Utilizing low-cost purple coneflower (Echniacea purpurea) marc for competitive sorption of 152+154Eu(III), 60Co(II) and 134Cs(I) radionuclides.

Echinacea purpurea marc (EPM), a residual of echinacea herb after the extraction process, was used as a natural low-cost sorbent for competitive sorption of 152+154Eu(III), 60Co(II) and 134Cs(I) radionuclides. The EPM was ground to prepare it for use in the sorption process. The variables influencing the sorption process were assessed, including pH, contact time, concentrations of metal ions, and temperature. EPM was characterized by different analytical instruments such as FTIR, SEM, XRD, and DTA/TGA. pH 4.0 was selected as the ideal pH value for competitive sorption of the studied ions. Adsorption kinetics data found that the sorption followed a pseudo-second-order model. The adsorption isotherm data was significantly better suited by the Langmuir isotherms in the case of Eu(III) ions while following Freundlich in the case of Co(II) and Cs(I) ions. Positive ΔHo values confirm the endothermic character of metal ion sorption onto EPM. The loading efficiencies of Eu(III), Co(II), and Cs(I) ions in the EPM column were 66.67%, 9.59%, and 4.81%, respectively. The EPM is a cost-effective and efficient separation of Eu(III) ions more than Cs(I) and Co(II) ions. Therefore, in the future, it will be a starting point for the separation of trivalent elements of lanthanide ions.

The Role of Multiparametric MRI and MRI-targeted Biopsy in the Diagnosis of Radiorecurrent Prostate Cancer: An Analysis from the FORECAST Trial.

BACKGROUND: The role of multiparametric magnetic resonance imaging (MRI) for detecting recurrent prostate cancer after radiotherapy is unclear. OBJECTIVE: To evaluate MRI and MRI-targeted biopsies for detecting intraprostatic cancer recurrence and planning for salvage focal ablation. DESIGN, SETTING, AND PARTICIPANTS: FOcal RECurrent Assessment and Salvage Treatment (FORECAST; NCT01883128) was a prospective cohort diagnostic study that recruited 181 patients with suspected radiorecurrence at six UK centres (2014 to 2018); 144 were included here. INTERVENTION: All patients underwent MRI with 5 mm transperineal template mapping biopsies; 84 had additional MRI-targeted biopsies. MRI scans with Likert scores of 3 to 5 were deemed suspicious. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: First, the diagnostic accuracy of MRI was calculated. Second, the pathological characteristics of MRI-detected and MRI-undetected tumours were compared using the Wilcoxon rank sum test and chi-square test for trend. Third, four biopsy strategies involving an MRI-targeted biopsy alone and with systematic biopsies of one to two other quadrants were studied. Fisher's exact test was used to compare MRI-targeted biopsy alone with the best other strategy for the number of patients with missed cancer and the number of patients with cancer harbouring additional tumours in unsampled quadrants. Analyses focused primarily on detecting cancer of any grade or length. Last, eligibility for focal therapy was evaluated for men with localised (≤T3bN0M0) radiorecurrent disease. RESULTS AND LIMITATIONS: Of 144 patients, 111 (77%) had cancer detected on biopsy. MRI sensitivity and specificity at the patient level were 0.95 (95% confidence interval [CI] 0.92 to 0.99) and 0.21 (95% CI 0.07 to 0.35), respectively. At the prostate quadrant level, 258/576 (45%) quadrants had cancer detected on biopsy. Sensitivity and specificity were 0.66 (95% CI 0.59 to 0.73) and 0.54 (95% CI 0.46 to 0.62), respectively. At the quadrant level, compared with MRI-undetected tumours, MRI-detected tumours had longer maximum cancer core length (median difference 3 mm [7 vs 4 mm]; 95% CI 1 to 4 mm, p < 0.001) and a higher grade group (p = 0.002). Of the 84 men who also underwent an MRI-targeted biopsy, 73 (87%) had recurrent cancer diagnosed. Performing an MRI-targeted biopsy alone missed cancer in 5/73 patients (7%; 95% CI 3 to 15%); with additional systematic sampling of the other ipsilateral and contralateral posterior quadrants (strategy 4), 2/73 patients (3%; 95% CI 0 to 10%) would have had cancer missed (difference 4%; 95% CI -3 to 11%, p = 0.4). If an MRI-targeted biopsy alone was performed, 43/73 (59%; 95% CI 47 to 69%) patients with cancer would have harboured undetected additional tumours in unsampled quadrants. This reduced but only to 7/73 patients (10%; 95% CI 4 to 19%) with strategy 4 (difference 49%; 95% CI 36 to 62%, p < 0.0001). Of 73 patients, 43 (59%; 95% CI 47 to 69%) had localised radiorecurrent cancer suitable for a form of focal ablation. CONCLUSIONS: For patients with recurrent prostate cancer after radiotherapy, MRI and MRI-targeted biopsy, with or without perilesional sampling, will diagnose cancer in the majority where present. MRI-undetected cancers, defined as Likert scores of 1 to 2, were found to be smaller and of lower grade. However, if salvage focal ablation is planned, an MRI-targeted biopsy alone is insufficient for prostate mapping; approximately three of five patients with recurrent cancer found on an MRI-targeted biopsy alone harboured further tumours in unsampled quadrants. Systematic sampling of the whole gland should be considered in addition to an MRI-targeted biopsy to capture both MRI-detected and MRI-undetected disease. PATIENT SUMMARY: After radiotherapy, magnetic resonance imaging (MRI) is accurate for detecting recurrent prostate cancer, with missed cancer being smaller and of lower grade. Targeting a biopsy to suspicious areas on MRI results in a diagnosis of cancer in most patients. However, for every five men who have recurrent cancer, this targeted approach would miss cancers elsewhere in the prostate in three of these men. If further focal treatment of the prostate is planned, random biopsies covering the whole prostate in addition to targeted biopsies should be considered so that tumours are not missed.

Focal therapy versus radical prostatectomy and external beam radiotherapy as primary treatment options for non-metastatic prostate cancer: results of a cost-effectiveness analysis.

AIMS: Focal therapy treats individual areas of tumour in non-metastatic prostate cancer in patients unsuitable for active surveillance. The aim of this work was to evaluate the cost-effectiveness of focal therapy versus prostatectomy and external beam radiotherapy (EBRT). MATERIALS AND METHODS: A Markov cohort health state transition model with four health states (stable disease, local recurrence, metastatic disease and death) was created, evaluating costs and utilities over a 10-year time horizon for patients diagnosed with non-metastatic prostate cancer. National Health Service (NHS) for England perspective was used, based on direct healthcare costs. Clinical transition probabilities were derived from prostate cancer registries in patients undergoing radical prostatectomy, EBRT and focal therapy using cryotherapy (Boston Scientific) or high-intensity focused ultrasound (HIFU) (Sonablate). Propensity score matching was used to ensure that at-risk populations were comparable. Variables included age, prostate-specific antigen (PSA), International Society of Urological Pathology (ISUP) grade group, maximum cancer core length (mm), T-stage and year of treatment. RESULTS: Focal therapy was associated with a lower overall cost and higher quality-adjusted life year (QALY) gains than either prostatectomy or EBRT, dominating both treatment strategies. Positive incremental net monetary benefit (NMB) values confirm focal therapy as cost-effective versus the alternatives at a willingness to pay (WTP) threshold of £30,000/QALY. One-way deterministic sensitivity analyses revealed consistent results. LIMITATIONS: Data used to calculate the transition probabilities were derived from a limited number of hospitals meaning that other potential treatment options were excluded. Limited data were available on later outcomes and none on quality of life data, therefore, literature-based estimates were used. CONCLUSIONS: Cost-effectiveness modelling demonstrates use of focal therapy (cryotherapy or HIFU) is associated with greater QALY gains at a lower overall cost than either radical prostatectomy or EBRT, representing good value for money in the NHS.

Focal therapy can be used for the primary treatment of individual areas of cancer in those patients with prostate cancer whose disease has not spread (localized or non-metastatic prostate cancer) and whose disease is unsuitable for active monitoring. Focal therapy in these patients results in similar control of the cancer to more invasive therapies, such as surgical removal of the prostate and radiotherapy, with the benefit of fewer sexual, urinary and rectal side effects. This work considered whether using focal therapy (either freezing the cancer cells using cryotherapy or using high-intensity focused ultrasound [HIFU] to destroy cancer cells) was good value for money in the National Health Service (NHS) compared with surgery or radiotherapy. An economic model was developed which considered the relative impact of treatment with focal therapies, surgery or radiotherapy within the NHS in England. Previously collected information from people undergoing treatment for their prostate cancer, together with published literature and clinical opinion, was used within the model to predict the treatment pathway, costs incurred and the results of treatment in terms of patient benefits (effectiveness and quality of life). The model showed that focal therapy using either cryotherapy or HIFU was associated with a lower overall cost and higher patient benefit than either surgery or radiotherapy, indicating that focal therapy represents good value for money in the NHS.

External validation of a risk model predicting failure of salvage focal ablation for prostate cancer.

OBJECTIVES: To externally validate a published model predicting failure within 2 years after salvage focal ablation in men with localised radiorecurrent prostate cancer using a prospective, UK multicentre dataset. PATIENTS AND METHODS: Patients with biopsy-confirmed ≤T3bN0M0 cancer after previous external beam radiotherapy or brachytherapy were included from the FOcal RECurrent Assessment and Salvage Treatment (FORECAST) trial (NCT01883128; 2014-2018; six centres), and from the high-intensity focussed ultrasound (HIFU) Evaluation and Assessment of Treatment (HEAT) and International Cryotherapy Evaluation (ICE) UK-based registries (2006-2022; nine centres). Eligible patients underwent either salvage focal HIFU or cryotherapy, with the choice based predominantly on anatomical factors. Per the original multivariable Cox regression model, the predicted outcome was a composite failure outcome. Model performance was assessed at 2 years post-salvage with discrimination (concordance index [C-index]), calibration (calibration curve and slope), and decision curve analysis. For the latter, two clinically-reasonable risk threshold ranges of 0.14-0.52 and 0.26-0.36 were considered, corresponding to previously published pooled 2-year recurrence-free survival rates for salvage local treatments. RESULTS: A total of 168 patients were included, of whom 84/168 (50%) experienced the primary outcome in all follow-ups, and 72/168 (43%) within 2 years. The C-index was 0.65 (95% confidence interval 0.58-0.71). On graphical inspection, there was close agreement between predicted and observed failure. The calibration slope was 1.01. In decision curve analysis, there was incremental net benefit vs a 'treat all' strategy at risk thresholds of ≥0.23. The net benefit was therefore higher across the majority of the 0.14-0.52 risk threshold range, and all of the 0.26-0.36 range. CONCLUSION: In external validation using prospective, multicentre data, this model demonstrated modest discrimination but good calibration and clinical utility for predicting failure of salvage focal ablation within 2 years. This model could be reasonably used to improve selection of appropriate treatment candidates for salvage focal ablation, and its use should be considered when discussing salvage options with patients. Further validation in larger, international cohorts with longer follow-up is recommended.

Evaluation of Outcomes Following Focal Ablative Therapy for Treatment of Localized Clinically Significant Prostate Cancer in Patients >70 Years: A Multi-institute, Multi-energy 15-Year Experience.

PURPOSE: In older patients who do not wish to undergo watchful waiting, focal therapy could be an alternative to the more morbid radical treatment. We evaluated the role of focal therapy in patients 70 years and older as an alternative management modality. MATERIALS AND METHODS: A total of 649 patients across 11 UK sites receiving focal high-intensity focused ultrasound or cryotherapy between June 2006 and July 2020 reported within the UK-based HEAT (HIFU Evaluation and Assessment of Treatment) and ICE (International Cryotherapy Evaluation) registries were evaluated. Primary outcome was failure-free survival, defined by need for more than 1 focal reablation, progression to radical treatment, development of metastases, need for systemic treatment, or prostate cancer-specific death. This was compared to the failure-free survival in patients undergoing radical treatment via a propensity score weighted analysis. RESULTS: Median age was 74 years (IQR: 72, 77) and median follow-up 24 months (IQR: 12, 41). Sixty percent had intermediate-risk disease and 35% high-risk disease. A total of 113 patients (17%) required further treatment. Sixteen had radical treatment and 44 required systemic treatment. Failure-free survival was 82% (95% CI: 76%-87%) at 5 years. Comparing patients who had radical therapy to those who had focal therapy, 5-year failure-free survival was 96% (95% CI: 93%-100%) and 82% (95% CI: 75%-91%) respectively (P < .001). Ninety-three percent of those in the radical treatment arm had received radiotherapy as their primary treatment with its associated use of androgen deprivation therapy, thereby leading to potential overestimation of treatment success in the radical treatment arm, especially given the similar metastases-free and overall survival rates seen. CONCLUSIONS: We propose focal therapy to be an effective management option for the older or comorbid patient who is unsuitable for or not willing to undergo radical treatment.

Radiation synthesis of chitosan/poly(acrylamide-co-maleic acid) hydrogel for the removal of 152+154Eu (III) ions.

Using gamma radiation, a chitosan-poly (acrylamide-co-maleic acid) hydrogel was created by copolymerizing acrylamide and maleic acid onto the surface of chitosan. The shape, thermal stability, and structure of the hydrogel were confirmed by Fourier transform infrared analysis, scanning electron microscopy, thermogravimetric analysis, and differential thermal analysis. The batch adsorption of 152+154Eu(III) ions from an aqueous solution showed a rapid initial uptake with an equilibrium time of 24 h at pH (∼4). The Langmuir, Freundlich, Temkin, and Dubinin-Radushkevich isotherm models were used to study the adsorption equilibrium data. The adsorption behavior of 152+154Eu(III) ions closely followed the Langmuir isotherm, exhibiting a maximum adsorption capacity of 144.96 mg/g. The adsorption kinetics of 152+154Eu(III) ions are best described by the pseudo-second order model. The thermodynamic parameters were studied and revealed that the adsorption process was spontaneous, exothermic, and favorable at a lower temperature. 0.1 M HCl and AlCl3 desorbed 152+154Eu(III) ions with 97.09% and 88.63%, respectively. Hence, the hydrogel will serve as a starting point for the adsorption of trivalent lanthanide ions in the future.

Radiation synthesis and characterization of starch-acrylic acid-nanohalloysite composite for the removal of Co(II) ions from aqueous solutions.

In this study, gamma rays were used as an initiator to prepare starch-acrylic acid/nanohalloysite, P(Stc-AA/NHal) composite for the removal of Co(II) from aqueous solutions. The characteristic peaks of P(Stc-AA/NHal) composite was confirmed by Fourier transform infrared spectroscopic analysis (FTIR). The morphological structure was examined using a scanning electron microscope (SEM). Differential thermal analysis (DTA) and thermogravimetric analysis (TGA) were also used to characterize the composite and demonstrate its high thermal stability. Using a batch sorption technique and 60Co as a radiotracer, the P(Stc-AA/NHal) composite was evaluated for Co(II) ions removal from aqueous solutions. The effect of pH, contact time, metal ion concentration, and temperature on Co(II) ions sorption were studied. The kinetic data of adsorption fit accurately with the pseudo-second-order adsorption model. Finally, the equilibrium adsorption results fitted the Langmuir isotherm model very well. The highest adsorption capacity measured was 103.6 mg g-1.

Real-world Early Outcomes and Retreatment Rates Following Water Vapour Ablative Therapy for Symptomatic Benign Prostatic Hyperplasia.

Background: Rezum water vapour ablation is an effective minimally invasive surgical therapy for the treatment of bladder outflow obstruction. Objective: To present early outcomes and reoperation rates after Rezum, including an analysis of retreatment rates to gain an insight into optimal patient selection and the durability of the procedure. Design setting and participants: Data were prospectively collected for consecutive patients undergoing Rezum for symptomatic benign prostatic hyperplasia between March 2017 and January 2020 at two hospital sites. Intervention: Rezum treatment of the prostate. Outcome measurements and statistical analysis: Patients were reviewed at 6 wk and 3, 6, and 12 mo after their Rezum procedure. We evaluated changes in urinary symptoms and the retreatment rate. Results and limitations: A total of 461 patients undergoing Rezum were analysed. The mean (±standard deviation) follow-up duration was 16.7 ± 10.4 mo. The mean patient age was 67.5 ± 7.8 yr and the mean prostate volume was 56.5 ± 24.0 ml. There was a significant improvement in mean maximum flow rate and postvoid residual volume and in International Prostate Symptom Score and quality-of-life scores (p < 0.0001). During the follow-up period, 21 patients (4.6%) required retreatment, of which 11 cases (2.4%) were within the first year. The retreatments included eight bladder neck incisions or resections, six transurethral resections of the prostate, four Greenlight laser photoselective vaporisations of the prostate, and three Rezum procedures. The median length of time to a further operation was 11.5 mo (range 3-34). The most common findings at reoperation were an inadequately treated median lobe, an obstructing bladder neck, and in some cases asymmetry of the prostate cavity or recesses within the prostate gland. Conclusions: This study demonstrates that the beneficial effects of Rezum observed in the pivotal phase 2 randomised study are transferable to a real-world population with a comparable early retreatment rate. A range of procedures were used for retreatment. The factors dictating which option to select were based on patient concerns regarding side effects, gland volume, symptom profile, and cystoscopy findings. Patient summary: We investigated outcomes for patients undergoing Rezum, a water vapour treatment to reduce the size of the prostate in men with obstruction of the bladder outlet because of benign prostate enlargement. This technique yields significant improvements in symptoms and preserves sexual function. The proportion of men needing retreatment was 2.4% in the first year after their Rezum procedure.

Magnetic Resonance Imaging and Targeted Biopsies Compared to Transperineal Mapping Biopsies Before Focal Ablation in Localised and Metastatic Recurrent Prostate Cancer After Radiotherapy.

BACKGROUND: Recurrent prostate cancer after radiotherapy occurs in one in five patients. The efficacy of prostate magnetic resonance imaging (MRI) in recurrent cancer has not been established. Furthermore, high-quality data on new minimally invasive salvage focal ablative treatments are needed. OBJECTIVE: To evaluate the role of prostate MRI in detection of prostate cancer recurring after radiotherapy and the role of salvage focal ablation in treating recurrent disease. DESIGN, SETTING, AND PARTICIPANTS: The FORECAST trial was both a paired-cohort diagnostic study evaluating prostate multiparametric MRI (mpMRI) and MRI-targeted biopsies in the detection of recurrent cancer and a cohort study evaluating focal ablation at six UK centres. A total of 181 patients were recruited, with 155 included in the MRI analysis and 93 in the focal ablation analysis. INTERVENTION: Patients underwent choline positron emission tomography/computed tomography and a bone scan, followed by prostate mpMRI and MRI-targeted and transperineal template-mapping (TTPM) biopsies. MRI was reported blind to other tests. Those eligible underwent subsequent focal ablation. An amendment in December 2014 permitted focal ablation in patients with metastases. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcomes were the sensitivity of MRI and MRI-targeted biopsies for cancer detection, and urinary incontinence after focal ablation. A key secondary outcome was progression-free survival (PFS). RESULTS AND LIMITATIONS: Staging whole-body imaging revealed localised cancer in 128 patients (71%), with involvement of pelvic nodes only in 13 (7%) and metastases in 38 (21%). The sensitivity of MRI-targeted biopsy was 92% (95% confidence interval [CI] 83-97%). The specificity and positive and negative predictive values were 75% (95% CI 45-92%), 94% (95% CI 86-98%), and 65% (95% CI 38-86%), respectively. Four cancer (6%) were missed by TTPM biopsy and six (8%) were missed by MRI-targeted biopsy. The overall MRI sensitivity for detection of any cancer was 94% (95% CI 88-98%). The specificity and positive and negative predictive values were 18% (95% CI 7-35%), 80% (95% CI 73-87%), and 46% (95% CI 19-75%), respectively. Among 93 patients undergoing focal ablation, urinary incontinence occurred in 15 (16%) and five (5%) had a grade ≥3 adverse event, with no rectal injuries. Median follow-up was 27 mo (interquartile range 18-36); overall PFS was 66% (interquartile range 54-75%) at 24 mo. CONCLUSIONS: Patients should undergo prostate MRI with both systematic and targeted biopsies to optimise cancer detection. Focal ablation for areas of intraprostatic recurrence preserves continence in the majority, with good early cancer control. PATIENT SUMMARY: We investigated the role of magnetic resonance imaging (MRI) scans of the prostate and MRI-targeted biopsies in outcomes after cancer-targeted high-intensity ultrasound or cryotherapy in patients with recurrent cancer after radiotherapy. Our findings show that these patients should undergo prostate MRI with both systematic and targeted biopsies and then ablative treatment focused on areas of recurrent cancer to preserve their quality of life. This trial is registered at ClinicalTrials.gov as NCT01883128.

Cancer Control Outcomes Following Focal Therapy Using High-intensity Focused Ultrasound in 1379 Men with Nonmetastatic Prostate Cancer: A Multi-institute 15-year Experience.

BACKGROUND: Focal therapy aims to treat areas of cancer to confer oncological control whilst reducing treatment-related functional detriment. OBJECTIVE: To report oncological outcomes and adverse events following focal high-intensity focused ultrasound (HIFU) for treating nonmetastatic prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: An analysis of 1379 patients with ≥6 mo of follow-up prospectively recorded in the HIFU Evaluation and Assessment of Treatment (HEAT) registry from 13 UK centres (2005-2020) was conducted. Five or more years of follow-up was available for 325 (24%) patients. Focal HIFU therapy used a transrectal ultrasound-guided device (Sonablate; Sonacare Inc., Charlotte, NC, USA). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Failure-free survival (FFS) was primarily defined as avoidance of no evidence of disease to require salvage whole-gland or systemic treatment, or metastases or prostate cancer-specific mortality. Differences in FFS between D'Amico risk groups were determined using a log-rank analysis. Adverse events were reported using Clavien-Dindo classification. RESULTS AND LIMITATIONS: The median (interquartile range) age was 66 (60-71) yr and prostate-specific antigen was 6.9 (4.9-9.4) ng/ml with D'Amico intermediate risk in 65% (896/1379) and high risk in 28% (386/1379). The overall median follow-up was 32 (17-58) mo; for those with ≥5 yr of follow-up, it was 82 (72-94). A total of 252 patients had repeat focal treatment due to residual or recurrent cancer; overall 92 patients required salvage whole-gland treatment. Kaplan-Meier 7-yr FFS was 69% (64-74%). Seven-year FFS in intermediate- and high-risk cancers was 68% (95% confidence interval [CI] 62-75%) and 65% (95% CI 56-74%; p = 0.3). Clavien-Dindo >2 adverse events occurred in 0.5% (7/1379). The median 10-yr follow-up is lacking. CONCLUSIONS: Focal HIFU in carefully selected patients with clinically significant prostate cancer, with six and three of ten patients having, respectively, intermediate- and high-risk cancer, has good cancer control in the medium term. PATIENT SUMMARY: Focal high-intensity focused ultrasound treatment to areas of prostate with cancer can provide an alternative to treating the whole prostate. This treatment modality has good medium-term cancer control over 7 yr, although 10-yr data are not yet available.

Conventional radical versus focal treatment for localised prostate cancer: a propensity score weighted comparison of 6-year tumour control.

BACKGROUND: For localised prostate cancer, focal therapy offers an organ-sparing alternative to radical treatments (radiotherapy or prostatectomy). Currently, there is no randomised comparative effectiveness data evaluating cancer control of both strategies. METHODS: Following the eligibility criteria PSA < 20 ng/mL, Gleason score ≤ 7 and T-stage ≤ T2c, we included 830 radical (440 radiotherapy, 390 prostatectomy) and 530 focal therapy (cryotherapy, high-intensity focused ultrasound or high-dose-rate brachytherapy) patients treated between 2005 and 2018 from multicentre registries in the Netherlands and the UK. A propensity score weighted (PSW) analysis was performed to compare failure-free survival (FFS), with failure defined as salvage treatment, metastatic disease, systemic treatment (androgen deprivation therapy or chemotherapy), or progression to watchful waiting. The secondary outcome was overall survival (OS). Median (IQR) follow-up in each cohort was 55 (28-83) and 62 (42-83) months, respectively. RESULTS: At baseline, radical patients had higher PSA (10.3 versus 7.9) and higher-grade disease (31% ISUP 3 versus 11%) compared to focal patients. After PSW, all covariates were balanced (SMD < 0.1). 6-year weighted FFS was higher after radical therapy (80.3%, 95% CI 73.9-87.3) than after focal therapy (72.8%, 95% CI 66.8-79.8) although not statistically significant (p = 0.1). 6-year weighted OS was significantly lower after radical therapy (93.4%, 95% CI 90.1-95.2 versus 97.5%, 95% CI 94-99.9; p = 0.02). When compared in a three-way analysis, focal and LRP patients had a higher risk of treatment failure than EBRT patients (p < 0.001), but EBRT patients had a higher risk of mortality than focal patients (p = 0.008). CONCLUSIONS: Within the limitations of a cohort-based analysis in which residual confounders are likely to exist, we found no clinically relevant difference in cancer control conferred by focal therapy compared to radical therapy at 6 years.

Focal therapy compared to radical prostatectomy for non-metastatic prostate cancer: a propensity score-matched study.

INTRODUCTION: Focal therapy (FT) ablates areas of prostate cancer rather than treating the whole gland. We compared oncological outcomes of FT to radical prostatectomy (RP). METHODS: Using prospective multicentre databases of 761 FT and 572 RP cases (November/2005-September/2018), patients with PSA < 20 ng/ml, Gleason

Clinical recommendations in the management of advanced prostate cancer: International Gastrointestinal, Liver and Uro-oncology (IGILUC 2019) experts.

PURPOSE: Advancements in the diagnosis and treatment of prostate cancer (PC) have rapidly progressed through the past years. Various factors should be taken into account while treating individual patients to ensure optimal and careful decision making. The purpose of this consensus review is to summarize the current practice patterns when managing patients with advanced prostate cancer (APC) as there is still a lack of or very limited evidence on its clinical management in some areas. METHODS: Pre-defined questions were shared with experts prior to the consensus session that took place in Cairo, Egypt in April 2019 during the 8th International gastrointestinal, liver and uro-oncology conference (IGILUC). Voting was based mainly on the expert opinions of the panel after a thorough discussion and review of available evidence from guidelines or best evidence available concerning the topic at hand. RESULTS: A strong consensus or unanimity was reached on 47% of the proposed questions. Notably, the panelists reached consensus on several topics based on high-level expert opinion. These findings contribute in several ways to our understanding of the management of PC and provide a basis for future recommendations. There was also a lack of consensus on other several topics, which suggests the need for further supporting data addressing these knowledge gaps. CONCLUSION: This review offers a thorough understanding of APC practice and offers insight on the various opinions shared amongst experts in the field that can serve as guidance regionally and deepens our understanding of disease management globally.

Focal High-intensity Focussed Ultrasound Partial Gland Ablation for the Treatment of Localised Prostate Cancer: A Report of Medium-term Outcomes From a Single-center in the United Kingdom.

OBJECTIVE: To report our intermediate outcomes of the use of focal ablation for treating significant unilateral prostate cancer. This technique was adopted in our center 10 years ago. With improving diagnostic accuracy of index prostate cancer lesions and a low side-effect profile, use of focal high intensity focused ultrasound (HIFU) ablation is increasing. METHODS: Patients were diagnosed using prostate specific antigen (PSA), multiparametric magnetic resonance imaging, and template transperineal biopsies. Focal ablation of significant cancer was performed with the Sonablate device. Follow-up consisted of magnetic resonance imaging scanning, PSA, validated questionnaires, biopsy for cause, and redo HIFU if required as part of the treatment strategy. RESULTS: A total of 107 men underwent focal HIFU. In total, 88% had intermediate/high risk disease, and the mean pre-HIFU PSA was 7.7. A total of 31% had high volume Gleason 6 disease, 55% had Gleason 3+4 disease, and 13% had Gleason ≥ 4+3 disease. In total, 54 men received a hemiablation, 10 a focal ablation, and 43 a quadrant ablation. Median follow-up was 30 months, subjects' PSA dropped to an average 71% nadir. A total of 8% had biochemical recurrence and 11% required adjuvant treatment. Freedom from additional procedures for clinically significant recurrent disease, including redo-HIFU, was 85.5%. Postoperative complications included 1% new use of pads, 1.9% urethral stricture, 2.8% post-HIFU TURP, and new onset ED of 14%. CONCLUSION: In a carefully chosen cohort of patients for focal HIFU our results suggest acceptable oncological control with minimal postoperative morbidity. Further studies are required to establish this technique as a less morbid alternative to radical therapy.

Partial ablation versus radical prostatectomy in intermediate-risk prostate cancer: the PART feasibility RCT.

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.

Overcoming difficulties with equipoise to enable recruitment to a randomised controlled trial of partial ablation vs radical prostatectomy for unilateral localised prostate cancer.

OBJECTIVE: To describe how clinicians conceptualised equipoise in the PART (Partial prostate Ablation vs Radical prosTatectomy in intermediate-risk unilateral clinically localised prostate cancer) feasibility study and how this affected recruitment. SUBJECTS AND METHODS: PART included a QuinteT Recruitment Intervention (QRI) to optimise recruitment. Phase I aimed to understand recruitment, and included: scrutinising recruitment data, interviewing the trial management group and recruiters (n = 13), and audio-recording recruitment consultations (n = 64). Data were analysed using qualitative content and thematic analysis methods. In Phase II, strategies to improve recruitment were developed and delivered. RESULTS: Initially many recruiters found it difficult to maintain a position of equipoise and held preconceptions about which treatment was best for particular patients. They did not feel comfortable about approaching all eligible patients, and when the study was discussed, biases were conveyed through the use of terminology, poorly balanced information, and direct treatment recommendations. Individual and group feedback led to presentations to patients becoming clearer and enabled recruiters to reconsider their sense of equipoise. Although the precise impact of the QRI alone cannot be determined, recruitment increased (from a mean [range] of 1.4 [0-4] to 4.5 [0-12] patients/month) and the feasibility study reached its recruitment target. CONCLUSION: Although clinicians find it challenging to recruit patients to a trial comparing different contemporary treatments for prostate cancer, training and support can enable recruiters to become more comfortable with conveying equipoise and providing clearer information to patients.

Long-Term Outcomes of Laparoscopic Nephroureterectomy with Transurethral Circumferential Excision of the Ureteral Orifice for Urothelial Carcinoma.

INTRODUCTION: When performing open or laparoscopic nephroureterectomy (LNU), the optimal way to excise the distal ureter remains controversial. There are concerns that primary endoscopic detachment of the intramural ureter is associated with adverse outcomes. Existing studies have limited number of patients and inadequate oncologic follow-up. We provide our institutions experience of this technique. MATERIALS AND METHODS: Data were collected prospectively on 59 patients (37 men) who underwent LNU for a 10-year period at a single center using a standardized technique: initial endoscopic circumferential release of the distal ureter and bladder cuff followed by retroperitoneal en bloc LNU. RESULTS: Patients had a mean age of 67 years and Charlson score of 2. One case was converted to open surgery. Mean operative time was 194 minutes with estimated blood loss of 125 mL. Three patients (5%) required a blood transfusion. Mean in-patient stay was 3 days. Forty-six patients had urothelial carcinoma. Seventy-one percent of patients had high-grade disease (n = 33) and 21% had distal ureteral disease (n = 10). One patient required open excision of recurrence at the site of the excised ureteral orifice and remains disease free 5 years later. Five-year cancer-specific survival was 100% for patients with stages pTa (n = 7) and pT1 (n = 14), 93% for stage pT2 (n = 7) disease, and 49% for patients with stage pT3 (n = 18) disease. CONCLUSIONS: Transurethral resection of the ureteral orifice during LNU achieves acceptable long-term oncologic outcomes while minimizing perioperative morbidity and in-patient stay. This represents the largest single-center study of this technique to date.