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Summary Rare cases of vaccine-induced Immune thrombocytopenia and thrombosis (VITT) are being identified after vaccination with the SARS-CoV-2 Oxford–AstraZeneca vaccination. We report on two such patients with associated adrenal involvement, which is now being recognised. Both patients presented with abdominal pain, back pain and vomiting. Case 1 was a 46-year-old male who had received the first dose of the Oxford–AstraZeneca vaccination 8 days earlier. Imaging demonstrated a number of serious thrombotic complications including evolving bilateral adrenal haemorrhage (right adrenal haemorrhage identified at presentation, with the left-sided changes only evident on day 4 of the admission). Case 2 was a 38-year-old female who had received the first dose of Oxford–AstraZeneca vaccination 11 days prior. Imaging demonstrated left renal vein thrombosis and left adrenal infarction. VITT was diagnosed in both cases given these changes and other consistent haematological findings. Both patients were treated empirically for adrenal insufficiency, a diagnosis subsequently confirmed in case 1. We report these two cases of VITT presenting with adrenal complications (haemorrhage and infarction) after Oxford–AstraZeneca vaccination to highlight the association and the need for prompt management of co-existing adrenal insufficiency, especially given the potential for evolving adrenal involvement. Learning points Adrenal complications (thrombosis/infarction/haemorrhage) may develop as a part of vaccine-induced immune thrombocytopenia (VITT) after SARS-CoV-2 Oxford–AstraZeneca vaccination. Evolving adrenal involvement is possible and ongoing assessment is required to identify this promptly. Cortisol levels may be difficult to interpret when assessing for adrenal insufficiency, given high doses of corticosteroids may be used to manage VITT. Clinicians should have a low threshold for starting empirical replacement with corticosteroids until reliable assessment of adrenal function can be performed.

Ward accreditation is fundamental in contemporary healthcare delivery. One NHS trust in southwest England that had been placed in special measures introduced a ward accreditation programme - known as the ASPIRE programme - but the trust's senior nursing leadership team raised concerns about the level of quality assurance provided. Therefore, the trust revised its newly created ward accreditation programme, referring to the evidence base to re-evaluate the metrics used for assessment. Five new elements, including direct registered nurse care time and ward climate, were introduced in the accreditation process. The revision improved confidence in the quality assurance provided by the programme, which became central to the trust's overall improvement plans.

Multiparametric MRI has a changing role in prostate cancer diagnosis. Internationally recognized consensus documents such as prostate imaging reporting and data system version have been developed and adapted to standardize the acquisition and reporting of prostate MRI. The improvement in scanning techniques and development of highly sensitive functional sequences have improved the detection of clinically significant prostate cancer as well as treatment planning and follow up. This has led to a recent NICE recommendation to use prostate MRI as the initial investigation in men with clinically suspected localized disease. The results of several recent international MRI prostate trials are influencing the way imaging is used to stratify which patients require a prostate biopsy as well as how MRI guidance is used to target biopsies.

Funder: North East London Cancer Alliance, Funder: KCL/UCL Comprehensive Cancer Imaging Centre, Funder: UCLH Biomedical Research Centre, Objectives: National guidelines recommend prostate multiparametric (mp) MRI in men with suspected prostate cancer before biopsy. In this study, we explore prostate mpMRI protocols across 14 London hospitals and determine whether standardisation improves diagnostic quality. Methods: An MRI physicist facilitated mpMRI set-up across several regional hospitals, working together with experienced uroradiologists who judged diagnostic quality. Radiologists from the 14 hospitals participated in the assessment and optimisation of prostate mpMRI image quality, assessed according to both PiRADSv2 recommendations and on the ability to “rule in” and/or “rule out” prostate cancer. Image quality and sequence parameters of representative mpMRI scans were evaluated across 23 MR scanners. Optimisation visits were performed to improve image quality, and 2 radiologists scored the image quality pre- and post-optimisation. Results: 20/23 mpMRI protocols, consisting of 111 sequences, were optimised by modifying their sequence parameters. Pre-optimisation, only 15% of T2W images were non-diagnostic, whereas 40% of ADC maps, 50% of high b-value DWI and 41% of DCE-MRI were considered non-diagnostic. Post-optimisation, the scores were increased with 80% of ADC maps, 74% of high b-value DWI and 88% of DCE-MRI to be partially or fully diagnostic. T2W sequences were not optimised, due to their higher baseline quality scores. Conclusions: Targeted intervention at a regional level can improve the diagnostic quality of prostate mpMRI protocols, with implications for improving prostate cancer detection rates and targeted biopsies.

Background Two million non-emergency surgeries are being cancelled globally every week due to the COVID-19 pandemic, which will have a major impact on patients and healthcare systems. Methods During the peak of the pandemic in the United Kingdom, we set up a multicentre cancer network amongst 14 National Health Service institutions, performing urological, thoracic, gynaecological and general surgical urgent and cancer operations at a central COVID-19 cold site. This is a cohort study of 500 consecutive patients undergoing surgery in this network. The primary outcome was 30-day mortality from COVID-19. Secondary outcomes included all-cause mortality and post-operative complications at 30-days. Results 500 patients underwent surgery with median age 62.5 (IQR 51–71). 65% were male, 60% had a known diagnosis of cancer and 61% of surgeries were considered complex or major. No patient died from COVID-19 at 30-days. 30-day all-cause mortality was 3/500 (1%). 10 (2%) patients were diagnosed with COVID-19, 4 (1%) with confirmed laboratory diagnosis and 6 (1%) with probable COVID-19. 33/500 (7%) of patients developed Clavien-Dindo grade 3 or higher complications, with 1/33 (3%) occurring in a patient with COVID-19. Conclusion It is safe to continue cancer and urgent surgery during the COVID-19 pandemic with appropriate service reconfiguration., Highlights • Priority surgeries are being cancelled every week due to the COVID-19 pandemic. • A multicentre surgical referral network was set up as part of an NHS England approach to continuing safe surgery • The referral network consisted of 14 NHS trusts and surgery was performed at a single COVID-19 ‘cold site’. • After 500 surgeries performed, there was a 0% 30-day mortality from COVID-19. • It is safe to continue cancer and priority surgery during the COVID-19 pandemic with appropriate service reconfiguration.

Background High-intensity focused ultrasound (HIFU) is a minimally-invasive treatment for nonmetastatic prostate cancer. Objective To report medium-term outcomes in men receiving primary whole-gland HIFU from a national multi-centre registry cohort. Design, setting, and participants Five-hundred and sixty-nine patients at eight hospitals were entered into an academic registry. Intervention Whole-gland HIFU (Sonablate 500) for primary nonmetastatic prostate cancer. Redo-HIFU was permitted as part of the intervention. Outcome measurements and statistical analysis Our primary failure-free survival outcome incorporated no transition to any of the following: (1) local salvage therapy (surgery or radiotherapy), (2) systemic therapy, (3) metastases, or (4) prostate cancer-specific mortality. Secondary outcomes included adverse events and genitourinary function. Results and limitations Mean age was 65 yr (47–87 yr). Median prostate-specific antigen was 7.0 ng/ml (interquartile range 4.4–10.2). National Comprehensive Cancer Network low-, intermediate-, and high-risk disease was 161 (28%), 321 (56%), and 81 (14%), respectively. One hundred and sixty three of 569 (29%) required a total of 185 redo-HIFU procedures. Median follow-up was 46 (interquartile range 23–61) mo. Failure-free survival at 5 yr after first HIFU was 70% (95% confidence interval [CI]: 64–74). This was 87% (95% CI: 78–93), 63% (95% CI: 56–70), and 58% (95% CI: 32–77) for National Comprehensive Cancer Network low-, intermediate-, and high-risk groups, respectively. Fifty eight of 754 (7.7%) had one urinary tract infection, 22/574 (2.9%) a recurrent urinary tract infection, 22/754 (3%) epididymo-orchitis, 227/754 (30%) endoscopic interventions, 1/754 (0.13%) recto-urethral fistula, and 1/754 (0.13%) osteitis pubis. Of 206 known to be pad-free pre-HIFU, 183/206 (88%) remained pad free, and of 236 with good baseline erectile function, 91/236 (39%) maintained good function. The main limitation is lack of long-term data. Conclusions Whole-gland HIFU is a repeatable day-case treatment that confers low rates of urinary incontinence. Disease control at a median of just under 5 yr of follow-up demonstrates its potential as a treatment for nonmetastatic prostate cancer. Endoscopic interventions and erectile dysfunction rates are similar to other whole-gland treatments. Patient summary In this report we looked at the 5-yr outcomes following whole-gland high-intensity focused ultrasound treatment for prostate cancer and found that cancer control was acceptable with a low risk of urine leakage. However, risk of erectile dysfunction and further operations was similar to other whole-gland treatments like surgery and radiotherapy.

Objective To report medium-term oncological outcomes in men receiving primary focal treatment with high-intensity focused ultrasonography ( HIFU) for prostate cancer (PCa). Patients and methods Consecutive patients with PCa treated with primary focal HIFU at two centres by six treating clinicians were assessed. Patients were submitted to either focal ablation or hemi-ablation using HIFU (Sonablate 500). The primary objective of the study was to assess medium-term oncological outcomes, defined as overall survival, freedom from biopsy failure, freedom from any further treatment and freedom from radical treatment after focal HIFU. The secondary objective was to evaluate the changes in pathological features among patients treated with focal HIFU over time. We also assessed the relationship between year of surgery and 5-year retreatment probability. Results A total of 1032 men treated between November 2005 and October 2017 were assessed. The median age was 65 years and median prostate-specific antigen level was 7 ng/mL. The majority of patients had a Gleason score of 3 + 4 or above (80.3%). The median (interquartile range) follow-up was 36 (14-64) months. The overall survival rates at 24, 60 and 96 months were 99%, 97% and 97%, respectively. Freedom from biopsy failure, defined as absence of Gleason 3 + 4 disease, was 84%, 64% and 54% at 24, 60 and 96 months. Freedom from any further treatment was 85%, 59% and 46% at 24, 60 and 96 months, respectively. Approximately 70% of patients who were retreated received a second focal treatment. Freedom from radical treatment was 98%, 91% and 81% at 24, 60 and 96 months. During the study period, we observed an increase in the proportion of patients undergoing focal HIFU with Gleason 3 + 4 disease and with T2 stage disease as defined by multiparametric magnetic resonance imaging. Finally, there was a reduction over time in the proportion of patients undergoing re-treatment within 5 years of first treatment. Conclusions Focal HIFU for PCa is a feasible therapeutic strategy, with acceptable survival and oncological results and a reduction in the 5-year retreatment rates over the last decade. Re-do focal treatment is a feasible technique whose functional and oncological outcomes have still to be evaluated.

Background Tissue preservation by means of focal therapy offers some men with clinically significant prostate cancer an alternative to standard care that appears to confer favourable genito-urinary outcomes. The precise estimates of these outcomes have so far been based on small series. Objective This analysis pools the sexual domain related patient reported outcomes from three prospective, registered studies that represent a range of inclusion criteria. Design, setting, and participants One-hundred and eighteen men with localised prostate cancer (prostate specific antigen ≤ 15ng/ml, Gleason ≤ 4+3, stage ≤ T3aN0M0) treated in a tissue-preserving manner using high intensity focused ultrasound from three registered studies were included. Data on International Index of Erectile Function (IIEF-5) scores and use of phosphodiesterase-5-inhibitors were collected at baseline, and 1 mo, 3 mo, 6 mo, 9 mo, and 12 mo postoperatively. The IIEF-15 total and individual domain scores were used to assess overall sexual function. Urinary function was assessed with the International Prostate Symptom Score (IPSS), IPSS quality-of-life, and UCLA-Expanded Prostate Cancer Index Composite continence questionnaires. General health status was derived by means of the Charlson score. Multiple linear regression was used to assess whether age, grade, stage, qualitative scores (IIEF, IPSS, Expanded Prostate Cancer Index Composite, Charlson), or focal therapy type duration were associated with IIEF-5 and IIEF-15 scores at 12 mo. Results and limitations Median age was 63 yr (interquartile range [IQR] 52–70 yr). Median IIEF-erectile score at baseline was 23 (IQR 11–28). This declined significantly to 9 (IQR 3–22, p p =0.30) at 1 yr posttreatment. Changes in total IIEF and other IIEF domains were only significantly different from preoperative values at 1 mo and 3 mo postoperatively. In the same period, the proportion of men using phosphodiesterase-5-inhibitors was 10% preoperatively, reaching 43% and 42% at 6 mo and 9 months before declining to 37% at 1 yr. The only baseline determinants of postoperative erectile function were total IIEF and IIEF-erectile function scores ( p =0.002). The primary limitation of our study is the relatively short follow-up of 1 yr. Conclusion Men who received a range of tissue preserving therapies from the three pertinent studies experienced small decreases in total IIEF, erectile, and individual sexual domain scores that are not significantly different to those recorded at baseline. The only determinant of erectile dysfunction after tissue preserving therapy was preoperative erectile dysfunction status. Tissue preservation confers a high probability of maintaining erectile function that appears independent of all perioperative factors with the exception of baseline status. Patient summary In this report, the largest prospectively collected and published set of patients with erectile dysfunction outcomes post–focal therapy for prostate cancer, we have found a return to baseline International Index of Erectile Function–erectile and total International Index of Erectile Function scores by 6 mo post–focal therapy which was maintained at 1 yr, with the majority of patients not on any form of medical treatment for their erectile dysfunction at that point. Focal therapy may represent a suitable alternative for men of any age or comorbidity wishing to maintain erectile function.

Minimally-invasive therapies in localized prostate cancer offer the potential to reduce side effects and the healthcare burden/costs associated with radical modalities such as surgery or radiotherapy. As radical treatments carry significant perioperative morbidity (wound infection, haemorrhage, hospital stay), potentially life-long side effects (such as incontinence, erectile dysfunction, rectal toxicity), and fail to cure many men, ablative therapies that reduce treatment burden while retaining acceptable cancer control have increasingly become areas of evaluation. This chapter reviews the role of these approaches and the therapeutic dilemma that men with localized low volume prostate cancer currently face as in the context of novel therapies which aim to find a middle ground—tissue-preserving focal therapy—that follows the paradigm of almost all other solid organ cancers.

BACKGROUND: To evaluate the safety and clinical feasibility of focal irreversible electroporation (IRE) of the prostate. METHODS: We assessed the toxicity profile and functional outcomes of consecutive patients undergoing focal IRE for localised prostate cancer in two centres. Eligibility was assessed by multi-parametric magnetic resonance imaging (mpMRI) and targeted and/or template biopsy. IRE was delivered under transrectal ultrasound guidance with two to six electrodes positioned transperineally within the cancer lesion. Complications were recorded and scored accordingly to the NCI Common Terminology Criteria for Adverse Events; the functional outcome was physician reported in all patients with at least 6 months follow-up. A contrast-enhanced MRI 1 week after the procedure was carried out to assess treatment effect with a further mpMRI at 6 months to rule out evidence of residual visible cancer. RESULTS: Overall, 34 patients with a mean age of 65 years (s.d.=±6) and a median PSA of 6.1 ng ml(-1) (interquartile range (IQR)= 4.3-7.7) were included. Nine (26%), 24 (71%) and 1 (3%) men had low, intermediate and high risk disease, respectively (D'Amico criteria). After a median follow-up of 6 months (range 1-24), 12 grade 1 and 10 grade 2 complications occurred. No patient had grade >/= 3 complication. From a functional point of view, 100% (24/24) patients were continent and potency was preserved in 95% (19/20) men potent before treatment. The volume of ablation was a median 12 ml (IQR=5.6-14.5 ml) with the median PSA after 6 months of 3.4 ng ml(-1) (IQR=1.9-4.8 ng ml(-1)). MpMRI showed suspicious residual disease in six patients, of whom four (17%) underwent another form of local treatment. CONCLUSIONS: Focal IRE has a low toxicity profile with encouraging genito-urinary functional outcomes. Further prospective development studies are needed to confirm the functional outcomes and to explore the oncological potential.

Context The great controversy surrounding the treatment of localized prostate cancer is related with its possibilities of radical treatment or active surveillance. The objective of this paper is to analyze the rationale selection among current focal therapy modalities regarding tumor and patient selection. Evidence acquisition Current articles about advantages and disadvantages on the treatment of localized prostate cancer as well as information about focal therapy regarding tumor selection, characteristics and indications cited in MEDLINE search were reviewed. Summary of evidence Focal therapy standardized criteria must be: low risk tumors, PSA 15. Conclusions Focal therapy is an alternative for localized prostate cancer treatment. However, some aspects of their diagnosis and selection criteria should be defined by prospective studies which should provide knowledge about the indication for focal therapy.

Resumen Contexto Los tratamientos radicales o de seguimiento activo son alternativas en el manejo del cancer de prostata localizado, ambos no exentos de riesgos y efectos secundarios. El objetivo de este trabajo es analizar las diferentes posibilidades de la terapia focal en sus diferentes opciones para tratar el cancer de prostata localizado. Adquisicion de evidencia Realizamos una revision en Medline de las diferentes posibilidades de tratamiento focal desde el punto de vista tecnico, desarrolladas en la actualidad con atencion a los estudios prospectivos aleatorizados, asi como las formas de seguimiento y evolucion de resultados. Sintesis de evidencia Diferentes tecnicas en este momento estan disponibles para realizar terapia focal, basicamente aquellas minimamente invasivas —terapia vascular fotodinamica (TVF), crioterapia, braquiterapia, ultrasonido focalizado de alta intensidad (HIFU), laser intersticial— que permiten acceso directo y dirigido a la glandula. Los resultados preliminares de los estudios actuales demuestran una buena aceptabilidad de las tecnicas con escasos efectos secundarios y buenos resultados oncologicos. La biopsia junto con la resonancia magnetica nuclear (RMN) son las guias de seguimiento en estos pacientes, siendo el papel del antigeno prostatico especifico (PSA) menos definido. Conclusiones La terapia focal es en la actualidad una alternativa con tecnicas disponibles para una buena ejecucion. Los datos actuales apuntan a una escasa morbilidad y buenos resultados oncologicos que hacen de la terapia focal una posible alternativa de tratamiento en los tumores localizados, a la espera de los resultados de mas estudios aleatorizados.

Resumen Contexto El tratamiento del cancer de prostata localizado esta sujeto a gran controversia en lo referente a sus posibilidades de tratamiento, radical o seguimiento activo. El objetivo de este trabajo es analizar la racionalidad de la terapia focal, seleccion de tumores y pacientes en el entorno de las alternativas existentes. Adquisicion de evidencia Revisamos la literatura actual en Medline, relacionada con las ventajas e inconvenientes sobre el tratamiento de cancer de prostata localizado, asi como la informacion publicada sobre la terapia focal en referencia a la seleccion de tumores, caracteristicas e indicaciones para terapia focal. Sintesis de evidencia Los tumores de bajo riesgo, PSA 15. Conclusiones La terapia focal puede ser una alternativa para tratar el cancer de prostata localizado, si bien algunos de sus aspectos diagnosticos y de seleccion deberan ser definidos por estudios prospectivos, que esperamos nos puedan aportar conocimiento sobre la indicacion de la terapia focal.

Context The great controversy surrounding the treatment of localized prostate cancer is related with its possibilities of radical treatment or active surveillance. The objective of this paper is to analyze the rationale selection among current focal therapy modalities regarding tumor and patient selection. Evidence acquisition Current articles about advantages and disadvantages on the treatment of localized prostate cancer as well as information about focal therapy regarding tumor selection, characteristics and indications cited in MEDLINE search were reviewed. Summary of evidence Focal therapy standardized criteria must be: low risk tumors, PSA 15. Conclusions Focal therapy is an alternative for localized prostate cancer treatment. However, some aspects of their diagnosis and selection criteria should be defined by prospective studies which should provide knowledge about the indication for focal therapy.

High intensity focused ultrasound may have a role as an alternative to standard radical therapies for localized prostate cancer. An attribute of high intensity focused ultrasound is that it can be repeated. We determined morbidity after primary and redo high intensity focused ultrasound.We performed an academic lead analysis of United Kingdom registry data on high intensity focused ultrasound treatments at 3 centers using patient reported continence and sexual function outcomes. Validated questionnaires were completed before and after each ultrasound treatment.A total of 359 patients received 1 whole gland high intensity focused ultrasound treatment for localized prostate cancer from October 2004 to June 2012, of whom 130 (36.2%) received re-treatment. Median followup was 27 months (range 3 to 81) after re-treatment. When analyzing adverse events, 10.8% of patients experienced urinary tract infection after the first treatment compared to 3.9% after re-treatment (p=0.009). Urethral dilatation was required in 13.8% and 14.0% of patients after first and redo ultrasound treatments (p=0.7), and bladder neck incision was required in 9.2% and 11.6%, respectively (p=0.2). Before and after re-treatment 73.3% and 55.1% of patients had no leak, and 2.7% and 9.0% used daily pads (p0.001 and p=0.07, respectively). Analysis of erectile function showed that 56.2% and 56.0% of patients were potent before and after re-treatment, respectively (p=0.9).Redo high intensity focused ultrasound is associated with an increase in urinary side effects but sexual side effects do not appear to be significantly increased. The number of adverse events seems to be equivalent after first and redo treatments. Meticulous patient selection is of paramount importance when selecting men for redo high intensity focused ultrasound.

INTRODUCTION: Focal therapy may reduce the toxicity of current radical treatments while maintaining the oncological benefit. Irreversible electroporation (IRE) has been proposed to be tissue selective and so might have favourable characteristics compared to the currently used prostate ablative technologies. The aim of this trial is to determine the adverse events, genito-urinary side effects and early histological outcomes of focal IRE in men with localised prostate cancer. METHODS: This is a single centre prospective development (stage 2a) study following the IDEAL recommendations for evaluating new surgical procedures. Twenty men who have MRI-visible disease localised in the anterior part of the prostate will be recruited. The sample size permits a precision estimate around key functional outcomes. Inclusion criteria include PSA ≤ 15 ng/ml, Gleason score ≤ 4 + 3, stage T2N0M0 and absence of clinically significant disease outside the treatment area. Treatment delivery will be changed in an adaptive iterative manner so as to allow optimisation of the IRE protocol. After focal IRE, men will be followed during 12 months using validated patient reported outcome measures (IPSS, IIEF-15, UCLA-EPIC, EQ-5D, FACT-P, MAX-PC). Early disease control will be evaluated by mpMRI and targeted transperineal biopsy of the treated area at 6 months. DISCUSSION: The NEAT trial will assess the early functional and disease control outcome of focal IRE using an adaptive design. Our protocol can provide guidance for designing an adaptive trial to assess new surgical technologies in the challenging landscape of health technology assessment in prostate cancer treatment.

Context The current management of localized prostate cancer is a therapeutic challenge with different options including active radicals or active follow-up. The aim of this paper is to analyze the feasibility and validity of the “Focal” active treatment versus the concept of active follow-up or Radical Treatment. Evidence acquisition We reviewed the literature on the various diagnostic methods, advantages, and difficulties of active follow-up and Radical Treatment, versus focal therapy with the possibilities of defining characteristics of aggressiveness and patient selection. Evidence synthesis The mesh biopsy techniques along with multiparametric magnetic resonance imaging and association of factors such as tumor size, length of affected cylinder and Gleason are parameters that allow us to define location and definition of clinically significant tumors and subsidiary of focal therapies. Conclusions The definition, location and aggressiveness of prostate cancer in low-intermediate risk tumors can be defined avoiding radical therapies with their side effects or the risks of underestimating tumors as in active follow-up without the minimum side effects.

Resumen Contexto El manejo actual del cancer de prostata localizado supone un reto terapeutico con diferentes opciones, incluyendo las activas radicales o el seguimiento activo. El objetivo de este trabajo es analizar la posibilidad y validez del tratamiento activo «focal» frente al concepto de seguimiento activo o tratamiento radical. Adquisicion de evidencia Realizamos una revision de la literatura sobre los diferentes metodos diagnosticos, ventajas o dificultades del seguimiento activo y tratamiento radical frente a la terapia focal, con las posibilidades de definicion de caracteristicas de agresividad y seleccion de pacientes. Sintesis de evidencia Las tecnicas de biopsia con rejilla junto con la resonancia nuclear magnetica nuclear multiparametrica y la asociacion de factores como el tamano del tumor, la longitud del cilindro afecto y Gleason son parametros que nos permiten afinar en la localizacion y definicion de tumores clinicamente significantes y subsidiarios de terapias focales. Conclusiones La definicion, localizacion y agresividad del cancer de prostata en tumores de riesgo bajo-intermedio puede ser definida evitando las terapias radicales con sus efectos secundarios, o los riesgos de subestimar tumores como en el seguimiento activo con los minimos efectos secundarios.

To evaluate the feasibility of using computer-assisted, deformable image registration software to enable three-dimensional (3D), multi-parametric (mp) magnetic resonance imaging (MRI)-derived information on tumour location and extent, to inform the planning and conduct of focal high-intensity focused ultrasound (HIFU) therapy.

Purpose Irreversible electroporation has attractive attributes for focal ablation, namely nonthermal effect, precise demarcation of treatment and tissue selectivity. We report a prospective development study investigating focal irreversible electroporation. Materials and Methods A total of 20 men with certain characteristics were recruited for study, including a visible index lesion on anterior magnetic resonance imaging that was concordant with transperineal targeted and template prostate mapping biopsy, absent clinically significant disease noted elsewhere (University College London definition 2) and prostate specific antigen 15 ng/ml or less. Our primary objective was to determine the side effect profile at 12 months. Secondary objectives included the domain specific toxicity profile using patient reported outcomes and early disease control using magnetic resonance imaging targeted biopsy. Results A total of 19 patients with median age of 60 years (IQR 53–66) and median prostate specific antigen 7.75 ng/ml (IQR 5.5–10.03) were treated. Of the patients 16 were available for estimating the first outcome as 1 was lost to followup and 2 had received another form of treatment by study end. All 16 men had pad-free/leak-free continence at 12 months. The proportion of men with erection sufficient for penetration decreased from 12 of 16 (75%) to 11 of 16 (69%). No serious adverse events were recorded. There was a statistically significant improvement in urinary symptoms according to changes in UCLA-EPIC (UCLA Expanded Prostate Cancer Index Composite) and I-PSS (International Prostate Symptom Score) (p = 0.039 and 0.001, respectively). Erectile function remained stable according to the change in IIEF-15 (15-Item International Index of Erectile Function) (p = 0.572). Median prostate specific antigen significantly decreased to 1.71 ng/ml (p = 0.001). One man refused followup biopsy. No residual disease was found in 11 patients (61.1%). One man (5.6%) harbored clinically insignificant disease and the remaining 6 (33.3%) harbored clinically significant disease. Conclusions Focal irreversible electroporation has low genitourinary toxicity. Additional studies are needed to optimize patient selection and treatment parameters.

effects of combined “TURP+HIFU” for local radical ablation of high risk Prostate Cancer (hrPCa). METHODS: 480 hrPCa patients (T3-4 or initial PSA >20 or Gleason 8-10, N0, M0) were treated with TURP and consecutive transrectal complete HIFU Ablation with Ablatherm Integrated Imaging (EDAP-TMS, Lyon-France) and followed prospectively up to 17 years. “Disease progression” (failure) was defined as: Last PSA>initial PSA (PSAi) or M +/or onset of Salvage Therapy. RESULTS: In a high risk PCa patient cohort with a median follow up of 7 years (0.6-17.8) over all survival was 71.7%, metastasis free survival 91%, cancer specific survival 92.9% and progression free survival 63%. 30% needed adjuvant salvage ADT and 7% other salvage therapies in follow up after median 1.5 (0.1-12.5) years. Therapy induced side effects were: Stress Incontinence 7.9%, Obstruction: 3.7%, Fistula/Osteitis os pubis: 1.5%; UTI: 21.4%. CONCLUSIONS: Local radical prostate cancer ablation through transurethral resection (TURP) and transrectal complete High Intensity Focused Ultrasound (HIFU) with Ablatherm integrated imaging is a valid therapy even in high risk prostate cancer patients.

What's known on the subject? and What does the study add? Whole gland brachytherapy has been used to successfully treat prostate cancer but the protocol for focal therapy has not previously been established. The consensus findings provide guidance on patient selection for focal brachytherapy as well as recommendations for conducting therapy and patient follow-up. Low dose rate prostate brachytherapy is an effective treatment for localized prostate cancer. Recently, it has been considered for use in a focused manner whereby treatment is targeted only to areas of prostate cancer. The objective of focal brachytherapy is to provide effective cancer control for low-risk disease but with reduced genitourinary and rectal side-effects in a cost-effective way. We report on the outputs of a consensus meeting of international experts in brachytherapy and focal therapy convened to consider the feasibility and potential development of focal brachytherapy. A number of factors were considered for focal brachytherapy including optimal patient selection, disease characterization and localization, treatment protocols and outcome measures. The consensus meeting also addressed the design of a clinical trial that would assess the oncological outcomes and side-effect profiles resulting from focal brachytherapy.

Summary Background Radical whole-gland therapy can lead to significant genitourinary and rectal side-effects for men with localised prostate cancer. We report on whether selective focal ablation of unifocal and multifocal cancer lesions can reduce this treatment burden. Methods Men aged 45–80 years were eligible for this prospective development study if they had low-risk to high-risk localised prostate cancer (prostate specific antigen [PSA] ≤15 ng/mL, Gleason score ≤4 + 3, stage ≤T2), with no previous androgen deprivation or treatment for prostate cancer, and who could safely undergo multiparametric MRI and have a general anaesthetic. Patients received focal therapy using high-intensity focused ultrasound, delivered to all known cancer lesions, with a margin of normal tissue, identified on multiparametric MRI, template prostate-mapping biopsies, or both. Primary endpoints were adverse events (serious and otherwise) and urinary symptoms and erectile function assessed using patient questionnaires. Analyses were done on a per-protocol basis. This study is registered with ClinicalTrials.gov, number NCT00561314. Findings 42 men were recruited between June 27, 2007, and June 30, 2010; one man died from an unrelated cause (pneumonia) 3 months after treatment and was excluded from analyses. After treatment, one man was admitted to hospital for acute urinary retention, and another had stricture interventions requiring hospital admission. Nine men (22%, 95% CI 11–38) had self-resolving, mild to moderate, intermittent dysuria (median duration 5·0 days [IQR 2·5–18·5]). Urinary debris occurred in 14 men (34%, 95% CI 20–51), with a median duration of 14·5 days (IQR 6·0–16·5). Urinary tract infection was noted in seven men (17%, 95% CI 7–32). Median overall International Index of Erectile Function-15 (IIEF-15) scores were similar at baseline and at 12 months (p=0·060), as were median IIEF-15 scores for intercourse satisfaction (p=0·454), sexual desire (p=0·644), and overall satisfaction (p=0·257). Significant deteriorations between baseline and 12 months were noted for IIEF-15 erectile (p=0·042) and orgasmic function (p=0·003). Of 35 men with good baseline function, 31 (89%, 95% CI 73–97) had erections sufficient for penetration 12 months after focal therapy. Median UCLA Expanded Prostate Cancer Index Composite (EPIC) urinary incontinence scores were similar at baseline as and 12 months (p=0·045). There was an improvement in lower urinary tract symptoms, assessed by International Prostate Symptom Score (IPSS), between baseline and 12 months (p=0·026), but the IPSS-quality of life score showed no difference between baseline and 12 months (p=0·655). All 38 men with no baseline urinary incontinence were leak-free and pad-free by 9 months. All 40 men pad-free at baseline were pad-free by 3 months and maintained pad-free continence at 12 months. No significant difference was reported in median Trial Outcomes Index scores between baseline and 12 months (p=0·113) but significant improvement was shown in median Functional Assessment of Cancer Therapy (FACT)-Prostate (p=0·045) and median FACT-General scores (p=0·041). No histological evidence of cancer was identified in 30 of 39 men biopsied at 6 months (77%, 95% CI 61–89); 36 (92%, 79–98) were free of clinically significant cancer. After retreatment in four men, 39 of 41 (95%, 95% CI 83–99) had no evidence of disease on multiparametric MRI at 12 months. Interpretation Focal therapy of individual prostate cancer lesions, whether multifocal or unifocal, leads to a low rate of genitourinary side-effects and an encouraging rate of early absence of clinically significant prostate cancer. Funding Medical Research Council (UK), Pelican Cancer Foundation, and St Peters Trust.

Item does not contain fulltext BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) may have a role in detecting clinically significant prostate cancer in men with raised serum prostate-specific antigen levels. Variations in technique and the interpretation of images have contributed to inconsistency in its reported performance characteristics. OBJECTIVE: Our aim was to make recommendations on a standardised method for the conduct, interpretation, and reporting of prostate mpMRI for prostate cancer detection and localisation. DESIGN, SETTING, AND PARTICIPANTS: A consensus meeting of 16 European prostate cancer experts was held that followed the UCLA-RAND Appropriateness Method and facilitated by an independent chair. MEASUREMENT: Before the meeting, 520 items were scored for "appropriateness" by panel members, discussed face to face, and rescored. RESULTS AND LIMITATIONS: Agreement was reached in 67% of 260 items related to imaging sequence parameters. T2-weighted, dynamic contrast-enhanced, and diffusion-weighted MRI were the key sequences incorporated into the minimum requirements. Consensus was also reached on 54% of 260 items related to image interpretation and reporting, including features of malignancy on individual sequences. A 5-point scale was agreed on for communicating the probability of malignancy, with a minimum of 16 prostatic regions of interest, to include a pictorial representation of suspicious foci. Limitations relate to consensus methodology. Dominant personalities are known to affect the opinions of the group and were countered by a neutral chairperson. CONCLUSIONS: Consensus was reached on a number of areas related to the conduct, interpretation, and reporting of mpMRI for the detection, localisation, and characterisation of prostate cancer. Before optimal dissemination of this technology, these outcomes will require formal validation in prospective trials.

Objective: The launch of Choose and Book has enabled patients to choose from at least four providers of healthcare to reduce long waiting times for elective surgery. We aimed to investigate what factors patients consider when deciding on their choice of hospital and to establish what weight patients placed on each of these factors when making their choice. Patients and methods: Patients attending general urology outpatient clinics during a 3-month period were invited to complete a questionnaire grading these factors in level of importance to them. Results: Hospital cleanliness was the most important factor when choosing a hospital, followed by hospital reputation. Conclusions: Cleanliness and hygiene standards within a hospital are increasingly important to patients with the rise in hospital acquired infections, heightened by a high level of media interest in hospital hygiene. The behaviour of patients in choosing where and when and by whom they want their health care will clearly have an impact on waiting times, although the true impact of this is as yet difficult to establish. With respect to urology, this may affect the choice of hospital as well as the treating urology consultant. For patients to make these choices they will need more information about their options and General Practitioners will need to provide appropriate guidance.

Purpose Focal brachytherapy targeted to an individual lesion(s) within the prostate may reduce side effects experienced with whole-gland brachytherapy. The outcomes of a consensus meeting on focal prostate brachytherapy were used to investigate optimal dosimetry of focal low-dose-rate (LDR) prostate brachytherapy targeted using multiparametric magnetic resonance imaging (mp-MRI) and transperineal template prostate mapping (TPM) biopsy, including the effects of random and systematic seed displacements and interseed attenuation (ISA). Methods and Materials Nine patients were selected according to clinical characteristics and concordance of TPM and mp-MRI. Retrospectively, 3 treatment plans were analyzed for each case: whole-gland (WG), hemi-gland (hemi), and ultra-focal (UF) plans, with 145-Gy prescription dose and identical dose constraints for each plan. Plan robustness to seed displacement and ISA were assessed using Monte Carlo simulations. Results WG plans used a mean 28 needles and 81 seeds, hemi plans used 17 needles and 56 seeds, and UF plans used 12 needles and 25 seeds. Mean D90 (minimum dose received by 90% of the target) and V100 (percentage of the target that receives 100% dose) values were 181.3 Gy and 99.8% for the prostate in WG plans, 195.7 Gy and 97.8% for the hemi-prostate in hemi plans, and 218.3 Gy and 99.8% for the focal target in UF plans. Mean urethra D10 was 205.9 Gy, 191.4 Gy, and 92.4 Gy in WG, hemi, and UF plans, respectively. Mean rectum D2 cm 3 was 107.5 Gy, 77.0 Gy, and 42.7 Gy in WG, hemi, and UF plans, respectively. Focal plans were more sensitive to seed displacement errors: random shifts with a standard deviation of 4 mm reduced mean target D90 by 14.0%, 20.5%, and 32.0% for WG, hemi, and UF plans, respectively. ISA has a similar impact on dose-volume histogram parameters for all plan types. Conclusions Treatment planning for focal LDR brachytherapy is feasible. Dose constraints are easily met with a notable reduction to organs at risk. Treating smaller targets makes seed positioning more critical.

Background Although localised prostate cancer is multifocal in most instances, the index lesion might be responsible for disease progression. Objective To determine the early genitourinary functional and cancer control outcomes of index lesion ablation. Design, setting, and participants This was a single-centre prospective development study in which 56 men were treated (July 2009–January 2011). The mean age was 63.9 yr (standard deviation 5.8) and median prostate-specific antigen (PSA) was 7.4 ng/ml (interquartile range [IQR] 5.6–9.5). There were seven (12.5%) low-risk, 47 (83.9%) intermediate-risk, and two (3.6%) high-risk cancers. Intervention Multiparametric magnetic resonance imaging (mpMRI) and prostate biopsies to localise disease, followed by index lesion ablation using high-intensity focused ultrasound. Outcome measurements and statistical analysis Primary outcomes were genitourinary side effects measured using validated questionnaires. Secondary outcomes included absence of clinically significant disease at 12 mo. Results and limitations The composite of leak-free, pad-free continence, and erections sufficient for penetration decreased from a baseline frequency of 40/56 (71.4%) to 33/56 (58.9%) at 12 mo. Pad-free and leak-free, pad-free continence was preserved in 48/52 (92.3%) and 46/50 (92.0%) patients, respectively. Erections sufficient for intercourse were preserved in 30/39 (76.9%) patients. The median PSA nadir decreased to 2.4 ng/ml (IQR 1.6–4.1). At 12 mo, 42/52 (80.8%) patients had histological absence of clinically significant cancer and 85.7% (48/56) had no measurable prostate cancer (biopsy and/or mpMRI). Two (3.6%) patients had clinically significant disease in untreated areas not detected at baseline. The main study limitation is the short follow-up duration. Conclusions Index lesion ablation had low rates of genitourinary side effects and acceptable short-term absence of clinically significant cancer. Comparative effectiveness trials are required to assess cancer control outcomes against radical therapy. Patient summary In this study we looked at whether it is possible to treat the largest and highest-grade tumour in men who have more than one known prostate tumour. We show that the side effects of targeted ablation were low, with acceptable rates of early cancer control. Larger studies with longer follow-up are needed. Trial registration NCT00988130

INTRODUCTION: Focal therapy for localized prostate cancer has the potential for oncological control without the side effects of radical therapies. However, there is currently no validated method for monitoring treatment success. We assessed the diagnostic performance of prostate-specific antigen (PSA) parameters and MRI compared to histological outcomes following focal therapy. PATIENTS AND METHODS: Patients from 3 Ethics Review Board approved prospective studies of focal high intensity-focused ultrasound (HIFU) (Sonablate 500) for localized prostate cancer (T1c-T3a, Gleason grade≤4+3, and PSA≤20). Post-HIFU PSA nadir, 6-month PSA, PSA density, and early (3mm or any Gleason 4 tumor. CONCLUSIONS: Early and late MRI performed better than PSA measurements in the detection of residual tumor after focal therapy.

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.

rates to QOL surveys, as well as factors associated with response, in these two patient populations. METHODS: Patients who underwent surgery for RCC or PCa at our institution between 2006 and 2012 were offered enrollment in a prospective registry that included baseline and annual QoL assessment. We identified 201 patients in the RCC registry and 616 patients in the PCa registry who completed a baseline QoL survey and were mailed a follow-up QoL at one and two years post surgery [RCC: SF-36, FACTeG (73 questions), PCa: EPIC, IIEF, Max-PC (80 questions)]. We compared patient characteristics between responders (i.e. those that returned at least a one or two-year follow-up) and non-responders using a Wilcoxon rank-sum test for continuous variables and a Fisher’s Exact test for categorical variables. To compare cancer-specific survival (CSS) between responders and non-responders we employed Cox Proportional Hazards models. All statistical tests were two-sided, with significance set at p1⁄4 0.05. RESULTS: The overall response rate for the PCa and RCC groups were 63% and 48% (p

INTRODUCTION AND OBJECTIVES: Focal therapy has shown encouraging low rates of genitourinary side-effects in the treatment of localised prostate cancer. As biochemical failure is difficult to define discussion has centred on rates of transition to whole-gland local therapy and need for systemic therapy. We report on our registry experience of over 1,000 men treated with transrectal HIFU. METHODS: Our independent academic HIFU registry incorporates a total of 830 patients with low, intermediate and high risk, stage T2a-T3aN0M0 prostate adenocarcinoma treated between 2004 and 2012 in a primary setting. Of these, 509 had focal HIFU treatment (Sonablate 500); 313 had whole-gland treatment. We defined our composite failure as need for whole-gland therapy and/or systemic therapy. RESULTS: Of 509 men undergoing focal HIFU therapy, 84 required redo-HIFU (17%). None of the patients in this group went on to have radical prostatectomy. 1% (5/509) had salvage radiotherapy and

INTRODUCTION AND OBJECTIVES: To compare the oncological results of radial prostatectomy (RP) and High Intensity Focused Ultrasound (HIFU) performed in the same urological department during the same period (2000 – 2005). METHODS: All consecutive patients 70 years old were included in this study. All data were collected prospectively on secured database. Patients treated with HIFU underwent systematic control biopsy and a second HIFU session in case of positive biopsy. RESULTS: A total of 723 patients were included in the study: 423 RP (open: 259, Laparoscopic: 154) and 310 HIFU. Except the mean age (RP: 61 years, HIFU: 64 years, p 0.001) they was no difference between the 2 groups for PSA (RP: 9.2ng/ml, HIFU: 8.5ng/ ml), Gleason score (RP: 6.3 1, HIFU: 6.2 1) and the D’Amico risk group (Low 42.6% vs. 39.5%, intermediate 43.1% vs. 44.8% and high 14.4% vs. 15.7% for RP and HIFU respectively). The mean nadir PSA was significantly different between RP and HIFU: 0.17ng/ml (median: 0.06ng/ml) and 0.72ng/ml (median: 0.16ng/ml). A salvage EBRT was performed in 22.3% of the RP group versus 34.5% in the HIFU group (p 0.01) but the rate of palliative androgen deprivation (AD) was not different: 9.4% for RP and 12.3% for HIFU (p 0.22). At 9 years, no difference was found in the overall survival rate (RP: 93%, HIFU: 89%, p 0.1) and in the cancer specific survival rate (RP: 99%, HIFU: 97%, p 0.31). The metastasis survival rate was 97% for RP and 94% for HIFU (p 0.01). The AD free survival rate was 87% in the RP group and 85% in the HIFU group (p 0.29). CONCLUSIONS: The RP provide a better local control and metastasis free survival rate at 9 years compared to HIFU. However, the specific survival rate and AD survival rate were not different at 9 years between RP and HIFU.

INTRODUCTION AND OBJECTIVES: Current whole-gland therapy can lead to significant genitourinary side effects in men with localised prostate cancer. New ablative modalities have been shown to reduce such side-effects, but the degree to which erectile function, in particular, is impacted on by differing ablative strategies (whole-gland (WG) vs. hemiablation (HA) vs. focal therapy (FT)) has been poorly reported. We aimed to determine the functional changes in erectile function by comparing WG to organ-sparing high intensity focused ultrasound (HIFU). METHODS: A registry-based analysis of patients who underwent HIFU identified only those men having at least one complete IIEF-15 questionnaire at baseline and follow-up. Changes in total IIEF-15 scores were compared between WG and the tissue-preserving groups, and then between the HA and FT groups. Variation in ability to have penetrative intercourse was also evaluated (positive outcome defined as score 2 on IIEF-15 question 2). RESULTS: The HIFU registry incorporates data for 1405 men. After applying exclusion criteria, 169 were included in the final analysis: 84 WG and 85 tissue preserving (51 FT; 34 HA). WG ablation affected erectile function to a greater extent (IIEF-15 -10.3 19.0) than the tissue-preserving strategies (IIEF-15 -2.5 15.3; p 0.004). In addition, there was a trend (though not statistically significant) to better erectile function preservation after FT (IIEF-15 -0.6 15.7) when compared to HA (IIEF-15 -5.4 14.4; p 0.153). The proportions able to have erections sufficient for penetration showed a trend in favour of FT. The retrospective nature and important differences in baseline scores indicate possible selection biases. CONCLUSIONS: The extent of tissue preservation when treating prostatic disease seems to have a significant impact on postoperative erectile function. According to these results, organ-sparing strategies were better than WG ablation. There is an urgent need for prospective comparative effectiveness in this area.

Interest in integrating MRI into the prostate (CaP) cancer diagnostic pathway seems to be gaining ground [1]. Multiparametric (mp)MRI combines diffusion-weighted, dynamic contrast enhanced sequences or MR spectroscopy with conventional T2-weighted sequences. This has resulted in accuracy rates for the detection of clinically important CaP that compare favorably with established tests, such as X-ray mammography, for the detection of breast cancer [1,2]. However, its exact clinical utility remains the subject of legitimate professional disagreement. In this commentary, we attempt to highlight the areas in which mpMRI may have a role in improving the diagnosis and management of CaP.

Item does not contain fulltext Multiparametric magnetic resonance imaging (mpMRI) is increasingly being used earlier in the prostate cancer diagnostic pathway in order to detect and localize disease. Its results can be used to help decide on the indication, type, and localization of a prostate biopsy for cancer diagnosis. In addition, mpMRI has the potential to contribute information on the characterization, or aggressiveness, of detected cancers including tumor progression over time. There is considerable variation in the way results of different MRI sequences are reported. We conducted a review of scoring systems that have been used in the detection and characterization of prostate cancer. This revealed that existing scoring and reporting systems differ in purpose, scale, and range. We evaluate these differences in this review. This first step in collating all methods of scoring and reporting mpMRI will ultimately lead to consensus approaches to develop a standardized reporting scheme that can be widely adopted and validated to ensure comparability of research outputs and optimal clinical practice.

Men diagnosed with low-risk localized prostate cancer face a difficult decision between two extremes of care: active surveillance and radical therapies. The former entails living with the diagnosis of untreated cancer and the risk of progression; the latter provides a greater certainty of cancer control but with a significant side effect risk. Focal therapy potentially offers cancer control, without the side effect profile of radical therapies. Ablation is targeted at the cancer itself with preservation of surrounding normal tissue.

The concept of focal therapy, in its various modalities, is currently being explored within several clinical trials. All of these studies address the concept of targeting treatment only to the cancer, with sparing of normal tissue, in the aim of reducing treatment-related harm. However, the conduct of these trials varies significantly in terms of eligibility criteria, diagnostic investigations, treatment protocols, and follow-up strategies. This chapter explores the components of a focal therapy trial protocol and the possibilities for optimising and standardising its components in order to improve research outputs and comparison of results.