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.

Retzius-sparing technique independently predicts early recovery of urinary continence after robot-assisted radical prostatectomy.

Robot-assisted radical prostatectomy (RARP) is the conventional surgical treatment option for localised prostate cancer. We investigated factors which may be associated with recovery of early urinary continence (EUC), including the use of the Retzius-sparing technique (RS-RARP). From March 2018 to December 2018, 501 consecutive patients underwent RARP at our high-volume institution. Four hundred and thirty-one patients had complete follow-up data and were included in our analyses. EUC was defined as zero pad use and social urinary continence (SUC) was defined as ≤ 1 pad/24-h period at 3 months following surgery. Patient demographics and clinical factors such as age, body mass index (BMI), neurovascular bundle (NVB) sparing, RS-RARP operative technique and operating surgeon (consultant, trainee) were recorded. Median age was 64.0 years (IQR 57.0-69.0 years) with a median BMI of 27.0 (IQR 25.0-29.9). RS-RARP accounted for 59 of the 431 (13.7%) patients. 196 (45.5%), 142 (32.9%) and 86 (20.0%) received a bilateral, unilateral and nil NVB sparing, respectively. EUC was achieved by 241 patients (55.9%) and SUC was achieved in 339 (78.7%) patients. Multivariable logistic regression analysis suggests younger age (HR 1.04, 95% CI 1.01-1.07, p = 0.014) and RS-RARP technique (HR 2.19, 95% CI 1.15-4.16, p = 0.017) were independently associated with EUC at 3 months even after adjusting for BMI, external membranous urethral length and NVB sparing. Our results suggest that RS-RARP technique is independently predictive of EUC even after accounting for confounding factors. These findings should be further validated in a prospective or randomised trial.

A Phase II, Open-label study to assess safety and management change using 68Ga-THP PSMA PET/CT in patients with high risk primary prostate cancer or biochemical recurrence after radical treatment: The PRONOUNCED study.

Objectives: To assess the safety and clinical impact of a novel, kit-based formulation of 68Ga-THP PSMA positron emission tomography/computed tomography (PET/CT) when used to guide the management of patients with prostate cancer (PCa). Methods: Patients were prospectively recruited in to one of: Group A: high-risk untreated prostate cancer; Gleason score >4+3, or PSA >20 ng/mL or clinical stage >T2c. Group B: biochemical recurrence (BCR) and eligible for salvage treatment after radical prostatectomy with two consecutive rises in prostate specific antigen (PSA) with a three month interval in between reads and final PSA >0.1 ng/mL or a PSA level >0.5 ng/mL. Group C: BCR with radical curative radiotherapy or brachytherapy at least three months prior to enrolment, and an increase in PSA level >2.0 ng/mL above the nadir level after radiotherapy or brachytherapy. Patients underwent evaluation with PET/CT 60 minutes following intravenous administration of 160±30 MBq of 68Ga-THP PSMA. Safety was assessed by means including vital signs, cardiovascular profile, serum haematology, biochemistry, urinalysis, PSA, and Adverse Events (AEs). A change in management was reported when the predefined clinical management of the patient altered as a result of 68Ga-THP PSMA PET/CT findings. Results: Forty-nine patients were evaluated with PET/CT; 20 in Group A, 21 in Group B and 8 in Group C. No patients experienced serious AEs discontinued the study due to AEs, or died during the study. Two patients had Treatment Emergent AEs attributed to 68Ga-THP-PSMA (pruritus in one patient and intravenous catheter site rash in another). Management change secondary to PET/CT occurred in 42.9% of all patients; 30% in Group A, 42.9% in Group B and 75% in Group C. Conclusion: 68Ga-THP PSMA was safe to use with no serious AE and no AE resulting in withdrawal from the study. 68Ga-THP PSMA PET/CT changed the management of patients in 42.9% of the study population, comparable to studies using other PSMA tracers. These data form the basis of a planned Phase III study of 68Ga-THP PSMA in patients with prostate cancer.

Epidermal Nevus Syndrome with Fibrous Dysplasia.

A 10-year-old girl developed epidermal nevus, shortness of limb, scoliosis, hemiatrophy with history of multiple pathological fractures. Bone biopsy revealed fibrous dysplasia. This is an extremely rare combination of epidermal nevus with fibrous dysplasia.