
A case of small cell carcinoma of the prostate and review of the literature.
Tumori. 2012 May-Jun; 98(3):76e-78e [PubMed]
AIM AND BACKGROUND: Small cell carcinoma of the prostate (SCCP) is a relatively rare entity, an aggressive tumor with a tendency to metastasize early. There is no standard chemotherapy regimen for SCCP. We report the case of a 67-year-old man with an initial diagnosis of prostate adenocarcinoma with bone metastases who subsequently developed a small cell carcinoma of the prostate with liver metastases.
METHODS AND STUDY DESIGN: A review of this case and of the current literature was done with a view to highlighting the ideal approach to such an unusual tumor.
RESULTS AND CONCLUSION: The patient was treated with carboplatin and etoposide and after 3 cycles achieved a good response. Unfortunately he developed massive pulmonary embolism which impeded the continuation of treatment and caused his death. By reviewing the literature we found there is no standard of care and new targeted therapies have failed to prove any benefit so far. It is mandatory to persevere in planning trials and exploring new drugs to improve the outcome of patients with SCCP. It might also be worth creating a register for SCCP where data can be collected to coordinate the management of these patients and to establish better connections among cancer centers.
Oncology Department, United Lincolnshire Hospitals NHS Trust, Lincoln and Boston


Glaab E, Bacardit J, Garibaldi JM, Krasnogor N
Using rule-based machine learning for candidate disease gene prioritization and sample classification of cancer gene expression data.
PLoS One. 2012; 7(7):e39932 [PubMed] Article available free on PMC after 01/09/2013
Microarray data analysis has been shown to provide an effective tool for studying cancer and genetic diseases. Although classical machine learning techniques have successfully been applied to find informative genes and to predict class labels for new samples, common restrictions of microarray analysis such as small sample sizes, a large attribute space and high noise levels still limit its scientific and clinical applications. Increasing the interpretability of prediction models while retaining a high accuracy would help to exploit the information content in microarray data more effectively. For this purpose, we evaluate our rule-based evolutionary machine learning systems, BioHEL and GAssist, on three public microarray cancer datasets, obtaining simple rule-based models for sample classification. A comparison with other benchmark microarray sample classifiers based on three diverse feature selection algorithms suggests that these evolutionary learning techniques can compete with state-of-the-art methods like support vector machines. The obtained models reach accuracies above 90% in two-level external cross-validation, with the added value of facilitating interpretation by using only combinations of simple if-then-else rules. As a further benefit, a literature mining analysis reveals that prioritizations of informative genes extracted from BioHEL's classification rule sets can outperform gene rankings obtained from a conventional ensemble feature selection in terms of the pointwise mutual information between relevant disease terms and the standardized names of top-ranked genes.
Interdisciplinary Computing and Complex Systems Research Group, University of Nottingham, Nottingham


Adam V, Ekblad M, Sweeney K, et al.
Synergistic and Selective Cancer Cell Killing Mediated by the Oncolytic Adenoviral Mutant AdΔΔ and Dietary Phytochemicals in Prostate Cancer Models.
Hum Gene Ther. 2012; 23(9):1003-15 [PubMed] Article available free on PMC after 01/09/2013
AdΔΔ is an oncolytic adenoviral mutant that has been engineered to selectively target tumors with deregulated cell cycle and apoptosis pathways. AdΔΔ potentiates apoptotic cell death induced by drugs, including mitoxantrone and docetaxel, which are commonly used to treat prostate cancer. Here, we demonstrate that AdΔΔ can also interact synergistically with dietary phytochemicals known to have anti-cancer activities, without incurring the toxic side effects of chemodrugs. Curcumin, genistein, epigallocatechin-gallate, equol, and resveratrol efficiently killed both androgen-receptor positive (22Rv1) and negative cell lines (PC-3, DU145) in combination with adenoviral mutants. Synergistic cell killing was demonstrated with wild-type virus (Ad5) and AdΔΔ in combination with equol and resveratrol. EC(50) values for both phytochemicals and viruses were reduced three- to eightfold in all three combination-treated cell lines. The most potent efficacy was achieved in the cytotoxic drug- and virus-insensitive PC-3 cells, both in vitro and in vivo, while cell killing in normal bronchial epithelial cells was not enhanced. Although equol and resveratrol induced only low levels of apoptosis when administered alone, in combination with wild-type virus or AdΔΔ, the level of apoptotic cell death was significantly increased in PC-3 and DU145 cells. In vivo studies using suboptimal doses of AdΔΔ and equol or resveratrol, showed reduced tumor growth without toxicity to normal tissue. These findings identify novel functions for AdΔΔ and phytochemicals in promoting cancer cell killing and apoptosis, suggesting the use of these natural nontoxic compounds might be a feasible and currently unexploited anti-cancer strategy.
Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London
Research funded by:


Price AJ, Allen NE, Appleby PN, et al.
Insulin-like growth factor-I concentration and risk of prostate cancer: results from the European Prospective Investigation into Cancer and Nutrition.
Cancer Epidemiol Biomarkers Prev. 2012; 21(9):1531-41 [PubMed]
BACKGROUND: High circulating insulin-like growth factor-I (IGF-I) concentrations have been associated with increased risk for prostate cancer in several prospective epidemiological studies. In this study, we investigate the association between circulating IGF-I concentration and risk of prostate cancer over the long term in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.
METHODS: In a nested case-control design, 1,542 incident prostate cancer cases from eight European countries were individually matched to 1,542 controls by study center, age at recruitment, duration of follow-up, time of day, and duration of fasting at blood collection. Conditional logistic regression models were used to calculate risk for prostate cancer associated with IGF-I concentration, overall and by various subgroups.
RESULTS: Circulating IGF-I concentration was associated with a significant increased risk for prostate cancer [OR for highest vs. lowest quartile, 1.69; 95% confidence interval (CI), 1.35-2.13; P(trend) = 0.0002]. This positive association did not differ according to duration of follow-up [ORs for highest vs. lowest quartile were 2.01 (1.35-2.99), 1.37 (0.94-2.00), and 1.80 (1.17-2.77) for cancers diagnosed <4, 4-7, and >7 years after blood collection, respectively (P(heterogeneity) = 0.77)] or by stage, grade, and age at diagnosis or age at blood collection (all subgroups P(heterogeneity) >0.05).
CONCLUSION: In this European population, high circulating IGF-I concentration is positively associated with risk for prostate cancer over the short and long term.
IMPACT: As IGF-I is the only potentially modifiable risk factor so far identified, research into the effects of reducing circulating IGF-I levels on subsequent prostate cancer risk is warranted.
Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford
Research funded by:


Van Hemelrijck M, Drevin L, Holmberg L, et al.
Primary cancers before and after prostate cancer diagnosis.
Cancer. 2012; 118(24):6207-16 [PubMed]
BACKGROUND: The occurrence of multiple cancers may indicate common etiology; and, although some studies have investigated the risk of second primary cancers after prostate cancer (PCa), there are no studies on cancers before PCa.
METHODS: The PCBaSe Sweden database is based on the National Prostate Cancer Register (NPCR), which covers >96% of PCa cases. The authors estimated the prevalence and cumulative incidence of different cancers before and after PCa diagnosis in 72,613 men according to PCa treatment and disease stage in PCBaSe and their matched comparison cohort of men who were free of PCa.
RESULTS: In total, 6829 men were diagnosed with another primary cancer before their PCa diagnosis, including 138 men at the time of PCa diagnosis and 5230 men were diagnosed after PCa diagnosis. Cancer of the bladder or colon and nonmelanoma of the skin were the 3 most frequently observed cancers before and after PCa diagnosis. At the time of PCa diagnosis, the prevalence of these 3 cancers was 1.94% for bladder cancer, 1.08% for colon cancer, and 1.08% for nonmelanoma skin cancer, compared with 1.30%, 0.96%, and 1.03%, respectively, for the matched comparison cohort. Five years after PCa diagnosis, the difference in incidence proportion between PCa men and their comparison cohort was 7 ‰ (95% CI, 5.6 ‰-8.5 ‰), 1.3 ‰ (0 ‰-2.6 ‰), and 1.6 ‰ (0.6 ‰-2.6 ‰) for these 3 cancers, respectively. From a uro-oncologic point of view, it is interesting to note that the prevalence of kidney cancer at the time of PCa diagnosis was 0.42% compared with 0.28% for the matched comparison cohort.
CONCLUSIONS: Approximately 17% of all PCa occurred in combination with another primary cancer (before or after PCa diagnosis). Detection bias probably explains part of this observation, but further investigations are required to assess possible underlying mechanisms.
Cancer Epidemiology Group, Division of Cancer Studies, School of Medicine, King's College London, London
Research funded by:


Hurst R, Hooper L, Norat T, et al.
Selenium and prostate cancer: systematic review and meta-analysis.
Am J Clin Nutr. 2012; 96(1):111-22 [PubMed]
BACKGROUND: Prostate cancer is a growing public health problem. Several human studies have shown a potentially protective effect of selenium, but the conclusions from published reports are inconsistent.
OBJECTIVE: The objective was to examine the evidence for relations between selenium intake, selenium status, and prostate cancer risk.
DESIGN: This was a systematic review and meta-analysis of randomized controlled trials, case-control studies, and prospective cohort studies. The World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project database was searched up to September 2010. The studies included reported measurements of selenium intake or status (plasma, serum, or toenail selenium), assessments of prostate cancer cases (number of events), and the RR in the adult population. Meta-analyses were performed, and study quality, heterogeneity, and small study effects were assessed. Dose-response meta-analyses were used, with restricted cubic splines and fractional polynomials for nonlinear trends, to investigate the association between selenium status and prostate cancer risk.
RESULTS: Twelve studies with a total of 13,254 participants and 5007 cases of prostate cancer were included. The relation between plasma/serum selenium and prostate cancer in a nonlinear dose-response meta-analysis showed that the risk decreased with increasing plasma/serum selenium up to 170 ng/mL. Three high-quality studies included in the meta-analysis of toenail selenium and cancer risk indicated a reduction in prostate cancer risk (estimated RR: 0.29; 95% CI: 0.14, 0.61) with a toenail selenium concentration between 0.85 and 0.94 μg/g.
CONCLUSION: The relation between selenium status and decreased prostate cancer risk was examined over a relatively narrow range of selenium status; further studies in low-selenium populations are required.
Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, Norfolk


Turney BW, Kerr M, Chitnis MM, et al.
Depletion of the type 1 IGF receptor delays repair of radiation-induced DNA double strand breaks.
Radiother Oncol. 2012; 103(3):402-9 [PubMed]
BACKGROUND AND PURPOSE: IGF-1R depletion sensitizes prostate cancer cells to ionizing radiation and DNA-damaging cytotoxic drugs. This study investigated the hypothesis that IGF-1R regulates DNA double strand break (DSB) repair.
METHODS: We tested effects of IGF-1R siRNA transfection on the repair of radiation-induced DSBs by immunoblotting and immunofluorescence for γH2AX, and pulsed-field gel electrophoresis. Homologous recombination (HR) was quantified by reporter assays, and cell cycle distribution by flow cytometry.
RESULTS: We confirmed that IGF-1R depletion sensitized DU145 and PC3 prostate cancer cells to ionizing radiation. DU145 control transfectants resolved radiation-induced DSBs within 24 h, while IGF-1R depleted cells contained 30-40% unrepaired breaks at 24 h. IGF-1R depletion induced significant reduction in DSB repair by HR, although the magnitude of the repair defect suggests additional contributory factors. Radiation-induced G2-M arrest was attenuated by IGF-1R depletion, potentially suppressing cell cycle-dependent processes required for HR. In contrast, IGF-1R depletion induced only minor radiosensitization in LNCaP cells, and did not influence repair. Cell cycle profiles were similar to DU145, so were unlikely to account for differences in repair responses.
CONCLUSIONS: These data indicate a role for IGF-1R in DSB repair, at least in part via HR, and support use of IGF-1R inhibitors with DNA damaging cancer treatments.
Department of Oncology Laboratories, Weatherall Institute of Molecular Medicine, Oxford
Research funded by:


Poludniowski GG, Evans PM, Webb S
Cone beam computed tomography number errors and consequences for radiotherapy planning: an investigation of correction methods.
Int J Radiat Oncol Biol Phys. 2012; 84(1):e109-14 [PubMed]
PURPOSE: The potential of keV cone beam computed tomography (CBCT) for guiding adaptive replanning is well-known. There are impediments to this, one being CBCT number accuracy. The purpose of this study was to investigate CBCT number correction methods and the affect of residual inaccuracies on dose deposition. Four different correction strategies were applied to the same patient data to compare performance and the sophistication of correction-method needed for acceptable dose errors.
METHODS AND MATERIALS: Planning CT and CBCT reconstructions were used for 12 patients (6 brain, 3 prostate, and 3 bladder cancer patients). All patients were treated using Elekta linear accelerators and XVI imaging systems. Two of the CBCT number correction methods investigated were based on an algorithm previously proposed by the authors but only previously applied to phantoms. Two further methods, based on an approach previously suggested in the research literature, were also examined. Dose calculations were performed using scans of a "worst" subset of patients using the Pinnacle³ version 9.0 treatment planning system and the patients' clinical plans.
RESULTS: All mean errors in CBCT number were <50 HU, and all correction methods performed well or adequately in dose calculations. The worst single dose discrepancy identified for any of the examined methods or patients was 3.0%. Mean errors in the doses to treatment volumes or organs at risk were negatively correlated with the mean error in CT number. That is, a mean CT number that was too large, averaged over the entire CBCT volume, implied an underdosing in a volume-of-interest and vice versa.
CONCLUSIONS: Results suggest that (1) the correction of CBCT numbers to within a mean error of 50 HU in the scan volume provides acceptable discrepancies in dose (<3%) and (2) this is achievable with even quite unsophisticated correction methods.
Joint Department of Physics, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, Surrey
Research funded by:


Darrington RS, Campa VM, Walker MM, et al.
Distinct expression and activity of GSK-3α and GSK-3β in prostate cancer.
Int J Cancer. 2012; 131(6):E872-83 [PubMed]
Glycogen synthase kinase (GSK-3) is upregulated in many types of tumor, including prostate cancer. GSK-3 inhibitors reduce prostate tumor cell growth; however, it is not clear if both isoforms, GSK-3α and GSK-3β, are involved. Here, we compared their expression in prostate tumors and used gene silencing to study their functions in 22Rv1 prostate cancer cells. Compared to normal prostate, GSK-3α and GSK-3β were upregulated in 25/79 and 24/79 cases of prostate cancer, respectively, with GSK-3α elevated in low Gleason sum score tumors and GSK-3β expressed in high Gleason tumors, and both isoforms correlating with high expression of the androgen receptor (AR). Gene silencing of GSK-3α and, to a lesser extent, GSK-3β reduced AR transcriptional activity. In addition, silencing of GSK-3β, but not GSK-3α, reduced Akt phosphorylation. Acute and chronic silencing of either isoform reduced 22Rv1 growth in colony formation assays; however, this did not correlate with effects on AR activity. The GSK-3 inhibitor CHIR99021 reduced 22Rv1 colony formation by 50% in normal growth medium and by 15% in hormone-depleted medium, suggesting that GSK-3 is required both for hormone-dependent and hormone-independent proliferation. In addition, CHIR99021 enhanced growth inhibition by the AR antagonists bicalutamide and MDV3100. Finally, expression of GSK3A and GSK3B mRNAs correlated with a gene expression signature for androgen-regulated genes. Our observations highlight the importance of the GSK-3/AR signaling axis in prostate cancer and support the case for development of isoform-specific GSK-3 inhibitors and their use, in combination with AR antagonists, to treat patients with prostate cancer.
Department of Surgery and Cancer, Imperial College London, London


Groom HC, Warren AY, Neal DE, Bishop KN
No evidence for infection of UK prostate cancer patients with XMRV, BK virus, Trichomonas vaginalis or human papilloma viruses.
PLoS One. 2012; 7(3):e34221 [PubMed] Article available free on PMC after 01/09/2013
The prevalence of specific infections in UK prostate cancer patients was investigated. Serum from 84 patients and 62 controls was tested for neutralisation of xenotropic murine leukaemia virus-related virus (XMRV) Envelope. No reactivity was found in the patient samples. In addition, a further 100 prostate DNA samples were tested for XMRV, BK virus, Trichomonas vaginalis and human papilloma viruses by nucleic acid detection techniques. Despite demonstrating DNA integrity and assay sensitivity, we failed to detect the presence of any of these agents in DNA samples, bar one sample that was weakly positive for HPV16. Therefore we conclude that these infections are absent in this typical cohort of men with prostate cancer.
Division of Virology, MRC National Institute for Medical Research, London
Research funded by:


Tsilidis KK, Travis RC, Appleby PN, et al.
Interactions between genome-wide significant genetic variants and circulating concentrations of insulin-like growth factor 1, sex hormones, and binding proteins in relation to prostate cancer risk in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium.
Am J Epidemiol. 2012; 175(9):926-35 [PubMed] Article available free on PMC after 01/09/2013
Genome-wide association studies (GWAS) have identified many single nucleotide polymorphisms (SNPs) associated with prostate cancer risk. There is limited information on the mechanistic basis of these associations, particularly about whether they interact with circulating concentrations of growth factors and sex hormones, which may be important in prostate cancer etiology. Using conditional logistic regression, the authors compared per-allele odds ratios for prostate cancer for 39 GWAS-identified SNPs across thirds (tertile groups) of circulating concentrations of insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), testosterone, androstenedione, androstanediol glucuronide, estradiol, and sex hormone-binding globulin (SHBG) for 3,043 cases and 3,478 controls in the Breast and Prostate Cancer Cohort Consortium. After allowing for multiple testing, none of the SNPs examined were significantly associated with growth factor or hormone concentrations, and the SNP-prostate cancer associations did not differ by these concentrations, although 4 interactions were marginally significant (MSMB-rs10993994 with androstenedione (uncorrected P = 0.008); CTBP2-rs4962416 with IGFBP-3 (uncorrected P = 0.003); 11q13.2-rs12418451 with IGF-1 (uncorrected P = 0.006); and 11q13.2-rs10896449 with SHBG (uncorrected P = 0.005)). The authors found no strong evidence that associations between GWAS-identified SNPs and prostate cancer are modified by circulating concentrations of IGF-1, sex hormones, or their major binding proteins.
Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford
Research funded by:


Richards J, Lim AC, Hay CW, et al.
Interactions of abiraterone, eplerenone, and prednisolone with wild-type and mutant androgen receptor: a rationale for increasing abiraterone exposure or combining with MDV3100.
Cancer Res. 2012; 72(9):2176-82 [PubMed]
Prostate cancer progression can be associated with androgen receptor (AR) mutations acquired following treatment with castration and/or an antiandrogen. Abiraterone, a rationally designed inhibitor of CYP17A1 recently approved for the treatment of docetaxel-treated castration-resistant prostate cancer (CRPC), is often effective, but requires coadministration with glucocorticoids to curtail side effects. Here, we hypothesized that progressive disease on abiraterone may occur secondary to glucocorticoid-induced activation of mutated AR. We found that prednisolone plasma levels in patients with CRPC were sufficiently high to activate mutant AR. Mineralocorticoid receptor antagonists, such as spironolactone and eplerenone that are used to treat side effects related to mineralocorticoid excess, can also bind to and activate signaling through wild-type or mutant AR. Abiraterone inhibited in vitro proliferation and AR-regulated gene expression of AR-positive prostate cancer cells, which could be explained by AR antagonism in addition to inhibition of steroidogenesis. In fact, activation of mutant AR by eplerenone was inhibited by MDV3100, bicalutamide, or greater concentrations of abiraterone. Therefore, an increase in abiraterone exposure could reverse resistance secondary to activation of AR by residual ligands or coadministered drugs. Together, our findings provide a strong rationale for clinical evaluation of combined CYP17A1 inhibition and AR antagonism.
Section of Medicine, The Institute of Cancer Research, Sutton, Surrey
Research funded by:


Shamash J, Jacob J, Agrawal S, et al.
Whole blood stem cell reinfusion and escalated dose melphalan in castration-resistant prostate cancer: a phase 1 study.
Clin Cancer Res. 2012; 18(8):2352-9 [PubMed]
PURPOSE: Nontaxane-based chemotherapeutic options in castrate-resistant prostate cancer (CRPC) are limited despite the long natural history of the disease. We carried out a phase 1 dose-escalation study of the alkylating agent melphalan with autologous stem cell transplantation, comparing rapid changes in circulating tumor cells (CTC) and prostate-specific antigen (PSA) as a measure of response.
EXPERIMENTAL DESIGN: Cohorts of individuals with advanced CRPC received high-dose intravenous melphalan, and autologous blood was returned to patients during treatment. The efficacy endpoints were the PSA reduction rate, CTC response, survival parameters, toxicity and whether reinduction of endocrine sensitivity occurred.
RESULTS: Twenty-four patients were recruited. Dose escalation was feasible with the highest dose cohort being reached. Of 23 individuals evaluable for response, 16 had a PSA response of more than 30%; of 11 patients with soft tissue disease, 4 achieved a partial response and 7 had stable disease. Patients with CTC counts that decreased to less than 5 within 2 weeks from the start of therapy had a longer overall survival (30.6 months vs. 15.3 months, P = 0.03) Treatment was associated with myelosuppression and frequent hospitalizations. In 20 patients after the study, hormone therapy was reintroduced when PSA increased again; response rates were high.
CONCLUSIONS: Autologous transplantation following high-dose alkylating agent chemotherapy induces responses but proved toxic, although dose escalation proved possible. The possibility of using CTCs to identify responders at two weeks may be used to justify such an intensive approach. Many individuals went on to further respond to both docetaxel and hormonal therapy.
Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, London


Morgan VA, Riches SF, Giles S, et al.
Diffusion-weighted MRI for locally recurrent prostate cancer after external beam radiotherapy.
AJR Am J Roentgenol. 2012; 198(3):596-602 [PubMed]
OBJECTIVE: The objectives of our study were to establish the apparent diffusion coefficients (ADCs) of tumor and nontumor irradiated tissues in patients with suspected postradiation recurrence of prostate cancer and to determine the sensitivity and specificity of a combination of T2-weighted and diffusion-weighted imaging (DWI) for detecting local recurrence.
MATERIALS AND METHODS: Twenty-four patients with rising prostate-specific antigen levels after having completed radiation therapy 30-130 months earlier (median, 62 months) underwent endorectal T2-weighted imaging and DWI (b = 0, 100, 300, 500, and 800 s/mm(2)) followed by transrectal ultrasound (TRUS)-guided biopsy. Images were scored prospectively as positive for tumor if a region of low signal intensity on T2-weighted imaging within the prostate corresponded with a focally restricted area on the ADC map. A region of interest (ROI) was drawn around the suspicious lesion on a single slice of the ADC map and a corresponding ROI was drawn around presumed nontumor irradiated peripheral zone and central gland tissues on the opposite side of the prostate. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined against TRUS-guided biopsy reference standard (octant, n = 17; sextant, n = 5; two samples, n = 1; 12 samples, n = 1).
RESULTS: Sixteen of 24 patients (66.7%) had positive histology findings. The median tumor ROI area was 0.37 cm(2) (quartiles, 0.30 and 0.82 cm(2)). The sensitivity, specificity, PPV, and NPV for detecting tumor were 93.8%, 75%, 88.2%, and 85.7%, respectively. A cutoff ADC of 1216 × 10(-6) mm(2)/s could predict tumor with 100% sensitivity and 96% specificity (area under the receiver operating characteristic curve = 0.992).
CONCLUSION: An ADC derived from DWI is a useful adjunct to T2-weighted MRI for detecting local tumor recurrence larger than 0.4 cm(2) within the prostate.
Cancer Research UK Clinical Magnetic Resonance Research Group, Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey
Research funded by:


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