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Objectives To report on the methods, peri-operative outcomes and histopathological concordance between frozen and final section from the NeuroSAFE PROOF feasibility study (NCT03317990). Patients and methods Between May 2018 and March 2019, 49 patients at two UK centres underwent robot-assisted radical prostatectomy (RARP). Twenty-five patient were randomized to NeuroSAFE RARP (intervention arm) and 24 to standard RARP (control arm). Frozen section was compared to final paraffin section margin assessment in the 25 patients in the NeuroSAFE arm. Operation timings and complications were collected prospectively in both arms. Results Fifty neurovascular bundles (NVBs) from 25 patients in the NeuroSAFE arm were analysed. When analysed by each pathological section (n = 250, average five per side), we noted a sensitivity of 100%, a specificity of 99.2%, and an area under the curve (AUC) of 0.994 (95% confidence interval [CI] 0.985 to 1; P ≤0.001). On an NVB basis (n = 50), sensitivity was 100%, specificity was 92.7%, and the AUC was 0.963 (95% CI 0.914 to 1; P ≤0.001). NeuroSAFE RARP lasted a mean of 3 h 16 min (knife to skin to off table, 95% CI 3 h 2 min-3 h 30 min) compared to 2 h 4 min (95% CI 2 h 2 min-2 h 25 min; P ≤0.001) for standard RARP. There was no morbidity associated with the additional length of operating time on in the NeuroSAFE arm. Conclusion This feasibility study demonstrates the safety, reproducibility and excellent histopathological concordance of the NeuroSAFE technique in the NeuroSAFE PROOF trial. Although the technique increases the duration of RARP, this does not cause short-term harm. Confirmation of feasibility has led to the opening of the fully powered NeuroSAFE PROOF randomized controlled trial, which is currently under way at four sites in the UK.

OBJECTIVE: To investigate whether patients with Gleason 3 + 4 cancer on transrectal biopsy are upgraded after undergoing transperineal magnetic resonance imaging (MRI)-targeted biopsy and whether this has implications for current clinical practice. PATIENTS AND METHODS: In this retrospective analysis we examined 107 consecutive patients presenting at a single tertiary referral centre (July 2012 to July 2016) with prostate cancer of Gleason score 3 + 4 on transrectal ultrasonography (TRUS)-guided systematic non-targeted biopsy who then underwent a multiparametric MRI followed by MRI-targeted transperineal prostate biopsy for accurate risk stratification and localization. RESULTS: The patients' mean (sd) age was 67.0 (8.0) years, and they had a median (interquartile range) PSA concentration of 6.2 (4.7-9.6) ng/mL. Of the 107 patients, 84 (78.5%) had Gleason 3 + 4 on both transrectal systematic biopsy and transperineal MRI-targeted biopsy. Nineteen patients (17.8%) were upgraded to Gleason 4 + 3, three patients (3.0%) to Gleason 4 + 4 and one patient (1.0%) to Gleason 4 + 5. These differences were significant (P = 0.0006). Likewise, 23/107 patients (22%) had higher-risk disease based on their targeted biopsies. CONCLUSION: The use of targeted biopsy in men with impalpable cancer, ultimately upgraded one in five patients from favourable-intermediate- to unfavourable-intermediate-risk disease or worse. This has significant clinical implications for men considering active surveillance or radical treatment. Our risk calculators must now be validated using these data from targeted biopsy as the technique becomes widely adopted.

Objectives To evaluate the optimal treatment conditions and effects of TOOKAD® Soluble vascular-targeted photodynamic (VTP) therapy in patients with localised prostate cancer. To evaluate the safety and quality of life after TOOKAD® Soluble VTP treatment in patients with localised prostate cancer. Patients and Methods Men (aged >18 years) diagnosed with localised prostate cancer, who were suitable for active surveillance, were invited to take part in the study. Patients who had received prior or current treatment for their cancer were excluded. There were two parts to the study: in part one, patients were assigned to one of two treatment groups based on the size of their prostates (patients with prostate size 80% of patients treated with this regimen having a negative biopsy at 6 months. Overall, the treatment was well tolerated and exhibited early signs of efficacy for minimally invasive focal treatment of localised prostate cancer.

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.

Study Type – Diagnosis (exploratory cohort) Level of Evidence 2b OBJECTIVE To investigate the use of magnetic resonance imaging (MRI) of the penis during an episode of priapism and assess the viability of the corpus cavernosum (CC) smooth muscle, as prolonged ischaemic priapism is associated with a high rate of long-term erectile dysfunction (ED), and the viability of CC smooth muscle influences the subsequent management in ischaemic priapism. PATIENTS AND METHODS The study was set in a single centre based in a large university teaching hospital. We investigated the correlation of T2-weighted gadolinium- enhanced MRI with the histology from CC biopsies in the same patients. In all, 38 patients (mean age 42 years) presenting with priapism over a 3-year period had MRI of the penis. The scans were reported by two dedicated uro-radiologists who graded the MR images as showing viable or nonviable erectile tissue. One pathologist assessed the CC biopsies for necrosis. The findings were then correlated. Where no biopsies were taken a clinical follow-up was used to assess erectile function. RESULTS In 23 patients undergoing both a CC biopsy and MRI, the sensitivity of MRI in predicting nonviable smooth muscle was 100%. In a further 10 patients MRI showed nonviable CC smooth muscle, but no biopsy was taken in these patients; on clinical follow-up all of these patients subsequently developed ED. In a further five patients the imaging showed viable smooth muscle and these patients subsequently maintained erectile function on clinical follow up. CONCLUSIONS Penile MRI provides an accurate imaging method to assess smooth muscle viability in patients presenting with priapism.

Objective To determine the optimal drug and light dose for prostate ablation using WST11 (TOOKAD® Soluble) for vascular-targeted photodynamic (VTP) therapy in men with low-risk prostate cancer. Patients and Methods In all, 42 men with low-risk prostate cancer were enrolled in the study but two who underwent anaesthesia for the procedure did not receive the drug or light dose. Thus, 40 men received a single dose of 2, 4 or 6 mg/kg WST11 activated by 200 J/cm light at 753 nm. WST11 was given as a 10-min intravenous infusion. The light dose was delivered using cylindrical diffusing fibres within hollow plastic needles positioned in the prostate using transrectal ultrasonography (TRUS) guidance and a brachytherapy template. Magnetic resonance imaging (MRI) was used to assess treatment effect at 7 days, with assessment of urinary function (International Prostate Symptom Score [IPSS]), sexual function (International Index of Erectile Function [IIEF]) and adverse events at 7 days, 1, 3 and 6 months after VTP. TRUS-guided biopsies were taken at 6 months. Results In all, 39 of the 40 treated men completed the follow-up. The Day-7 MRI showed maximal treatment effect (95% of the planned treatment volume) in men who had a WST11 dose of 4 mg/kg, light dose of 200 J/cm and light density index (LDI) of >1. In the 12 men treated with these parameters, the negative biopsy rate was 10/12 (83%) at 6 months, compared with 10/26 (45%) for the men who had either a different drug dose (10 men) or an LDI of 1 resulted in treatment effect in 95% of the planned treatment volume and a negative biopsy rate at 6 months of 10/12 men (83%).

OBJECTIVE To report on the high rectal fistula rate associated with salvage high-intensity focused ultrasound (HIFU) after the failure of combined brachytherapy and external beam radiotherapy (EBRT) for prostate cancer; salvage ablative therapy for prostate cancer is indicated when there is local recurrence after RT, brachytherapy or their combination. PATIENTS AND METHODS We retrospectively reviewed all men with prostate cancer treated with HIFU between 1 March 2005 and 31 May 2007, and identified five men treated after the failure of both brachytherapy and EBRT for localized prostate cancer. RESULTS Three of the five men had iodine-seed implantation brachytherapy combined with EBRT as primary treatment, one had high-dose rate brachytherapy combined with EBRT and one had salvage iodine-seed brachytherapy for failed EBRT. Three of the five patients developed a recto-urethral fistula after HIFU. CONCLUSIONS The high rate of recto-urethral fistula formation in this group might reflect an impaired blood supply or HIFU-associated near-field heating of the rectal wall. Tissue viability and healing might affect this group regardless of the salvage method. Careful patient selection and avoidance of rectal diagnostic biopsies might minimize the risk. Emerging ablative therapies regarded as less invasive than traditional therapies must be used with caution.

To evaluate the optimal treatment conditions and effects of TOOKAD(®) Soluble vascular-targeted photodynamic (VTP) therapy in patients with localised prostate cancer. To evaluate the safety and quality of life after TOOKAD(®) Soluble VTP treatment in patients with localised prostate cancer.Men (aged18 years) diagnosed with localised prostate cancer, who were suitable for active surveillance, were invited to take part in the study. Patients who had received prior or current treatment for their cancer were excluded. There were two parts to the study: in part one, patients were assigned to one of two treatment groups based on the size of their prostates (patients with prostate size60 mL would receive 4 mg/kg TOOKAD(®) Soluble and patients with prostate size ≥60 mL would receive 6 mg/kg TOOKAD(®) Soluble both activated with 200 J/cm light). In part two, patients were assigned to one of two treatment groups based on predefined criteria and received either 4 or 6 mg/kg TOOKAD(®) Soluble and 200 or 300 J/cm light. VTP was conducted under general anaesthesia using TOOKAD(®) Soluble administered intravenously and activated by light-diffusing fibres within the prostate via the perineum. Follow-up was conducted for 6 months. Magnetic resonance imaging (MRI) carried out at 1 week after VTP and transrectal prostate biopsy at 6 months were the key endpoints. Adverse event (AE) recording and patient-reported outcome measures were collected.In all, 86 patients were enrolled in the study and 85 patients received treatment. Of the 85 treated patients, one patient discontinued (due to withdrawal of consent). At 6 months, 61/83 (74%) patients who underwent prostate biopsy had histopathology that was negative for prostate cancer (95% confidence interval (CI) 62.7-82.6%). Considering patients who received 4 mg/kg TOOKAD(®) Soluble and 200 J/cm light (unilateral), which are considered optimal treatment parameters, 38/46 (83%) patients had histopathology from the biopsies that was negative for prostate cancer at 6 months (95% CI 68.6-92.2%; P0.001). The mean percentage of necrosis of the targeted prostate tissue at 7 days after VTP was 78% overall (83 patients) with extraprostatic necrosis reported in 76% (63/83) of patients. Considering patients who received 4 mg/kg TOOKAD(®) Soluble and 200 J/cm light (unilateral), the mean 7-day necrosis percentage was 88% (46 patients) with extraprostatic necrosis reported in 72% (33/46) of patients. All occurrences of extraprostatic necrosis were considered clinically acceptable and none were associated with any clinical sequelae. The mean percentage prostate necrosis at 7 days was statistically significantly higher (P0.001) in patients treated with a therapeutic light density index (LDI) of ≥1 than those treated with a LDI of1. The percentage of patients with negative biopsies at 6 months was also higher in patients treated with a therapeutic LDI of ≥1 than those treated with a LDI of1 (78.6% and 63.0%, respectively). In all, 87% (75/86) of patients reported at least one treatment-emergent AE during the study. Most AEs were mild or moderate in intensity and considered related to the technical procedures of the study. No treated patients had hypotension or discontinued due to AEs. Eight patients (9.3%) had serious AEs; none resulted in discontinuation from the study.Biopsy data, post-treatment dynamic contrast-enhancement MRI at 1 week after VTP and analysis of the safety data have shown that 4 mg/kg TOOKAD(®) Soluble and 200 J/cm light are the optimal treatment conditions for the VTP procedure resulting in80% of patients treated with this regimen having a negative biopsy at 6 months. Overall, the treatment was well tolerated and exhibited early signs of efficacy for minimally invasive focal treatment of localised prostate cancer.

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

OBJECTIVES To investigate the use of minimally invasive high-intensity focused ultrasound (HIFU) as a salvage therapy in men with localized prostate cancer recurrence following external beam radiotherapy (EBRT). PATIENTS AND METHODS A review of 31 cases treated using the Sonablate® 500 HIFU device, between 1 February 2005 and 15 May 2007, was carried out. All men had presumed organ-confined, histologically confirmed recurrent prostate adenocarcinoma following EBRT. RESULTS The mean (range) age was 65 (57–80) years with a mean preoperative PSA level of 7.73 (0.20–20) ng/mL. The patients were followed for a mean (range) of 7.4 (3–24) months. Side-effects included stricture or intervention for necrotic tissue in 11 of the 31 patients (36%), urinary tract infection or dysuria syndrome in eight (26%), and urinary incontinence in two (7%). Recto-urethral fistula occurred in two men, although one was due to patient movement due to inadequate anaesthesia, so the ‘true’ rate is 3%. Half of the patients had PSA levels of