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.

Combination of verteporfin-photodynamic therapy with 5-aza-2'-deoxycytidine enhances the anti-tumour immune response in triple negative breast cancer.

Introduction: Triple negative breast cancer (TNBC) is a subtype of breast cancer characterised by its high tumourigenic, invasive, and immunosuppressive nature. Photodynamic therapy (PDT) is a focal therapy that uses light to activate a photosensitizing agent and induce a cytotoxic effect. 5-aza-2'-deoxycytidine (5-ADC) is a clinically approved immunomodulatory chemotherapy agent. The mechanism of the combination therapy using PDT and 5-ADC in evoking an anti-tumour response is not fully understood. Methods: The present study examined whether a single dose of 5-ADC enhances the cytotoxic and anti-tumour immune effect of low dose PDT with verteporfin as the photosensitiser in a TNBC orthotopic syngeneic murine model, using the triple negative murine mammary tumour cell line 4T1. Histopathology analysis, digital pathology and immunohistochemistry of treated tumours and distant sites were assessed. Flow cytometry of splenic and breast tissue was used to identify T cell populations. Bioinformatics were used to identify tumour immune microenvironments related to TNBC patients. Results: Functional experiments showed that PDT was most effective when used in combination with 5-ADC to optimize its efficacy. 5-ADC/PDT combination therapy elicited a synergistic effect in vitro and was significantly more cytotoxic than monotherapies on 4T1 tumour cells. For tumour therapy, all types of treatments demonstrated histopathologically defined margins of necrosis, increased T cell expression in the spleen with absence of metastases or distant tissue destruction. Flow cytometry and digital pathology results showed significant increases in CD8 expressing cells with all treatments, whereas only the 5-ADC/PDT combination therapy showed increase in CD4 expression. Bioinformatics analysis of in silico publicly available TNBC data identified BCL3 and BCL2 as well as the following anti-tumour immune response biomarkers as significantly altered in TNBC compared to other breast cancer subtypes: GZMA, PRF1, CXCL1, CCL2, CCL4, and CCL5. Interestingly, molecular biomarker assays showed increase in anti-tumour response genes after treatment. The results showed concomitant increase in BCL3, with decrease in BCL2 expression in TNBC treatment. In addition, the treatments showed decrease in PRF1, CCL2, CCL4, and CCL5 genes with 5-ADC and 5-ADC/PDT treatment in both spleen and breast tissue, with the latter showing the most decrease. Discussion: To our knowledge, this is the first study that shows which of the innate and adaptive immune biomarkers are activated during PDT related treatment of the TNBC 4T1 mouse models. The results also indicate that some of the immune response biomarkers can be used to monitor the effectiveness of PDT treatment in TNBC murine model warranting further investigation in human subjects.

Digital Tracking of Patients Undergoing Radical Cystectomy for Bladder Cancer: Daily Step Counts Before and After Surgery Within the iROC Randomised Controlled Trial.

BACKGROUND: Efforts to improve recovery after radical cystectomy (RC) are needed. OBJECTIVE: To investigate wrist-worn wearable activity trackers in RC participants. DESIGN, SETTING, AND PARTICIPANTS: An observational cohort study was conducted within the iROC randomised trial. INTERVENTION: Patients undergoing RC at nine cancer centres wore wrist-based trackers for 7 days (d) at intervals before and after surgery. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Step counts were compared with participant and operative features, and recovery outcomes. RESULTS AND LIMITATIONS: Of 308 participants, 284 (92.2%) returned digital activity data at baseline (median 17 d [interquartile range: 8-32] before RC), and postoperatively (5 [5-6] d) and at weeks 5 (43 [38-43] d), 12 (94 [87-106] d), and 26 (192 [181-205] d) after RC. Compliance was affected by the time from surgery and a coronavirus disease 2019 pandemic lockdown (return rates fell to 0-7%, chi-square p < 0.001). Step counts dropped after surgery (mean of 28% of baseline), before recovering at 5 weeks (wk) (71% of baseline) and 12 wk (95% of baseline; all analysis of variance [ANOVA] p < 0.001). Baseline step counts were not associated with postoperative recovery or death. Patients with extended hospital stays had reduced postoperative step counts, with a difference of 2.2 d (95% confidence interval: 0.856-3.482 d) between the lowest third and highest two-third tertiles (linear regression analysis; p < 0.001). Additionally, they spent less time out of the hospital within 90 d of RC (80.3 vs 74.3 d, p = 0.013). Lower step counts at 5, 12, and 26 wk were seen in those seeking medical help and needing readmission (ANOVA p ≤ 0.002). CONCLUSIONS: Baseline step counts were not associated with recovery. Lower postoperative step counts were associated with longer length of stay at the hospital and postdischarge readmissions. Studies are required to determine whether low step counts can identify patients at a risk of developing complications. PATIENT SUMMARY: Postoperative step counts appear to be a promising tool to identify patients in the community needing medical help or readmission. More work is needed to understand which measures are most useful and how best to collect these.

WAFER trial: a study protocol for a feasibility randomised controlled trial comparing wide-awake local anaesthesia no tourniquet (WALANT) to general and regional anaesthesia with tourniquet for flexor tendon repair.

INTRODUCTION: Flexor tendons are traditionally repaired under either general anaesthesia (GA) or regional anaesthesia (RA), allowing for the use of an arm tourniquet to minimise blood loss and establish a bloodless surgical field. However, the use of tourniquets exposes the patient to certain risks, including skin, muscle and nerve injuries. A recent advancement in anaesthesia delivery involves the use of a wide-awake approach where no sedation nor tourniquets are used (wide-awake local anaesthesia no tourniquet (WALANT)). WALANT uses local anaesthetic with epinephrine to provide pain relief and vasoconstriction, reducing operative bleeding. Several studies revealed potential benefits for WALANT compared with GA or RA. However, there remains a paucity of high-quality evidence to support the use of WALANT. As a result of this uncertainty, the clinical practice varies considerably. We aim to evaluate the feasibility of WALANT as an alternative to GA and RA in patients undergoing surgical repair of flexor tendon injuries. This involves addressing factors such as clinician and patient support for a trial, clinical equipoise, trial recruitment and dropout and the most relevant outcomes measures for a future definitive trial. METHODS AND ANALYSIS: WAFER is a multicentre, single-blinded, parallel group, randomised controlled trial (RCT) to assess the feasibility of WALANT versus RA and GA. The target population is patients with acute traumatic flexor tendon injuries, across 3 major hand surgery units in England involving a total of 60 participants. Outcome assessors will be blinded. The primary outcome will be the ability to recruit patients into the trial, while secondary outcomes include difference in functional outcome, patient-reported outcome measures, health-related quality of life, cost-effectiveness and complication rates. ETHICS AND DISSEMINATION: Ethical approval was obtained from the London-City and East Research Ethics Committee (22/PR/1197). Findings will be disseminated through peer-reviewed publication, conferences, patient information websites and social media networks. TRIAL REGISTRATION NUMBER: ISRCTN identifier: 15052559.

Cost-Effectiveness of Robot-Assisted Radical Cystectomy vs Open Radical Cystectomy for Patients With Bladder Cancer.

Importance: The value to payers of robot-assisted radical cystectomy with intracorporeal urinary diversion (iRARC) when compared with open radical cystectomy (ORC) for patients with bladder cancer is unclear. Objectives: To compare the cost-effectiveness of iRARC with that of ORC. Design, Setting, and Participants: This economic evaluation used individual patient data from a randomized clinical trial at 9 surgical centers in the United Kingdom. Patients with nonmetastatic bladder cancer were recruited from March 20, 2017, to January 29, 2020. The analysis used a health service perspective and a 90-day time horizon, with supplementary analyses exploring patient benefits up to 1 year. Deterministic and probabilistic sensitivity analyses were undertaken. Data were analyzed from January 13, 2022, to March 10, 2023. Interventions: Patients were randomized to receive either iRARC (n = 169) or ORC (n = 169). Main Outcomes and Measures: Costs of surgery were calculated using surgery timings and equipment costs, with other hospital data based on counts of activity. Quality-adjusted life-years were calculated from European Quality of Life 5-Dimension 5-Level instrument responses. Prespecified subgroup analyses were undertaken based on patient characteristics and type of diversion. Results: A total of 305 patients with available outcome data were included in the analysis, with a mean (SD) age of 68.3 (8.1) years, and of whom 241 (79.0%) were men. Robot-assisted radical cystectomy was associated with statistically significant reductions in admissions to intensive therapy (6.35% [95% CI, 0.42%-12.28%]), and readmissions to hospital (14.56% [95% CI, 5.00%-24.11%]), but increases in theater time (31.35 [95% CI, 13.67-49.02] minutes). The additional cost of iRARC per patient was £1124 (95% CI, -£576 to £2824 [US $1622 (95% CI, -$831 to $4075)]) with an associated gain in quality-adjusted life-years of 0.01124 (95% CI, 0.00391-0.01857). The incremental cost-effectiveness ratio was £100 008 (US $144 312) per quality-adjusted life-year gained. Robot-assisted radical cystectomy had a much higher probability of being cost-effective for subgroups defined by age, tumor stage, and performance status. Conclusions and Relevance: In this economic evaluation of surgery for patients with bladder cancer, iRARC reduced short-term morbidity and some associated costs. While the resulting cost-effectiveness ratio was in excess of thresholds used by many publicly funded health systems, patient subgroups were identified for which iRARC had a high probability of being cost-effective. Trial Registration: ClinicalTrials.gov Identifier: NCT03049410.

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.

Analysis of Clinical Trials and Review of Recent Advances in Therapy Decisions for Locally Advanced Prostate Cancer.

Despite the implementation of screening and early detection in many countries, the prostate cancer mortality rate remains high, particularly when the cancer is locally advanced. Targeted therapies with high efficacy and minimal harms should be particularly beneficial in this group, and several new approaches show promise. This article briefly analyses relevant clinical studies listed on ClinicalTrials.gov, combined with a short literature review that considers new therapeutic approaches that can be investigated in future clinical trials. Therapies using gold nanoparticles are of special interest in low-resource settings as they can localize and enhance the cancer-cell killing potential of X-rays using equipment that is already widely available.

Microorganisms and Breast Cancer: An In-Depth Analysis of Clinical Studies.

Breast cancer is a multifactorial disease that affects millions of women worldwide. Recent work has shown intriguing connections between microorganisms and breast cancer, which might have implications for prevention and treatment. This article analyzed 117 relevant breast cancer clinical studies listed on ClinicalTrials.gov selected using a bespoke set of 38 search terms focused on bacteria, viruses, and fungi. This was supplemented with 20 studies found from a search of PubMed. The resulting 137 studies were described by their characteristics such as geographic distribution, interventions used, start date and status, etc. The studies were then collated into thematic groups for a descriptive analysis to identify knowledge gaps and emerging trends.

NeuroSAFE PROOF: study protocol for a single-blinded, IDEAL stage 3, multi-centre, randomised controlled trial of NeuroSAFE robotic-assisted radical prostatectomy versus standard robotic-assisted radical prostatectomy in men with localized prostate cancer.

BACKGROUND: Robotic radical prostatectomy (RARP) is a first-line curative treatment option for localized prostate cancer. Postoperative erectile dysfunction and urinary incontinence are common associated adverse side effects that can negatively impact patients' quality of life. Preserving the lateral neurovascular bundles (NS) during RARP improves functional outcomes. However, selecting men for NS may be difficult when there is concern about incurring in positive surgical margin (PSM) which in turn risks adverse oncological outcomes. The NeuroSAFE technique (intra-operative frozen section examination of the neurovascular structure adjacent prostate margin) can provide real-time pathological consult to promote optimal NS whilst avoiding PSM. METHODS: NeuroSAFE PROOF is a single-blinded, multi-centre, randomised controlled trial (RCT) in which men are randomly allocated 1:1 to either NeuroSAFE RARP or standard RARP. Men electing for RARP as primary treatment, who are continent and have good baseline erectile function (EF), defined by International Index of Erectile Function (IIEF-5) score > 21, are eligible. NS in the intervention arm is guided by the NeuroSAFE technique. NS in the standard arm is based on standard of care, i.e. a pre-operative image-based planning meeting, patient-specific clinical information, and digital rectal examination. The primary outcome is assessment of EF at 12 months. The primary endpoint is the proportion of men who achieve IIEF-5 score ≥ 21. A sample size of 404 was calculated to give a power of 90% to detect a difference of 14% between groups based on a feasibility study. Oncological outcomes are continuously monitored by an independent Data Monitoring Committee. Key secondary outcomes include urinary continence at 3 months assessed by the international consultation on incontinence questionnaire, rate of biochemical recurrence, EF recovery at 24 months, and difference in quality of life. DISCUSSION: NeuroSAFE PROOF is the first RCT of intra-operative frozen section during radical prostatectomy in the world. It is properly powered to evaluate a difference in the recovery of EF for men undergoing RARP assessed by patient-reported outcome measures. It will provide evidence to guide the use of the NeuroSAFE technique around the world. TRIAL REGISTRATION: NCT03317990 (23 October 2017). Regional Ethics Committee; reference 17/LO/1978.

Effect of Robot-Assisted Radical Cystectomy With Intracorporeal Urinary Diversion vs Open Radical Cystectomy on 90-Day Morbidity and Mortality Among Patients With Bladder Cancer: A Randomized Clinical Trial.

Importance: Robot-assisted radical cystectomy is being performed with increasing frequency, but it is unclear whether total intracorporeal surgery improves recovery compared with open radical cystectomy for bladder cancer. Objectives: To compare recovery and morbidity after robot-assisted radical cystectomy with intracorporeal reconstruction vs open radical cystectomy. Design, Setting, and Participants: Randomized clinical trial of patients with nonmetastatic bladder cancer recruited at 9 sites in the UK, from March 2017-March 2020. Follow-up was conducted at 90 days, 6 months, and 12 months, with final follow-up on September 23, 2021. Interventions: Participants were randomized to receive robot-assisted radical cystectomy with intracorporeal reconstruction (n = 169) or open radical cystectomy (n = 169). Main Outcomes and Measures: The primary outcome was the number of days alive and out of the hospital within 90 days of surgery. There were 20 secondary outcomes, including complications, quality of life, disability, stamina, activity levels, and survival. Analyses were adjusted for the type of diversion and center. Results: Among 338 randomized participants, 317 underwent radical cystectomy (mean age, 69 years; 67 women [21%]; 107 [34%] received neoadjuvant chemotherapy; 282 [89%] underwent ileal conduit reconstruction); the primary outcome was analyzed in 305 (96%). The median number of days alive and out of the hospital within 90 days of surgery was 82 (IQR, 76-84) for patients undergoing robotic surgery vs 80 (IQR, 72-83) for open surgery (adjusted difference, 2.2 days [95% CI, 0.50-3.85]; P = .01). Thromboembolic complications (1.9% vs 8.3%; difference, -6.5% [95% CI, -11.4% to -1.4%]) and wound complications (5.6% vs 16.0%; difference, -11.7% [95% CI, -18.6% to -4.6%]) were less common with robotic surgery than open surgery. Participants undergoing open surgery reported worse quality of life vs robotic surgery at 5 weeks (difference in mean European Quality of Life 5-Dimension, 5-Level instrument scores, -0.07 [95% CI, -0.11 to -0.03]; P = .003) and greater disability at 5 weeks (difference in World Health Organization Disability Assessment Schedule 2.0 scores, 0.48 [95% CI, 0.15-0.73]; P = .003) and at 12 weeks (difference in WHODAS 2.0 scores, 0.38 [95% CI, 0.09-0.68]; P = .01); the differences were not significant after 12 weeks. There were no statistically significant differences in cancer recurrence (29/161 [18%] vs 25/156 [16%] after robotic and open surgery, respectively) and overall mortality (23/161 [14.3%] vs 23/156 [14.7%]), respectively) at median follow-up of 18.4 months (IQR, 12.8-21.1). Conclusions and Relevance: Among patients with nonmetastatic bladder cancer undergoing radical cystectomy, treatment with robot-assisted radical cystectomy with intracorporeal urinary diversion vs open radical cystectomy resulted in a statistically significant increase in days alive and out of the hospital over 90 days. However, the clinical importance of these findings remains uncertain. Trial Registration: ISRCTN Identifier: ISRCTN13680280; ClinicalTrials.gov Identifier: NCT03049410.

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.