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Aims The National Prostate Cancer Audit (NPCA) started in April 2013 with the aim of assessing the process of care and its outcomes in men diagnosed with prostate cancer in England and Wales. One of the key aims of the audit was to assess the configuration and availability of specialist prostate cancer services in England. Materials and methods In 2014, the NPCA undertook an organisational survey of all 143 acute National Health Service (NHS) Trusts and 48 specialist multidisciplinary team (MDT) hubs cross England. Questionnaires established the availability and location of core diagnostic, treatment and patient-centred support services for the management of non-metastatic prostate cancer in addition to specific diagnostic and treatment procedures that reflect the continuing evolution of prostate cancer management, such as high-intensity focused ultrasound (HIFU) and stereotactic body radiotherapy. Results The survey received a 100% response rate. The results showed considerable geographical variation with respect to the availability of core treatment modalities, the size of the target population and catchment areas served by specialist MDT hubs, as well as in the uptake of additional procedures and services. Specifically there are gaps in the availability of core radiotherapy procedures; high dose rate and low dose rate brachytherapy are available in 44% and 75% of specialist MDTs, respectively. By comparison, there seems to be a relative ‘over-penetration' of surgical innovation, with 67% of specialist MDTs providing robotic-assisted laparoscopic prostatectomy and 21% HIFU. There is also evidence of increased centralisation of core surgical procedures and regional inequity in the availability of surgical innovation across England. Conclusions The organisational survey of the NPCA has provided a comprehensive assessment of the structure and function of specialist MDTs in England and the availability of prostate cancer procedures and services. As part of the prospective audit, the NPCA will assess the effect of the availability of prostate cancer services on access regionally and subsequent outcomes of care according to evidence-based guidelines.

Prior to 2004, the uro-oncology community viewed the management of advanced or metastatic prostate cancer with an air of resigned nihilism. Now, the range of therapeutic options available is the subject of ongoing debate and the British Uro-oncology Group (BUG) is collating oncologist opinions on the future management of castration-sensitive disease. Historically, treatment for metastatic prostate cancer was limited to androgen deprivation therapy (ADT) with the aims of delaying disease progression and palliating symptoms. Patients invariably progressed, developing castration-resistant disease with limited effective therapeutic options. This article is protected by copyright. All rights reserved.

In men with locally advanced/high-risk prostate cancer, there is an ongoing challenge to achieve improved results. Dose escalation studies using three-dimensional conformal radiotherapy (3D-CRT) or intensity modulated radiation therapy (IMRT) have shown benefit particularly in the intermediate and poor risk groups of patients. Of concern, however, is the increase in documented rectal toxicity. High-dose rate brachytherapy (HDR-BT) as a boost in combination with external beam radiotherapy (EBRT) is an alternative strategy of dose escalation that can potentially achieve an even higher biological equivalent dose (BED) to the tumour. The results so far are very encouraging for men with poor prognosis disease. Moreover the technique is associated with very low rates of acute and late toxicity.

Background and purpose The ongoing Early Prostate Cancer (EPC) programme is assessing bicalutamide (‘Casodex') 150mg, either alone or as adjuvant to treatment of curative intent, in patients with localised or locally advanced prostate cancer ( n =8113). This paper presents an exploratory analysis of the subgroup of the EPC programme who received radiotherapy with curative intent ( n =1370) in order to determine the efficacy (in terms of progression-free survival [PFS]) and tolerability of bicalutamide 150mg in this setting. Patients and methods 1370 patients with T1-4, M0, any N prostate cancer received bicalutamide 150mg or placebo adjuvant to radiotherapy of curative intent. This analysis was undertaken at median 5.3 years' follow-up. Results In patients with locally advanced disease ( n =305), bicalutamide adjuvant to radiotherapy significantly increased PFS by 53% (event-time ratio 1.53; 95% confidence intervals [CI] 1.16, 2.02) compared with placebo and reduced the risk of disease progression by 42% (hazard ratio [HR] 0.58; 95% CI 0.41, 0.84; P =0.00348). In these patients, objective progression was experienced by 33.5% of those randomised to bicalutamide versus 48.6% for those randomised to placebo. The between-group difference in patients with localised disease ( n =1065) failed to reach statistical significance (HR 0.80; 95% CI 0.62, 1.03; P =0.088). The most common adverse events were breast pain (74.8%) and gynaecomastia (66.6%), which were mild to moderate in >90% of cases. Conclusions Bicalutamide 150mg/day given as adjuvant to radiotherapy significantly improved PFS in patients with locally advanced prostate cancer. For patients with localised disease, the results at this stage from the radiotherapy subgroup and the overall EPC programme suggest that adjuvant hormonal therapy is currently not appropriate. There were no unexpected tolerability findings.

In this series, the authors present cases of men being treated with androgen deprivation therapy, and highlight management strategies to prevent and treat associated toxicities. In this third article, the authors consider the management of gynaecomastia and mastalgia. Copyright © 2013 John Wiley & Sons

Cancer patients, particularly the elderly, will often have other conditions that add to their burden of disease. They will also be taking medicines for those diseases that have to be managed alongside cancer treatment. In this article the authors highlight the problem and describe how medicines optimisation can help.

BACKGROUND Although < 1% of men present with prostate-specific antigen (PSA)-negative prostate carcinoma, in that they have serum PSA levels much lower than the tumor burden would suggest, such patients represent a management dilemma. To the authors' knowledge, little information exists in the literature regarding patterns of disease and response to treatment. The authors wished to define the clinical features of this patient group. METHODS The British Association of Urological Surgeons Cancer Registry 2000 and 2001 data bases were used to identify the clinical features and outcome of 33 men with metastatic prostate carcinoma who presented with serum PSA levels < 10 ng/mL. Clinical notes and histopathology were reviewed for each patient. RESULTS Seventeen patients (51%) presented with urinary symptoms and/or pelvic pain, 6% with cachexia and 21% with bone pain. Characteristic bone metastases were present in 81% of patients, similar to the presentation of men with high serum PSA levels. Hypercalcemia was a feature in 9% of patients. Visceral metastases were present in two patients. The median response duration to first-line hormone manipulation was 7 months. No responses were seen in 11 of 13 patients who received second-line hormones or to any third-line treatment. Three of 5 patients who received chemotherapy responded but developed recurrent disease within 8 weeks of treatment cessation. The median overall survival was 12 months. CONCLUSIONS The presentation of patients with treatment-naive PSA-negative metastatic prostate carcinoma is similar to that of patients with high serum PSA levels, but their median survival and response duration to first-line hormone therapy are of much shorter duration. Second-line hormone therapy is ineffective, but early chemotherapy may be beneficial. Hypercalcemia is a particular feature in this group of patients. Cancer 2003. © 2003 American Cancer Society.

The PAD Trial is a prospective, multicenter, randomized clinical study testing whether volunteer, non-medical responders can improve survival from out-of-hospital cardiac arrest (OOH-CA) by using automated external defibrillators (AEDs). These lay volunteers, who have no traditional responsibility to respond to a medical emergency as part of their primary job description, will form part of a comprehensive, integrated community approach to the treatment of OOH-CA. The study is being conducted at 24 field centers in the United States and Canada. Approximately 1000 community units (e.g. apartment or office buildings, gated communities, sports facilities, senior centers, shopping malls, etc.) were randomized to treatment by trained laypersons who will provide either cardiopulmonary resuscitation (CPR) alone or CPR plus use of an AED, while awaiting arrival of the community's emergency medical services responders. The primary endpoint is the number of OOH-CA victims who survive to hospital discharge. Secondary endpoints include neurological status, health-related quality of life (HRQL), cost, and cost-effectiveness. Data collection will last approximately 15 months and is expected to be completed in September 2003.

This report is based on a seminar held during the 8th Annual Meeting of the British Uro-oncology Group in York last September. Hot topics for debate covered in part 2 of this article are: ‘When and how to treat pelvic lymph nodes’ and ‘The significance of PSA in asymptomatic metastatic prostate cancer’. All participants, most of whom were clinical oncologists, were invited to contribute and respond to set questions using a keypad voting system.

This report is based on a seminar held during the 8th Annual Meeting of the British Uro-oncology Group in York last September. Hot topics for debate covered in part 1 of this article are the use of active surveillance for intermediate-risk prostate cancer and cardiovascular risks in the hormonal management of locally advanced prostate cancer. All participants, most of whom were clinical oncologists, were invited to contribute and respond to set questions using a keypad voting system.

Purpose: Photodynamic therapy, using a photosensitizing drug activated by red light, can destroy localized areas of cancer with safe healing and without the cumulative toxicity associated with ionizing radiation. We used photodynamic therapy in a phase I–II study to treat patients with locally recurrent prostate cancer after radiotherapy.Materials and Methods: Patients with an increasing prostate specific antigen (PSA) and biopsy proven local recurrence after radiotherapy were offered photodynamic therapy. Three days after intravenous administration of the photosensitizer meso-tetrahydroxyphenyl chlorin, light was applied using optical fibers inserted percutaneously through perineal needles positioned in the prostate with imaging guidance. Patients were followed with PSA measurements, prostate biopsies, computerized tomography or magnetic resonance imaging and questionnaires on urinary and sexual function.Results: Photodynamic therapy was given to 14 men using high light doses in 13. Treatment was...

Rising prostate-specific antigen (PSA) levels following primary therapy for prostate cancer may cause patients undue anxiety and stress. This paper explores the management of this increasingly common problem. Key issues are identifying the patient at risk of PSA progression, when and how to investigate a rising PSA, and what treatments to consider. Treatment decisions will be influenced by whether disease recurrence is local or systemic (although definitive diagnosis can be difficult) and patient choice. As patients with a rising PSA are generally relatively young and active, the quality of life implications of treatment are important. When hormone therapy is considered, antiandrogen monotherapy offers potential quality of life advantages over castration-based therapies, with recent data showing that the majority of men retain some sexual activity and function on bicalutamide (‘Casodex') 150mg. The cases of three patients with treatment failure, as determined by PSA progression, after primary therapy (radical prostatectomy, radiotherapy or watchful waiting) are presented to illustrate some of the problems associated with managing rising PSA levels. In each case, the patient was still sexually active. Successful outcomes, in terms of patient satisfaction, were achieved with continued observation, salvage local therapy and bicalutamide 150mg therapy, respectively.

Heather A. Payne, Consultant in Clinical Oncology, University College Hospitals, London; Chair of British Uro-oncology Group; David Dearnaley, Professor of Uro-Oncology and Honorary Consultant in Clinical Oncology, Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey; Janis Troup, British Uro-oncology Group Secretariat The first-line and mainstay of medical treatment for advanced prostate cancer is with androgen deprivation therapy in the form of medical castration. These treatments have been shown to reduce the painful symptoms of the disease and also to slow overall cancer progression. However, it is recognised that after a period of time, most prostate cancers will ultimately progress in spite of castrate levels of testosterone (ie serum testosterone

Introduction Because of the lack of published evidence, this study was done to explore the decisions and rationale of uro-oncology consultants regarding the treatment of patients with muscle-invasive bladder cancer who have positive lymph nodes after radical cystectomy (RC) and neoadjuvant chemotherapy (NAC). Materials and Methods An electronic survey was sent to UK pelvic cancer centers regarding: (1) choice of NAC regimen; (2) indications for reimaging; (3) choice and indication of adjuvant chemotherapy (AC) for patients with nodal disease after NAC and RC; (4) choice and indication of chemotherapy regimen if disease continues to progress in patients with advanced bladder cancer; and (5) guidelines used by those surveyed. Results Consultant uro-oncologists from 77% of UK pelvic cancer centers responded, who treated a median of 13 patients per year with NAC before RC. Three cycles of gemcitabine and cisplatin was the most common NAC regimen, with 93% and 67% respondents giving it for downstaging of cN1- and cN2- and 3-positive patients, respectively. Forty-five percent would not give AC after NAC and RC in patients with positive lymph nodes. The patient's performance status, followed by response to NAC were key factors in dictating the use of AC. In the presence of disease progression, 46% of participants would use a taxane. Fifty-two percent of responders do not follow any guidelines. Conclusion In the United Kingdom, the treatment of patients with nodal disease after NAC and RC is variable. There is little evidence on which to base the management of such patients. The creation of national and international guidelines might help clinicians to optimize care for these patients.

In 2010, the International Society of Geriatric Oncology (SIOG) developed treatment guidelines for men with prostate cancer who are older than 70 years old. In 2013, a new multidisciplinary SIOG working group was formed to update these recommendations. The consensus of the task force is that older men with prostate cancer should be managed according to their individual health status, not according to age. On the basis of a validated rapid health status screening instrument and simple assessment, the task force recommends that patients are classed into three groups for treatment: healthy or fit patients who should have the same treatment options as younger patients; vulnerable patients with reversible impairment who should receive standard treatment after medical intervention; and frail patients with non-reversible impairment who should receive adapted treatment.

To examine prostate-specific antigen (PSA) levels after enzalutamide discontinuation to assess whether an antiandrogen withdrawal syndrome (AAWS) exists with enzalutamide.We retrospectively identified 30 consecutive patients with metastatic prostate cancer who were treated with enzalutamide after docetaxel. Post-discontinuation PSA results were available for all patients and were determined at 2-weekly intervals until starting further anticancer systemic therapy. PSA withdrawal response was defined as a PSA decline by ≥50% from the last on-treatment PSA, with a confirmed decrease ≥3 weeks later. Patient characteristics were evaluated in relation to the AAWS using univariate logistic regression analysis.The median (range) patient age was 70.5 (56-86) years and the median (range) follow-up was 9.0 (0.5-16) months. The most common metastatic sites were the bone (86.7%) and lymph nodes (66.7%). Most patients (70%) had previously received abiraterone and 12 patients (40%) had also received cabazitaxel. The median (range) treatment duration with enzalutamide was 3.68 (1.12-21.39) months. PSA levels after enzalutamide withdrawal were monitored for a median (range) time of 35 (10-120) days. Only one patient (3.3%) had a confirmed PSA response ≥50% after enzalutamide discontinuation. One patient (3.3%) had a confirmed PSA response of between 30 and 50% and another patient (3.3%) had an unconfirmed PSA response of between 30 and 50%. The median overall survival was 15.5 months (95% CI 8.1-24.7). None of the factors analysed in the univariate analysis were significant predictors of PSA decline after enzalutamide discontinuation.This retrospective study provides the first evidence that enzalutamide may have an AAWS in a minority of patients with metastatic castration-resistant prostate cancer. Further studies are needed to confirm the existence of an enzalutamide AAWS and to assess its relevance in prostate cancer management.

OBJECTIVE To compare transdermal oestrogen with oral diethylstilbestrol (DES) as a second- or third-line hormonal therapy in the treatment of prostate cancer. PATIENTS AND METHODS In all, 32 assessable patients who, having already had a relapse on at least one line of hormonal therapy, received transdermal oestrogen therapy as an alternative to oral DES, when DES became unavailable. RESULTS Whereas DES had controlled the prostate-specific antigen (PSA) level for a median of 29 weeks in a group of 15 patients in remission, all but one had an increase in PSA level (median 86% increase above the starting PSA level) within a median of 8 weeks after introducing transdermal therapy. This increase was reversed in seven of the 12 patients who recommenced DES therapy. CONCLUSION Although the use of transdermal oestrogen is currently attracting enthusiasm as a first-line treatment for prostate cancer, these results show that for second- or third-line therapy further cautious research with careful monitoring is necessary.

Ian Butler and Heather Payne present findings from a local study of the form and practice of statutory medical examinations for children looked after by the local authority. They report that only a quarter of children attend such medical examinations and that the quality of these medical contacts is questionable. The paper discusses these findings in the context of what is known generally about the health of children in public care and makes suggestions for developing practice, including the establishment of a designated doctor for substitute child care.

As recently as 2004, treatment options for men with metastatic castration-resistant prostate cancer (mCRPC) were limited, with docetaxel the only approved agent conferring a survival benefit. The therapeutic landscape is now very different, with several agents demonstrating prolonged survival since 2010. New agents for the treatment of mCRPC include sipuleucel-T, cabazitaxel, abiraterone acetate, enzalutamide and radium-223. All are now approved for use in this patient group, although the specific licensing terms vary between agents. In addition, denosumab may have utility in patients with bone metastases. A number of novel agents are also in development with promising initial results. However, because these treatment options have proliferated rapidly, there is currently a paucity of clinical evidence regarding their optimal sequencing. Selection of an appropriate treatment option should take into consideration disease characteristics, drug availability and patient choice. In summary, we discuss several new treatment options available for mCRPC and their integration into the current treatment paradigm.

* The Clinical Effectiveness Unit, The Royal College of Surgeons of England, London, UK yDepartment of Urology, University College Hospital London and St Bartholomew’s Hospital London and Centre for Experimental Cancer Medicine, Bart’s Cancer Unit, London, UK zDepartment of Oncology, University College Hospital, London, UK xDepartment of Oncology, University of Cambridge, Cambridge, UK { Eastern Cancer Registration and Information Service (ECRIC), UK

• To review the published data on predisposing risk factors for cancer treatment-induced haemorrhagic cystitis (HC) and the evidence for the different preventive and therapeutic measures that have been used in order to help clinicians optimally define and manage this potentially serious condition. • Despite recognition that HC can be a significant complication of cancer treatment, there is currently a lack of UK-led guidelines available on how it should optimally be defined and managed. • A systematic literature review was undertaken to evaluate the evidence for preventative measures and treatment options in the management of cancer treatment-induced HC. • There is a wide range of reported incidence due to several factors including variability in study design and quality, the type of causal agent, the grading of bleeding, and discrepancies in definition criteria. • The most frequently reported causal factors are radiotherapy to the pelvic area, where HC has been reported in up to 20% of patients, and treatment with cyclophosphamide and bacillus Calmette-Guérin, where the incidence has been reported as up to 30%. • Mesna (2-mercaptoethane sodium sulphonate), hyperhydration and bladder irrigation have been the most frequently used prophylactic measures to prevent treatment-related cystitis, but are not always effective. • Cranberry juice is widely cited as a preventative measure and sodium pentosanpolysulphate as a treatment, although the evidence for both is very limited. • The best evidence exists for intravesical hyaluronic acid as an effective preventative and active treatment, and for hyperbaric oxygen as an equally effective treatment option. • The lack of robust data and variability in treatment strategies used highlights the need for further research, as well as best practice guidance and consensus on the management of HC.

e16018Background: UK guidelines for treatment of bladder cancer recommend Gemcitabine/Cisplatin (GC) or MVAC (Methotrexate, Vinblastine, Doxorubicin and Cisplatin). Outcomes are similar but reporte...

Purpose: Cabazitaxel (CBZ) improves overall survival in patients withmCRPC previously treated with docetaxel chemotherapy. Prior to cancer drugs fund access of CBZ, patients at University College London Hospital were treated with ECarboF. We report our experiences of CBZ compared with ECarboF. Methods: A retrospective analysis comparing CBZ (10/2013-2/2015) and ECarboF (3/2007-10/2010) was performed. Patients were identified through an electronic prescribing system. Patients’ records were used to identify demographics, treatment responses and toxicities. Survival was estimated using the methods of KaplaneMeier and compared by Cox proportional hazards. Biochemical response rates (BRR; end of treatment PSA > 30% reduction from baseline) and toxicity were compared by chi-squared tests. Results: 23 and 35 patients were identified in the CBZ and ECarboF groups, respectively. CBZ patients were more heavily pre-treated than ECarboF patients (96% versus 0% received second generation hormone therapy). Treatment was generally well tolerated although therewas 1 neutropenic death in each group. Grade 3/4 haematological toxicity was comparable in both groups and grade 3/4 non-haematological toxicities were more frequent in those treated with CBZ. The BRR was similar in the CBZ and ECarboF groups (36% versus 38%, P 1⁄4 0.89). Median progression-free survival (PFS) was 2.7 months (95% CI 2.0e4.9) for CBZ versus 5.3 months (95% CI 2.6e8.0) for ECarboF. Median overall survival (OS) was 9.3 months (95% CI 6.1e17.6) for CBZ versus 13.1 months (95% CI 7.6e27.2) for ECarboF. Therewas a significant difference in PFS in the ECarboF group (HR 1⁄4 0.42; 95% CI 1⁄4 0.24e0.75; P 1⁄4 0.004), and a non-significant trend towards better OS (HR 1⁄4 0.58; 95% CI 1⁄4 0.29e1.14; P 1⁄4 0.114). Conclusion: Patients in the CBZ group were more heavily pre-treated than those in the ECarboF group, probably contributing to improved PFS and OS in ECarboF patients. However, both chemotherapy regimens have activity in the post-docetaxel setting.

296 Background: Increased availability of treatment options in CRPC requires improved biomarkers to optimize decision making for therapeutic sequencing. Despite evidence for the value of CTCs in assessing prognosis and response to treatment, their use in clinical practice is not widely implemented. Clinicians rely on PCWG2 criteria based on PSA, clinical and radiological criteria although these are only inconsistently used in clinical practice. We evaluated the trends for clinical decision-making by physicians treating CRPC. Methods: An online questionnaire was distributed to physicians treating PC from the UK, Switzerland and Australia. Questions on clinical practice, familiarity with progression criteria, use of CTCs and clinical-decision making were formulated. Results: 111 participants replied. Most (84.7%) were oncologists treating ≥ 50 patients per year (65.3%). Although only 39.6% usually used PCWG2 in clinical practice, 74.5% considered PSA, bone scans and CT to be useful for monitoring disease. 55.6% considered PSA to be an important biomarker. A minority were able to identify PSA (41.4%) and bone scan (39.4%) progression criteria by PCWG2. On average, more physicians discontinued cabazitaxel (28%) than docetaxel (10.4%) before cycle 4. Similar number of cycles were given to bone only disease compared to RECIST evaluable patients. Clinical progression was most important for switching treatment for most physicians (90.5%), followed by RECIST (71.6%), bone scan (47.7%), CTC (23.2%) and PSA (21.1%). The main challenge associated with the use of CTCs was the access to technology (84.7%). Most respondents (92%) would not stop therapy with rising PSA but falling CTC counts; most (88.8%) would not stop with declining PSA but rising CTCs. Although 50% acknowledged the prognostic value of CTCs, only 33% would use them to guide decision-making. Conclusions: A significant number of physicians discontinue treatment before 12 weeks. Most physicians rely on clinical progression for decision-making. Knowledge of PCWG2 response and progression criteria is generally suboptimal. Greater physician awareness, access to technology and further evidence and will be required for the implementation of CTCs as a routine biomarker in CRPC.

The management of patients who relapse after radical radiotherapy is a challenging problem for the multidisciplinary team. This group of men may have been considered ineligible or chosen not to be treated with an initial surgical approach as a result of high-risk features or significant comorbid conditions. It is important not to miss the opportunity for definitive local salvage therapies at this stage, and eligible patients should undergo careful restaging to determine their suitability for these approaches. For those men not suitable for local treatment, androgen deprivation therapy (ADT) remains an option.Literature review of the evidence relating to the management of hormone therapy for radiorecurrent prostate cancer.Results from retrospective studies have shown that not all men with biochemical relapse will experience distant metastasis or a reduction in survival due to prostate cancer progression. Therefore, the timing of ADT commencement remains controversial. However, it would seem appropriate to offer immediate therapy to men with advanced disease or unfavourable prostate-specific antigen (PSA) kinetics at relapse. Patients with more favourable risk factors and PSA kinetics may be considered for watchful waiting and deferred ADT to avoid or delay the associated toxicities. Patients with non-metastatic disease can be given the option of castration-based therapy or an antiandrogen such as bicalutamide which may have potential advantages in maintenance of sexual function, physical capacity and bone mineral density but at the expense of an increase in gynaecomastia and mastalgia. Recent data suggest the burden of toxicity from ADT may be reduced by the use of intermittent hormone therapy without compromising survival in this group of patients with radiorecurrence.Hormone therapy remains an option for men with radiorecurrent prostate cancer.

Language-impaired individuals with autism perform poorly on tests such as non-word repetition that are sensitive clinical markers of specific language impairment (SLI). This has fuelled the theory that language impairment in autism represents a co-morbid SLI. However, the underlying cause of these deficits may be different in each disorder. In a novel task, we manipulated non-word stimuli in three ways known to influence the repetition accuracy of children with SLI. Participants with SLI were affected differently by these manipulations to children with autism. Children with autism performed similarly to language-matched typical children in terms of levels and patterns of performance, and types of error made, suggesting that the underlying cognitive cause of non-word repetition deficits is different in each disorder.

What's known on the subject? and What does the study add? Treatment options in the UK for men with metastatic castration-resistant prostate cancer (mCRPC) have been limited, and there is no standard approach, particularly in the second-line setting. The absence of a standard approach is further confounded by the differing definitions and terminologies still used in clinical practice to describe this group of patients (e.g. androgen-independent prostate cancer, hormone refractory prostate cancer, CRPC). With multiple new treatment options emerging, it will be critical to identify key considerations in our decision-making process and to establish an optimum, standardized approach to treatment so that new therapies can be assimilated into an mCRPC treatment algorithm and our routine clinical practice. Most UK oncologists consider patients with advanced, symptomatic prostate cancer as eligible for chemotherapy, although a poor performance status, significant co-morbid factors, advancing age, and the presence of asymptomatic disease with slowly rising prostate-specific antigen levels would prevent chemotherapy use. The decision to retreat with chemotherapy is largely driven by prior response to first-line chemotherapy. Many UK oncologists feel that UK clinical practice is likely to change over the next 5 years, with abiraterone acetate, MDV3100 and cabazitaxel likely to have the most positive impacts in the treatment of mCRPC.To evaluate the current management of patients with advanced prostate cancer by UK oncologists. To gain insights into the future role of emerging therapies.A semi-structured questionnaire was issued by the British Uro-oncology Group to society members during a closed meeting in September 2010. Emerging therapies evaluated were: abiraterone acetate, aflibercept, bevacizumab, cabazitaxel, custirsen, MDV3100, sipuleucel-T and zibotentan.Eighty of 98 (82%) surveys were completed. Responders had on average 189 new referrals, and treated 126 patients with advanced prostate cancer each year. Chemotherapy was used by 86% of responders for patients with symptomatic metastatic castration-resistant prostate cancer (mCRPC), although poor performance status, advancing age and slowly rising prostate-specific antigen levels would prevent chemotherapy use. The decision to retreat with chemotherapy was largely driven by prior response to first-line chemotherapy, with docetaxel preferred for those responding. Many (78%) felt that UK clinical practice was likely to change over the next 5 years, and that abiraterone acetate, MDV3100 and cabazitaxel would have the most positive impact. Opinions regarding the future use of aflibercept and custirsen were mixed. Few (≤3%) would use zibotentan or bevacizumab in the future based on recent negative phase III study results, or because of cost and complexity for sipuleucel-T.Although emerging therapies for mCRPC mean that the future is bright, guidelines are needed to ensure optimum use and sequencing of treatments. Additional costs and anticipated workload associated with new agents will require careful consideration.

Since the Nobel Prize-winning discovery by Huggins and Hodges in 1941 [1] that reducing circulating testosterone levels by orchidectomy or exogenous estrogens has a beneficial effect on patients wi...

Photodynamic therapy (PDT) is being investigated as a treatment for localized prostate cancer. Photodynamic therapy uses a photosensitizing drug which is activated by a specific wavelength of light, in the presence of oxygen. The activated drug reacts with tissue oxygen to produce reactive oxygen species which are responsible for localized tissue necrosis. One of the determinants of the PDT effect is the penetration of light in the prostate. This study assesses the penetration depth of 763 nm light throughout the prostate. Eight men undergoing multiple hollow needle insertion for high dose rate brachytherapy were recruited. 763 nm light, produced by a diode laser, was delivered to the prostate using cylindrically diffusing optical fibers within the plastic needles. Light was detected at different distances from the source, using an isotropic detector within nearby needles. Penetration depth was calculated using the Boltzmann approximation to the diffusion equation. Delivery detector fiber separation was measured on computed tomography. The mean penetration depth was 0.57 cm, but there was within patient variation of a mean factor of 4.3. Further work is ongoing to assess the effect of such variability in light penetration, on the PDT effect.

This two-part study assessed the safety and tolerability of combined treatment with zibotentan (ZD4054), a specific endothelin A receptor antagonist, plus docetaxel in patients with metastatic castration-resistant prostate cancer.Part A was an open-label, dose-finding phase to determine the safety and toxicity profile of zibotentan in combination with docetaxel. Patients received once-daily oral zibotentan 10 mg (initial cohort) or 15 mg in combination with docetaxel 75 mg/m(2) (administered on day 1 of each 21-day cycle) for up to 10 cycles. Part B was a double-blind phase which evaluated the safety and preliminary activity of zibotentan plus docetaxel. Patients were randomized 2:1 to receive zibotentan (at the highest tolerated dose identified in part A) plus docetaxel or placebo plus docetaxel.Six patients were enrolled in part A (n = 3, zibotentan 10 mg; n = 3, zibotentan 15 mg). No dose-limiting toxicity was observed, thus zibotentan 15 mg in combination with docetaxel was evaluated in part B (n = 20, zibotentan plus docetaxel; n = 11, placebo plus docetaxel). CTCAE grade ≥3, most commonly neutropenia or leucopenia, were reported in 10 (50%) and nine (82%) patients in the zibotentan and placebo groups, respectively. One (17%) patient receiving placebo achieved complete response, two (22%) patients receiving zibotentan achieved partial response and stable disease occurred in six (67%) and three (50%) patients receiving zibotentan and placebo, respectively.The tolerability of zibotentan plus docetaxel was consistent with the known profiles of each drug. Sufficient preliminary activity was seen with this combination to merit continued development.

In the UK, cancer care is managed via multidisciplinary teams (MDT). Core members of these teams are typically surgeons, oncologists, radiologists, pathologists and clinical nurse specialists (with other health care professionals potentially present). Good teamwork, including team communication and leadership, has been shown to be a prerequisite for safe care delivery in other health care contexts, but cancer MDT team working processes are yet to be fully explored. This study aimed to assess the self-perceived contribution of oncologists to MDTs, with emphasis on their potential role as team leaders.Data were collected at the British Uro-oncology Group 6th Annual Meeting (Sep 11-12 2009, York, UK). Respondents completed various items related to their perceived contribution to MDTs, aspects of current and potential MDT leadership, team decision making in these meetings, and also demographic information.Seventy-seven oncologists attended the meeting, of whom 61 fully completed the survey (response rate 79%). Oncologists reported that their contribution to the MDT discussion carries equal weight to those of surgeons, radiologists and pathologists. Whereas 83% of respondents reported that MDT chairmanship could rotate, only 39% reported that it does in their own MDTs. More than 90% of respondents thought that oncologists (clinical or medical) could chair these meetings, but only 25% of them had ever chaired their own MDT.Despite a high level of contribution to MDTs and the respect of their colleagues, oncologists are not taking leadership roles within MDTs at the level that they expect. This study raises the question of whether a re-evaluation the leadership of MDTs is required with clinicians from a variety of specialities being given opportunities to develop skills necessary to lead cancer MDTs and improve team performance and ultimately cancer care.

To assess the role of multiparametric magnetic resonance imaging (mp-MRI) of the prostate in evaluating local recurrence of prostate cancer, using transperineal template-guided 5 mm-spaced biopsies as a reference standard, in men treated with external beam radiotherapy (EBRT) for prostate cancer.The study included 13 patients with evidence of biochemical recurrence after EBRT who had undergone mp-MRI and prostate mapping. Each MRI scan (consisting of T1/T2 weighting, dynamic contrast enhancement and diffusion weighting) was reported by two expert uro-radiologists. Each prostate was divided into four regions of interest (ROI), generating 52 paired datasets for analysis.The mean (range) age of the men was 65.5 (55-70) years, the mean prostate-specific antigen (PSA) level before EBRT was 36.6 (4.5-150) ng/mL, the mean time from EBRT to biochemical recurrence was 5.7 (3-10) years and the mean PSA level at the time of recurrence was 7.1 (0.83-27.9) ng/mL. Eleven men had histological evidence of recurrence, with 23 of 52 ROIs involved with cancer. Overall accuracy, as expressed by the area under a receiver-operator curve, was 0.77 and 0.89 for all cancer, with accuracies of 0.86 and 0.93 for those cancers with ≥3 mm biopsy core length. Inter-observer variability was measured by calculating κ coefficients, which showed fair and moderate agreement between radiologists.Interpretation of mpMRI of the prostate after previous EBRT is challenging. Our results show that the accuracy is good using an accurate reference standard. These results need verification in more patients, but have implications for determining presence or absence of local recurrence and subsequent local salvage therapy.

Zibotentan (ZD4054) is a specific endothelin A receptor antagonist in clinical development for the treatment of hormone-resistant prostate cancer (HRPC). In a Phase II trial in patients with pain-free or mildly symptomatic metastatic HRPC, zibotentan was well tolerated with a promising signal for prolonged overall survival compared with placebo. As part of this trial, the impact of zibotentan compared with placebo on health-related quality of life (HRQoL) was assessed.Patients were randomized to receive once-daily oral zibotentan 10 or 15 mg, or matching placebo. Patients were allocated to one of two questionnaires; the Functional Assessment of Cancer Therapy-Prostate (FACT-P) or the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), supplemented by PR25, specific for prostate cancer. Questionnaires were completed at baseline and every 4 weeks until disease progression when study treatment was discontinued.Compliance with questionnaire completion was90% (286 of 312 patients) of the intention-to-treat population at baseline. Of baseline completers who were available for assessment (i.e., had not clinically progressed), 89% (164 of 184) and 83% (73 of 88) completed questionnaires at 12 and 24 weeks, respectively. HRQoL scores from both questionnaires were high at baseline and remained high throughout the study, with scores being similar in the zibotentan and placebo groups. However, some floor and ceiling effects were seen in the EORTC QLQ-C30 questionnaire.High-baseline HRQoL scores were maintained throughout treatment with zibotentan. The FACT-P instrument was selected to further assess the impact of zibotentan on HRQoL in the Phase III clinical trial program.

Prostate specific antigen (PSA) was introduced as a prostate cancer screening tool more than 20 years ago. However, there is continuing debate regarding its utility in screening for prostate cancer. Mass screening is costly, may result in the diagnosis and treatment of prostate cancers that never become clinically significant, and the evidence of a subsequent reduction in mortality is inconclusive. In addition to its role in screening, PSA is also used to monitor the progression of the disease, both localized and metastatic. Although the evidence is contradictory, PSA is still an important tool for monitoring patient progression following treatment of definitive localized prostate cancer. However, its use in monitoring castrate-resistant prostate cancer (CRPC) is more controversial, particularly in the context of novel targeted treatments, which may have little impact on PSA levels. These issues highlight the urgent need to identify prostate cancer biomarkers that will improve early disease detection, increase accuracy of diagnosis, determine the aggressiveness of disease, and monitor treatment efficacy, particularly in late-stage disease. This review discusses the key issues associated with the use of PSA as an early screening tool for prostate cancer, as a prognostic marker to measure disease progression in both early- and late-stage prostate cancer, and as a surrogate endpoint in clinical trials with new agents.

This refereed correspondence responds to claims made in an article published in the Lancet in December 2008 regarding the nature of mandatory reporting laws, and their benefits and disadvantages for child protection.

The management of all stages of prostate cancer is an increasingly complex process and involves a variety of available treatments and many disciplines. Despite prostate-specific antigen (PSA) testing, the presentation of prostate cancer at a locally advanced stage is common in the UK, accounting for one-third of all new cases. There is no universally accepted definition of locally advanced prostate cancer; the term is loosely used to encompass a spectrum of disease profiles that show high-risk features. Men with high-risk prostate cancer generally have a significant risk of disease progression and cancer-related death if left untreated. High-risk patients, including those with locally advanced disease, present two specific challenges. There is a need for local control as well as a need to treat any microscopic metastases likely to be present but undetectable until disease progression. The optimal treatment approach will therefore often necessitate multiple modalities. The exact combinations, timing and intensity of treatment continue to be strongly debated. Management decisions should be made after all treatments have been discussed by a multidisciplinary team (including urologists, oncologists, radiologists, pathologists and nurse specialists) and after the balance of benefits and side effects of each therapy modality has been considered by the patient with regard to his own individual circumstances. This article reviews the current therapy options.

Background: Type 2 diabetes (DM) is a common comorbidity in patients with heart failure (HF). Nutritional management is a key strategy in achieving blood glucose control and decreasing the risk of microvascular complications. The ability of patients with HF to nutritionally self-manage multiple comorbidities is unknown. Purpose: To compare nutritional intake of a group of patients with HF and DM with a group without DM. Methods: A total of 174 patients (66 with DM, age 60± 12 yrs, 35% female, 57% NYHA class III/IV) recruited from HF clinics completed detailed 4-day food diaries that were reviewed by a registered dietitian. Nutrition Data System software was used to determine carbohydrate (total and subtype), protein, fat, cholesterol, and sodium intake. Fasting blood glucose was obtained on a subset of 123 patients. Between-group comparisons were made using independent sample t-tests. Results: Patients with DM consumed a lower percentage of calories from carbohydrate (44% vs. 49%, p=.003) and a greater percentage of calories from protein (19% vs. 16%, p120mg/dl and 40% had a fasting levels > 140mg/dl. Conclusions: Patients with HF and DM primarily limited dietary sugar intake, with only moderate success. Nutritional management of HF has focused on the single nutrient sodium with limited success; these data suggest that teaching for DM may be similarly focused on the single nutrient sugar. This indicates that new, more comprehensive, approaches are needed to help patients meet the challenge of nutritionally managing multiple comorbidities. This research has received full or partial funding support from the American Heart Association, AHA Great Rivers Affiliate (Delaware, Kentucky, Ohio, Pennsylvania & West Virginia).