Evaluating the Effects of Frozen Section Technology on Oncological and Functional Outcomes at Radical Prostatectomy.

NCT03317990 | Active Not Recruiting Results DMC

• 2 other identifiers: 22026217/0443
• Study Type: interventional
• Target: 407
• Locations: 1 country
• Sites: 5

Brief Summary

In summary this trial will test whether this new surgical technique can be used to make surgery safer and more effective whilst allowing improved quality of life for patients having surgery for prostate cancer. If the technique is proven effective the investigators will use the experience gained to promote its use throughout the NHS through training courses and publication and dissemination of the resultant data. Staff from centres participating in this trial will be fully trained in the NeuroSAFE technique. A patient and public involvement afternoon was held for participants of the NeuroSAFE PROOF feasibility study, family members, men with prostate cancer, and staff members at UCLH. The event was supported by the charity Orchid Cancer appeal. The high levels of attendance was demonstrative of the support within our patient group for the work of this trial. The trial team listened to the comments made by participants and members of the public and have made some changes to the design of our trial as a result of this feedback.

Conditions

Prostate Cancer

Keywords

Prostate Cancer; Nerve sparing; NeuroSAFE; Frozen section

Outcome Measures

Primary Outcomes (1)

• Erectile Function

  Comparison of the erectile function at 12-months according to allocated treatment arm (i.e. NeuroSAFE RARP \[intervention\] vs. standard RARP \[control\]). Erectile function is measured using the IIEF-5 questionnaire Measure Description: The International Index of Erectile Function-5 (IIEF-5) measures erectile dysfunction severity. Total scores range from 5 to 25, calculated by summing 5 items. Higher scores indicate better erectile function. Severity categories: 22-25 = no erectile disfunction, 17-21 = mild, 12-16 = mild to moderate, 8-11 = moderate, 5-7 = severe. No subscales are used; the total score is the sum of all items.

  1 year

Secondary Outcomes (7)

• Functional Outcome - Urinary Continence

  3 months

• Functional Outcome - Urinary Continence at 6 Months

  6 months

• Oncological Outcome

  12 months after surgery

• Quality of Life - EQ-5D-5L

  12 months and 24 months

• Quality of Life - EQ-5D-5L Score

  12 months and 24 months

Study Arms (2)

NeuroSAFE procedure

EXPERIMENTAL

These patients will undergo robotic radical prostatectomy with bilateral nerve spare.The pathologist will remove the pre-painted surface of the gland (which had been in contact with the neurovascular bundles) using a sharp blade.The tissue sample will be snap frozen and embedded in OCT.Using a cryostat, 10 micron thick slices will be placed on slides.The entire length of the area of interest will be sampled in this way generating ≈10 frozen sections per side.The slides will be stained with H\&E and will be examined by a consultant pathologist.As soon as examination is complete the pathologist will telephone the operating surgeon to give the result.Presence of cancer cells at the margin of resection constitutes a positive margin and the neurovascular bundle on that side will be resected if the PSM is present in more than one slice on the same side or for a distance of 3 or more mm.

Procedure: NeuroSAFE procedure

Control

ACTIVE COMPARATOR

These patients will undergo robotic radical prostatectomy with a nerve sparing procedure based on surgical planning performed by a consultant radiologist. The mp-MRI will be reviewed by a consultant radiologist along with the details of the prostate biopsy and DRE a decision to perform unilateral, bilateral or non-nerve sparing will be established and recorded in the clinical record form (CRF) for each patient.

Procedure: Standard RARP

Interventions

NeuroSAFE procedure PROCEDURE

When the prostate is removed from within the patient as it is disconnected from its attachments. The specimen will then be painted (right=blue, left =black) by the operating surgeon and delivered expediently to the pathologist who will perform frozen section analysis of the painted areas. The pathologist will remove the pre-painted surface of the gland (which had been in contact with the neurovascular bundles) using a sharp blade. The tissue sample will be snap frozen and embedded in OCT. If a significant positive margin (on more than one section from one side or in a single section but greater than or equal to 3mm) is reported by the pathologist, the entire neurovascular bundle on the affected side will be removed and sent for formal pathological examination.

Also known as: NeuroSAFE RARP

NeuroSAFE procedure

Standard RARP PROCEDURE

Patients will undergo the standard intervention - RARP without NeuroSAFE Frozen section analysis

Control

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men opting to undergo RARP for organ confined prostate cancer.
• Potent men (IIEF 22-25 not using PDE5i or other medications or vacuum pump)
• Men who are continent of urine (no self-reported urinary incontinence)
• Has given written informed consent
• Ability to read English sufficiently to answer questionnaires and understand PIS

You may not qualify if:

• Unable to undergo robotic prostatectomy
• Known urinary incontinence
• Previous treatment for prostate cancer
• Previous/current hormone treatment for prostate cancer
• Nerve sparing deemed futile due to locally advanced disease by surgeon and radiologist

Sponsors & Collaborators

• University College, London: lead
• North Bristol NHS Trust: collaborator
• Sheffield Teaching Hospitals NHS Foundation Trust: collaborator
• University College London Hospitals: collaborator
• NHS Greater Glasgow and Clyde: collaborator

Study Sites (5)

North Bristol NHS Trust

Bristol, BS10 5NB, United Kingdom

Location

NHS Greater Glasgow & Clyde

Glasgow, United Kingdom

Location

University College London Hospital

London, NW1 2BU, United Kingdom

Location

Nottingham University Hospitals

Nottingham, United Kingdom

Location

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, S10 2JF, United Kingdom

Location

Related Publications (8)

• https://doi.org/10.6084/m9.figshare.27054979.v1

  BACKGROUND

• Beyer B, Schlomm T, Tennstedt P, Boehm K, Adam M, Schiffmann J, Sauter G, Wittmer C, Steuber T, Graefen M, Huland H, Haese A. A feasible and time-efficient adaptation of NeuroSAFE for da Vinci robot-assisted radical prostatectomy. Eur Urol. 2014 Jul;66(1):138-44. doi: 10.1016/j.eururo.2013.12.014. Epub 2013 Dec 24.

  PMID: 24411279 BACKGROUND

• Vasdev N, Agarwal S, Rai BP, Soosainathan A, Shaw G, Chang S, Prasad V, Mohan-S G, Adshead JM. Intraoperative Frozen Section of the Prostate Reduces the Risk of Positive Margin Whilst Ensuring Nerve Sparing in Patients with Intermediate and High-Risk Prostate Cancer Undergoing Robotic Radical Prostatectomy: First Reported UK Series. Curr Urol. 2016 May;9(2):93-103. doi: 10.1159/000442860. Epub 2016 May 20.

  PMID: 27390582 BACKGROUND

• Dinneen E, Almeida-Magana R, Al-Hammouri T, Pan S, Leurent B, Haider A, Freeman A, Roberts N, Brew-Graves C, Grierson J, Clow R, Williams N, Aning J, Walton T, Persad R, Oakley N, Ahmad I, Dutto L, Briggs T, Allen C, Tandogdu Z, Adshead J, Oxley J, Kelly J, Shaw G; NeuroSAFE PROOF Investigators. Effect of NeuroSAFE-guided RARP versus standard RARP on erectile function and urinary continence in patients with localised prostate cancer (NeuroSAFE PROOF): a multicentre, patient-blinded, randomised, controlled phase 3 trial. Lancet Oncol. 2025 Apr;26(4):447-458. doi: 10.1016/S1470-2045(25)00091-9. Epub 2025 Mar 24.

  PMID: 40147459 DERIVED

• Dinneen E, Grierson J, Almeida-Magana R, Clow R, Haider A, Allen C, Heffernan-Ho D, Freeman A, Briggs T, Nathan S, Mallett S, Brew-Graves C, Muirhead N, Williams NR, Pizzo E, Persad R, Aning J, Johnson L, Oxley J, Oakley N, Morgan S, Tahir F, Ahmad I, Dutto L, Salmond JM, Kelkar A, Kelly J, Shaw G. 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. Trials. 2022 Jul 22;23(1):584. doi: 10.1186/s13063-022-06421-7.

  PMID: 35869497 DERIVED

• Almeida-Magana R, Maroof H, Grierson J, Clow R, Dinneen E, Al-Hammouri T, Muirhead N, Brew-Graves C, Kelly J, Shaw G. E-Consent-a guide to maintain recruitment in clinical trials during the COVID-19 pandemic. Trials. 2022 May 12;23(1):388. doi: 10.1186/s13063-022-06333-6.

  PMID: 35550639 DERIVED

• Dinneen E, Haider A, Grierson J, Freeman A, Oxley J, Briggs T, Nathan S, Williams NR, Brew-Graves C, Persad R, Aning J, Jameson C, Ratynska M, Ben-Salha I, Ball R, Clow R, Allen C, Heffernan-Ho D, Kelly J, Shaw G. NeuroSAFE frozen section during robot-assisted radical prostatectomy: peri-operative and histopathological outcomes from the NeuroSAFE PROOF feasibility randomized controlled trial. BJU Int. 2021 Jun;127(6):676-686. doi: 10.1111/bju.15256. Epub 2021 Mar 29.

  PMID: 32985121 DERIVED

• Dinneen E, Haider A, Allen C, Freeman A, Briggs T, Nathan S, Brew-Graves C, Grierson J, Williams NR, Persad R, Oakley N, Adshead JM, Huland H, Haese A, Shaw G. NeuroSAFE robot-assisted laparoscopic prostatectomy versus standard robot-assisted laparoscopic prostatectomy for men with localised prostate cancer (NeuroSAFE PROOF): protocol for a randomised controlled feasibility study. BMJ Open. 2019 Jun 11;9(6):e028132. doi: 10.1136/bmjopen-2018-028132.

  PMID: 31189680 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Limitations and Caveats

Several limitations are to be mentioned. First, oncological outcomes are limited to 12 months, most procedures were performed at one centre, clinical research team members who conducted the follow-up assessments were aware of treatment allocation. Definition and analysis methods for the primary outcome was changed after the study commenced. Results analysis is ongoing; results on quality of life, health economic analysis, and 2 year functional and oncological outcomes will be published in 2026.

Results Point of Contact

• Title: Professor Greg Shaw
• Organization: University College London

ncita.neurosafe@ucl.ac.uk

+44 (0)20 7679 2000

Study Officials

• Greg L Shaw, MD

  University College, London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Patients will be blinded as to whether the person has had NeuroSAFE procedure. The surgeon and pathologist cannot be blinded to this.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A single blinded, multi-centre, randomised controlled trial. Parallel group, two-arm, with 1:1 allocation ratio between nerve sparing guided by NeuroSAFE and current UK practice (guided by MRI, biopsy and clinical examination).

Study Record Dates

• First Submitted: October 5, 2017
• First Posted: October 23, 2017
• Study Start: April 9, 2018
• Primary Completion: April 30, 2024
• Study Completion (Estimated): December 1, 2027
• Last Updated: September 4, 2025
• Results First Posted: September 4, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Once primary outcome data is published in the final manuscript
• Access Criteria: A limited, pseudonymised dataset for the primary outcomes that underlie the results reported in the final manuscript along with the data dictionary will be available to be shared. All data (pseudonymised) will remain under the custodianship of the trial management group (TMG). Requests for data are submitted to the committee via (ncita.neurosafe@ucl.ac.uk). A data access agreement will need to be signed. As the NeuroSAFE PROOF study is ongoing, we will not share the full dataset until follow-up of participants is completed and the long-term follow up final manuscript has been published.

Locations

GB (5)