BackgroundFocal therapy as a treatment option for localized prostate cancer (PCa) is an increasingly popular and rapidly evolving field.ObjectiveTo gather expert opinion on patient selection, interventions, and meaningful outcome measures for focal therapy in clinical practice and trial design.Design, setting, and participantsFifteen experts in focal therapy followed a modified two-stage RAND/University of California, Los Angeles (UCLA) Appropriateness Methodology process. All participants independently scored 246 statements prior to rescoring at a face-to-face meeting. The meeting occurred in June 2013 at the Royal Society of Medicine, London, supported by the Wellcome Trust and the UK Department of Health.Outcome measurements and statistical analysisAgreement, disagreement, or uncertainty were calculated as the median panel score. Consensus was derived from the interpercentile range adjusted for symmetry level.Results and limitationsOf 246 statements, 154 (63%) reached consensus. Items of agreement included the following: patients with intermediate risk and patients with unifocal and multifocal PCa are eligible for focal treatment; magnetic resonance imaging–targeted or template-mapping biopsy should be used to plan treatment; planned treatment margins should be 5 mm from the known tumor; prostate volume or age should not be a primary determinant of eligibility; foci of indolent cancer can be left untreated when treating the dominant index lesion; histologic outcomes should be defined by targeted biopsy at 1 yr; residual disease in the treated area of ≤3 mm of Gleason 3 + 3 did not need further treatment; and focal retreatment rates of ≤20% should be considered clinically acceptable but subsequent whole-gland therapy deemed a failure of focal therapy. All statements are expert opinion and therefore constitute level 5 evidence and may not reflect wider clinical consensus.ConclusionsThe landscape of PCa treatment is rapidly evolving with new treatment technologies. This consensus meeting provides guidance to clinicians on current expert thinking in the field of focal therapy.Patient summaryIn this report we present expert opinion on patient selection, interventions, and meaningful outcomes for clinicians working in focal therapy for prostate cancer.

Passive acoustic mapping significantly outperformed the conventional hyperecho technique as an ultrasound-based HIFU monitoring method, as both a detector of lesion occurrence and a method of mapping the position of ablated tissue.

Objectives: To assess the safety and feasibility of high-intensity focused ultrasound (HIFU) ablation of liver tumours and to determine whether post-operative MRI correlates with intra-operative imaging. Methods: 31 patients were recruited into two ethically approved clinical trials (median age 64; mean BMI 26 kg m 22). Patients with liver tumours (primary or metastatic) underwent a single HIFU treatment monitored using intra-operative Bmode ultrasound. Follow-up consisted of radiology and histology (surgical trial) or radiology alone (radiology trial). Radiological follow-up was digital subtraction contrast-enhanced MRI. Results: Treatment according to protocol was possible in 30 of 31 patients. One treatment was abandoned because of equipment failure. Transient pain and superficial skin burns were seen in 81% (25/31) and 39% (12/31) of patients, respectively. One moderate skin burn occurred. One patient died prior to radiological follow-up. Radiological evidence of ablation was seen in 93% (27/29) of patients. Ablation accuracy was good in 89% (24/27) of patients. In three patients the zone of ablation lay #2 mm outside the tumour. The median cross-sectional area (CSA) of the zone of ablation was 5.0 and 5.1 cm 2 using intra-operative and post-operative imaging, respectively. The mean MRI:B-mode CSA ratio was 1.57 [95% confidence interval (CI)50.57-2.71]. There was positive correlation between MRI and B-mode CSA (Spearman's r50.48; 95% CI 0.11-0.73; p50.011) and the slope of linear regression was significantly non-zero (1.23; 95% CI50.68-1.77; p,0.0001). Conclusions: HIFU ablation of liver tumours is safe and feasible. HIFU treatment is accurate, and intra-operative assessment of treatment provides an accurate measure of the zone of ablation and correlates well with MRI follow-up. Colorectal cancer is one of the leading causes of mortality in Europe and the USA [1]. Of those diagnosed with colorectal cancer, 20-30% will have metastases in the liver at the time of diagnosis, and overall 50% will develop liver metastases during the course of their disease [2,3]. Despite this, at post-mortem, approximately one-quarter of patients are found to have metastases confined to the liver, and so the possibility of cure in such patients is available if these metastases can be treated effectively. Hepatic resection is feasible in only 10-25%, and although it is associated with an operative mortality of up to 5%, it can achieve 5-year survival rates in the region of 40% [4]. The favoured current alternative to surgery is combination chemotherapy, but this is associated with an objective response rate of just 20-50%, and relatively short median overall survival of approximately 12 months [5]. As a result there have been considerable efforts to provide minimally invasive alternatives to surgery for these patients. These alternatives include transarterial chemo-embolisation (TACE), direct percutaneous ethanol injection (PEI), and energy-based ablative techniques such as radiofrequency ablation (RFA), cryoablation, microwave th...

Study Type – Therapy (case series)
Level of Evidence 4 OBJECTIVE To determine whether primary extracorporeal high‐intensity focused ultrasound (HIFU) is safe, feasible and effective for managing small renal tumours. PATIENTS AND METHODS Although surgery currently remains the standard treatment for localized renal cell carcinoma (RCC), the increasing incidence of small renal cancers has led to a shift towards nephron‐sparing surgery, with associated morbidity in 20–25% of cases, and minimally invasive ablative therapies present an alternative management. HIFU results in ‘trackless’ homogenous tissue ablation and when administered via an extracorporeal device, is entirely noninvasive. The study comprised 17 patients (mean tumour size 2.5 cm) with radiologically suspicious renal tumours who underwent extracorporeal HIFU using the Model‐JC System (Chongqing HAIFUTM, China), under general anaesthesia with one overnight hospital stay. Real‐time diagnostic ultrasonography was used for targeting and monitoring. Patients were followed with a clinical review and gadolinium‐enhanced magnetic resonance imaging at 12 days and every 6 months for a mean of 36 months. The outcomes measures were patient morbidity and oncological efficacy of HIFU treatment. RESULTS Of the 17 patients, 15 were treated according to protocol; two procedures were abandoned due to intervening bowel. There were no major complications related to HIFU. Radiological evidence of ablation was apparent at 12 days in seven of the 15 patients. Before the 6‐month follow‐up one patient had surgery due to persisting central enhancement. Fourteen patients were evaluated at the 6‐month follow‐up; eight tumours had involuted (mean 12% decrease in tumour area). Four patients had irregular enhancement on imaging and had alternative therapies. Ten patients remain on follow‐up at a mean (range) of 36 (14–55) months after HIFU (mean 30% decrease in tumour area). There was central loss of enhancement in all. CONCLUSIONS Renal HIFU achieves stable lesions in two‐thirds of patients, with minimal morbidity, and might be appropriate in selected cases. Further trials with accurate histological follow‐up are essential to fully evaluate this novel technique.

In recent years high intensity focused ultrasound (HIFU) has received increasing interest as a non-invasive modality for the treatment of tumours of solid organs. Surgeons continue their quest to find the optimal technique whereby a diseased organ can be treated with a minimum of damage to the patient, while providing a comprehensive treatment to produce either cure or resolution of symptoms. Two of the areas in which HIFU is beginning to establish itself as a real therapeutic alternative, are in the treatment of abdominal and gynaecological disease. In this paper, we will review the literature available regarding the use of HIFU in the treatment of various organs: liver, kidney, pancreas, bladder, uterus and vulva.

Background Prostate cancer (PCa) is the most common cancer in men in the UK. Patients with intermediate-risk, clinically localised disease are offered radical treatments such as surgery or radiotherapy, which can result in severe side effects. A number of alternative partial ablation (PA) technologies that may reduce treatment burden are available; however the comparative effectiveness of these techniques has never been evaluated in a randomised controlled trial (RCT). Objectives To assess the feasibility of a RCT of PA using high-intensity focused ultrasound (HIFU) versus radical prostatectomy (RP) for intermediate-risk PCa and to test and optimise methods of data capture. Design We carried out a prospective, multicentre, open-label feasibility study to inform the design and conduct of a future RCT, involving a QuinteT Recruitment Intervention (QRI) to understand barriers to participation. Setting Five NHS hospitals in England. Participants Men with unilateral, intermediate-risk, clinically localised PCa. Interventions Radical prostatectomy compared with HIFU. Primary outcome measure The randomisation of 80 men. Secondary outcome measures Findings of the QRI and assessment of data capture methods. Results Eighty-seven patients consented to participate by 31 March 2017 and 82 men were randomised by 4 May 2017 (41 men to the RP arm and 41 to the HIFU arm). The QRI was conducted in two iterative phases: phase I identified a number of barriers to recruitment, including organisational challenges, lack of recruiter equipoise and difficulties communicating with patients about the study, and phase II comprised the development and delivery of tailored strategies to optimise recruitment, including group training, individual feedback and ‘tips’ documents. At the time of data extraction, on 10 October 2017, treatment data were available for 71 patients. Patient characteristics were similar at baseline and the rate of return of all clinical case report forms (CRFs) was 95%; the return rate of the patient-reported outcome measures (PROMs) questionnaire pack was 90.5%. Centres with specific long-standing expertise in offering HIFU as a routine NHS treatment option had lower recruitment rates (Basingstoke and Southampton) – with University College Hospital failing to enrol any participants – than centres offering HIFU in the trial context only. Conclusions Randomisation of men to a RCT comparing PA with radical treatments of the prostate is feasible. The QRI provided insights into the complexities of recruiting to this surgical trial and has highlighted a number of key lessons that are likely to be important if the study progresses to a main trial. A full RCT comparing clinical effectiveness, cost-effectiveness and quality-of-life outcomes between radical treatments and PA is now warranted. Future work Men recruited to the feasibility study will be followed up for 36 months in accordance with the protocol. We will design a full RCT, taking into account the lessons learnt from this study. CRFs will be streamlined, and the length and frequency of PROMs and resource use diaries will be reviewed to reduce the burden on patients and research nurses and to optimise data completeness. Trial registration Current Controlled Trials ISRCTN99760303. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 52. See the NIHR Journals Library website for further project information.

IntroductionFocal therapy offers the possibility of cancer control, without the side effect profile of radical therapies. Early single centre prospective development studies using high intensity focused ultrasound (HIFU) have demonstrated encouraging genitourinary functional preservation and short-term cancer control. Large multi-centre trials are required to evaluate medium-term cancer control and reproduce functional recovery. We describe the study design of an investigator-led UK multi-centre, single arm trial using HIFU to deliver focal therapy for men with localised prostate cancer.MethodsOne-hundred and forty men with histologically proven localised low or intermediate risk prostate cancer (PSA < 15, Gleason ≤ 7, ≤ T2cN0M0) will undergo precise characterisation of the prostate using a combination of multi-parametric (mp)MRI and transperineal template prostate mapping (TPM) biopsies. Unilateral dominant tumours, the so-called index lesion, will be eligible for treatment provided the contra-lateral side is free of ‘clinically significant’ disease (as defined by Gleason ≥ 7 or maximum cancer core length ≥ 4 mm). Patients will receive focal therapy using HIFU (Sonablate 500®). Treatment effect will be assessed by targeted biopsies of the treated area and TPM biopsies at 36-months.ResultsPrimary outcome is the absence of clinically significant disease based on 36-month post-treatment TPM biopsies. Secondary outcomes address a) genitourinary function using validated patient questionnaires (IPSS, IPSS-QoL, IIEF-15, EPIC-Urinary, EPIC-Bowel, FACT-P, EQ-5D), b) the predictive validity of imaging, and c) risk factors for treatment failure.ConclusionsINDEX will be the first multi-centre, medium term follow-up trial to evaluate the outcomes of a tissue preserving strategy for men with localised prostate cancer using the TPM-ablate-TPM strategy.

Tissue-preserving focal therapies, such as brachytherapy, cryotherapy, high-intensity focused ultrasound and photodynamic therapy, aim to target individual cancer lesions rather than the whole prostate. These treatments have emerged as potential interventions for localized prostate cancer to reduce treatment-related adverse-effects associated with whole-gland treatments, such as radical prostatectomy and radiotherapy. In this article, the Prostate Cancer RCT Consensus Group propose that a novel cohort-embedded randomized controlled trial (RCT) would provide a means to study men with clinically significant localized disease, which we defined on the basis of PSA level (≤ 15 ng/ml or ≤ 20 ng/ml), Gleason grade (Gleason pattern ≤ 4 + 4 or ≤ 4 + 3) and stage (≤ cT2cN0M0). This RCT should recruit men who stand to benefit from treatment, with the control arm being whole-gland surgery or radiotherapy. Composite outcomes measuring rates of local and systemic salvage therapies at 3-5 years might best constitute the basis of the primary outcome on which to change practice.