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Kirby M.,Prostate Center | Hirst C.,Astrazeneca | Crawford E.D.,University of Colorado at Denver
International Journal of Clinical Practice | Year: 2011

Background: Castration-resistant prostate cancer (CRPC) is an advanced form of prostate cancer associated with poor survival rates. However, characterisation of the disease epidemiology is hampered by use of varying terminology, definition and disease management. The aim of this review was to conduct a systematic review to provide greater clarity on the sum of the available epidemiologic evidence and to guide future research into the disease prevalence, progression, characteristics and outcome. Methods: Systematic searches of PubMed and Embase were performed in March 2010 to identify relevant observational studies relating to the epidemiology, progression and outcomes of CRPC. Further studies were identified for inclusion in our review through manual searches of the authors' bibliographical databases and the reference lists of the included articles. Results: We identified 12 articles (10 full papers and 2 abstracts) reporting studies that included a total of 71,179 patients observed for up to 12 years for evaluation in our review. Five studies looked at the prevalence of CRPC in patients with prostate cancer. Together, the data indicate that 10-20% of prostate cancer patients develop CRPC within approximately 5 years of follow-up. Two studies reported the prevalence of bone metastases present at diagnosis of CRPC. Together, ≥ 84% were shown to have metastases at diagnosis. Of those patients with no metastases present at diagnosis of CRPC, 33% could expect to develop them within 2 years. The median survival of patients with CRPC was reported in five studies, with values varying from 9 to 30 months. A pooled, sample-weighted survival estimate calculated from the survival data included in this review is 14 months. Very few studies that met our inclusion criteria evaluated treatment patterns in CRPC. One study reported that only 37% of patients with CRPC received chemotherapy, with the remainder receiving only steroids and supportive care. The most common palliative therapies administered to patients with skeletal symptoms were radiotherapy, radionuclide therapy, bisphosphonates and opioids. Conclusions: This review highlights the poor prognosis of patients with CRPC, and demonstrates a survival of 9-13 months in those patients with metastatic CRPC. Furthermore, progression to CRPC is associated with deterioration in quality of life, and few therapeutic options are currently available to patients with CRPC. However, epidemiologic study of these patients is hampered by differing terminology, definitions and treatment paradigms. Our review highlights the need for further well-designed, epidemiological studies of CRPC, using standardised definitions and methods. © 2011 Blackwell Publishing Ltd.


Speakman M.,Musgrove Park Hospital | Kirby R.,Prostate Center | Doyle S.,Glaxosmithkline | Doyle S.,University of Oxford | Ioannou C.,Glaxosmithkline
BJU International | Year: 2015

Key Messages Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) can be bothersome and negatively impact on a patient's quality of life (QoL). As the prevalence of LUTS/BPH increases with age, the burden on the healthcare system and society may increase due to the ageing population. This review unifies literature on the burden of LUTS/BPH on patients and society, particularly in the UK. LUTS/BPH is associated with high personal and societal costs, both in direct medical costs and indirect losses in daily functioning, and through its negative impact on QoL for patients and partners. LUTS/BPH is often underdiagnosed and undertreated. Men should be encouraged to seek medical advice for this condition and should not accept it as part of ageing, while clinicians should be more active in the identification and treatment of LUTS/BPH. To assess the burden of illness and unmet need arising from lower urinary tract symptoms (LUTS) presumed secondary to benign prostatic hyperplasia (BPH) from an individual patient and societal perspective with a focus on the UK. Embase, PubMed, the World Health Organization, the Cochrane Database of Systematic Reviews and the York Centre for Reviews and Dissemination were searched to identify studies on the epidemiological, humanistic or economic burden of LUTS/BPH published in English between October 2001 and January 2013. Data were extracted and the quality of the studies was assessed for inclusion. UK data were reported; in the absence of UK data, European and USA data were provided. In all, 374 abstracts were identified, 104 full papers were assessed and 33 papers met the inclusion criteria and were included in the review. An additional paper was included in the review upon a revision in 2014. The papers show that LUTS are common in the UK, affecting ≈3% of men aged 45-49 years, rising to >30% in men aged ≥85 years. European and USA studies have reported the major impact of LUTS on quality of life of the patient and their partner. LUTS are associated with high personal and societal costs, both in direct medical costs and indirect losses in daily functioning. While treatment costs in the UK are relatively low compared with other countries, the burden on health services is still substantial. LUTS associated with BPH is a highly impactful condition that is often undertreated. LUTS/BPH have a major impact on men, their families, health services and society. Men with LUTS secondary to BPH should not simply accept their symptoms as part of ageing, but should be encouraged to consult their physicians if they have bothersome symptoms. © 2014 The Authors. BJU International © 2014 BJU International.


Rocha J.,McGill University | Zouanat F.Z.,McGill University | Zoubeidi A.,Prostate Center | Hamel L.,McGill University | And 5 more authors.
Molecular and Cellular Endocrinology | Year: 2013

Castrate-resistant prostate cancer (CRPC) is invariably lethal and still poorly understood. IL-6/pSTAT3 appears critical as elevated IL-6 and pSTAT3 correlate with CRPC and poor prognosis. We previously reported on the Fer tyrosine kinase being an integral component of the IL-6 pathway in PC by controlling STAT3. Since IL-6 also controls androgen receptor (AR) signaling via pSTAT3, we tested if Fer participates in this cross-talk. We report for the first time that in addition to STAT3, Fer is required for IL-6 mediated AR activation by phosphorylating AR tyrosine 223 and binding via its SH2 domain. Fer controls IL-6 induced growth response and PSA expression, while modestly contributing to EGF and IGF-1 effects. Finally, Fer, AR and pSTAT3 co-localize in the PC cell nucleus, including in prostate tissues from CRPC patients. Altogether these findings support a Fer contribution to aberrant AR signaling via pSTAT3 cross-talks during CRPC progression. © 2013 Elsevier Ireland Ltd.


Hackett G.,Heartlands Hospital | Hackett G.,University of Bedfordshire | Kirby M.,University of Bedfordshire | Kirby M.,Prostate Center | And 2 more authors.
International Journal of Endocrinology | Year: 2014

Low levels of testosterone are manifested by erectile dysfunction, reduced sexual desire, and loss of morning erections with increasing numbers of men are being diagnosed and require treatment. The prevalence rates of testosterone deficiency vary according to different studies but may be as high as 40% in populations of patients with type 2 diabetes. There is increasing evidence that testosterone deficiency is associated with increased cardiovascular and all-cause mortality. Screening for low testosterone is recommended in a number of high risk groups including those with type 2 diabetes and metabolic syndrome. There are recent data to suggest that testosterone replacement therapy may reduce cardiovascular mortality as well as improving multiple surrogate markers for cardiovascular events. Specific clinical trials of testosterone replacement therapy are needed in selected populations but in the meantime we must treat patients based on the best current evidence. © 2014 G. Hackett et al.


Robinson D.,King's College | Cardozo L.,King's College | Milsom I.,Gothenburg University | Pons M.E.,University of Barcelona | And 3 more authors.
Neurourology and Urodynamics | Year: 2014

Estrogens are known to have a major role in the function of the lower urinary tract although the role of exogenous estrogen replacement therapy in the management of women with lower urinary tract dysfunction remains controversial. Whilst for many years systemic and vaginal estrogen therapy was felt to be beneficial in the treatment of lower urinary and genital tract symptoms this evidence has recently been challenged by large epidemiological studies investigating the use of systemic hormone replacement therapy. Consequently the role of estrogen in the management of postmenopausal women with Overactive Bladder (OAB) remains uncertain. In addition the evidence base regarding the use of exogenous estrogen therapy has changed significantly over the last decade and has led to a major changes in current clinical practice. The aim of this article is to review the evidence for the role of estrogen therapy in the management of OAB focusing on current knowledge with regard to both systemic and local estrogen therapy as well as investigating the emerging role of combination therapy with antimuscarinic agents. © 2013 Wiley Periodicals, Inc.


Goldstraw M.A.,Barnet and Chase Farm NHS Trust | Challacombe B.J.,Guys and St Thomas NHS Foundation | Patil K.,St Peters Hospital | Amoroso P.,Prostate Center | And 3 more authors.
Prostate Cancer and Prostatic Diseases | Year: 2012

Robot-assisted radical prostatectomy (RARP) is the most commonly performed robotic procedure worldwide and is firmly established as a standard treatment option for localised prostate cancer. Part of the explanation for the rapid uptake of RARP is the reported gentler learning curve compared with the challenges of laparoscopic radical prostatectomy (LRP). However, robotic surgery is still fraught with potential difficulties and avoiding complications while on the steepest part of the learning curve is critical. Furthermore, as surgeons progress there is a tendency to take on increasingly complex cases, including patients with difficult anatomy and prior surgery, and these cases present a unique challenge. Significant intra-abdominal adhesions may be identified following open surgery, or dense periprostatic inflammation may be encountered following TURP; large prostate gland size and median lobes may alter bladder neck anatomy, making difficult subsequent urethro-vesical anastomosis. Even experienced robotic surgeons will be challenged by salvage RARP. Approaching these problems in a structured manner allows many of the problems to be overcome. We discuss some of the specific techniques to deal with these potential difficulties and highlight ways to avoid making serious mistakes. © 2012 Macmillan Publishers Limited All rights reserved.


Patel U.,Prostate Center | Dasgupta P.,Prostate Center | Amoroso P.,Prostate Center | Challacombe B.,Prostate Center | And 2 more authors.
BJU International | Year: 2012

Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Septicaemia is the most frequent cause of hospitalization after transtrectal prostate biopsy; fatalities have been reported and the incidence is on the rise. This study shows that men with a history of recent international travel or antibiotic use have up to four times increased risk of septicaemia and hospitalization. When they do occur, infections are usually due to multi-resistant E coli and additional care, e.g. delay before biopsy, different antibiotic prophylaxis or transperineal biopsy, should be considered in these cases. OBJECTIVE To study the infection rate after prostate biopsy in those who have travelled overseas or used antibiotics in the 4 weeks before biopsy. PATIENTS AND METHODS A total of 316 men with a mean (range) age of 61 (45-85) years were studied. All had undergone transrectal ultrasonography (TRUS)-guided prostate biopsy after standard antibiotic prophylaxis. Before their biopsy the patients were risk stratified and a history of recent international travel or antibiotic use was recorded. Those who suffered sufficiently severe infection/sepsis so as to require hospitalization were identified at the end of the study period. The characteristics of these patients and the types of infections were explored and the relative risk (RR) of infection after recent travel or antibiotic use was calculated. RESULTS Of the 316 men, 16 were hospitalized with infection. The group with (n= 16) and without (n= 300) infection were equivalent in age, prostate-specific antigen level, disease status and number of biopsy cores taken. Either recent travel or antibiotic use were independent risk factors for infection [travel: 8/16 vs 76/300; P= 0.04; RR 2.7 and antibiotic use: 4/16 vs 20/300; P= 0.025; RR 4]. There was no significant pattern in the countries visited or the type of antibiotic used. Culture results were positive in 10/16 men, and all cultures grew multiresistant Escherichia coli. The strains were uniformly resistant to ciprofloxacin and amoxycillin, and variably resistant to gentamicin and co-amoxiclav, but nearly all were sensitive to meropenem. All patients made a full recovery after antibiotic and supportive treatment. CONCLUSIONS Either recent international travel or antibiotic use are independent risk factors for severe infection after TRUS-guided prostate biopsy. When infection does occur it should be treated aggressively as the causative agent is usually a multiresistant E. coli. © 2011 BJU INTERNATIONAL.


Tunn U.W.,Prostate Center | Gruca D.,AbbVie Deutschland GmbH and Co | Bacher P.,AbbVie
Clinical Interventions in Aging | Year: 2013

For nearly three decades, gonadotropin-releasing hormone (GnRH) agonists, particularly leuprorelin acetate (LA), have served as an important part of the treatment armamentarium for prostate cancer. The introduction of LA depot formulations provided a significant improvement in the acceptance of this therapy; however, their indicated treatment duration of 1 to 4 months was still not long enough to satisfy all medical needs. For this reason some manufacturers developed new injectable formulations that provide testosterone suppression for 6 months. This review article assesses key publications in order to compare these long-acting, commercially available, LA depot formulations and their clinical performance. The literature search identified 14 publications; by excluding reviews, duplications, and non-English articles, only three original papers describing clinical trial remained for review: two focused on microsphere-based LA formulations with either a 30 mg or 45 mg dose and one focused on a gel-based leuprorelin acetate with a 45 mg dose. All products were tested in individual clinical trials and have demonstrated their efficacy and safety. © 2013 Tunn et al, publisher and licensee Dove Medical Press Ltd.


Kirby R.,Prostate Center
Future Oncology | Year: 2013

Roger Kirby speaks to Natasha Galukande, Assistant Commissioning Editor. Roger Kirby graduated in Medical Sciences from Cambridge University (Cambridge, UK) in 1972. He then trained in surgery at University of London (London, UK) before specializing in urology. Kirby is currently the director of The Prostate Centre (London, UK), which he established in 2005. Kirby is the founding editor of the journal Prostate Cancer and Prostate Diseases, in addition to being the associate editor of the British Journal of Urology International, and founding editor of Trends in Urology and Men's Health. He has written over 60 books, published over 300 papers and performed over 2000 radical prostatectomies. In 2005, Kirby was awarded the St Peter's Medal by the British Association of Urological Surgeons. Kirby has also helped to raise over £3 million as trustee and secretary of the Urological Foundation and former chair of Prostate UK. © 2013 Future Medicine Ltd.


Kirby R.,Prostate Center | Fitzpatrick J.M.,University College Dublin
BJU International | Year: 2012

What's known on the subject? and What does the study add? Due to the fear of missing clinically significant cancer, it is often uncertain whether a repeat biopsy should be performed in men with ≥1 prior negative prostate biopsies but persistent suspicion of prostate cancer. However, the repeat biopsy may again be negative and a biopsy may be associated with anxiety, discomfort and complications (resulting in hospitalisation in 4.1% of men). This review discusses strategies to optimise repeat biopsy procedures in order to better predict the biopsy outcome. Optimising repeat biopsy procedures include adjusting the location and number of cores and the use of MRI to detect suspicious areas. The use of diagnostic markers, e.g. (Prostate CAncer) gene 3, which is predictive of biopsy outcome, can aid in guiding repeat biopsy decisions and reduce the number of unnecessary and uncomfortable biopsies. To review strategies to optimise repeat biopsy procedures and to better predict the biopsy outcome. As it is often uncertain whether a repeat biopsy should be performed in men with ≥1 previous negative prostate biopsies but persistent suspicion of prostate cancer. The repeat biopsy may also be negative and a biopsy may be associated with anxiety, discomfort and occasionally (severe) complications. A search in PubMed was performed to find English language original and review articles related to repeat prostate biopsies. Strategies to optimise repeat biopsy procedures include applying the appropriate indications and adjusting the location and number of biopsy cores. The PROGENSA™ Prostate CAncer gene 3 (PCA3) Assay is a highly prostate cancer-specific test. A higher PCA3 Score corresponds with an increased probability of a positive repeat biopsy and including the PCA3 Score in multivariate models significantly increased their predictive accuracy for predicting repeat biopsy outcome. The PCA3 Score seems also to be predictive of future biopsy outcome. In clinical practice it is often uncertain whether a prostate biopsy should be repeated or not. Optimising repeat biopsy procedures and the use of diagnostic markers, such as PCA3, can increase the probability of a positive repeat biopsy and reduce the number of unnecessary and uncomfortable biopsies © 2011 BJU INTERNATIONAL.

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