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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03317990
Recruitment Status : Recruiting
First Posted : October 23, 2017
Last Update Posted : August 13, 2019
North Bristol NHS Trust
Sheffield Teaching Hospitals NHS Foundation Trust
University College London Hospitals
NHS Greater Glasgow and Clyde
Information provided by (Responsible Party):
University College, London

Brief Summary:
Prostate cancer is common but can commonly be cured with surgery, however, this often leads to a loss of erections, because the nerves controlling erections run in the outer coverings of the prostate. Nerve sparing, where the outer layers of the prostate are peeled off, increases post-operative potency, but also increases the risk of cancer being left behind and the need for radiotherapy, which renders the men impotent, even if they had nerve sparing surgery. A new technique called NeuroSAFE incorporates an additional safety check designed to promote nerve sparing without compromising cancer control. During surgery, a pathologist examines the prostate near the nerves to check for exposed cancer. If cancer is found, the nerve tissue is removed so the recurrence risk is similar to when cancer cells are not exposed. The investigators eventual aim is to perform a large scale RCT comparing NeuroSAFE with current UK practice (nerve sparing based on MRI scan, biopsy results and clinical examination). This application is to fund a feasibility study to ensure that men are prepared to be randomised within an RCT, and that the technique can be taught to other UK centres, so allowing participation in the multi-centre RCT. The investigators will gather data to allow us to plan the larger study by defining the primary outcome measure and powering the study based on the size and confidence interval of observed effects. This study is needed because with evidence supporting observation of low risk small cancers, a higher proportion of men undergoing surgery have capsular involvement. The investigators do not have a reliable way to detect cancer which has spread through the capsule of the prostate in whom nerve sparing would cause a positive surgical margin. The NeuroSAFE technique addresses this need and will only be available at participating centres through this trial.

Condition or disease Intervention/treatment Phase
Prostate Cancer Procedure: NeuroSAFE procedure Not Applicable

Detailed Description:

Localised prostate cancer is usually curable with surgery. Surgery often entails side effects of permanent impotence and temporary urinary incontinence. These side effects can be minimised by protecting the nerves that run in the outer layer of the prostate (nerve sparing), however this increases the risk of exposure of the underlying tumour (a positive surgical margin-PSM) and a need for extra treatment in the form of radiotherapy. PSMs are more likely to occur if the tumour is starting to grow out of the prostate (stage pT3a) and in areas where pT3a disease is suspected nerve sparing cannot safely be performed. At University College Hospital London (UCLH) the chance of a man being potent after radical prostatectomy is dependent on the amount of nervous tissue left behind. 80% of men in whom the nervous tissue is spared on both sides of the prostate would be expected to be able to get erections adequate for penetrative sexual intercourse using phosphodiesterase inhibitors (PDE5i's, viagra or similar). UK surgeons base a decision of whether to nerve spare or not on the degree of suspicion that pathological stage (pT) 3a disease is present, estimated from the patients prostate biopsies and MRI scan as well as a thorough clinical examination.

Unfortunately, our ability to detect pT3a disease is limited. even with multiparametric magnetic resonance imaging (MRI), which is regarded as the best way to distinguish pT2 from pT3a disease resulting in uncertainty as to when nerve sparing is oncologically safe. In order to decrease this uncertainty a group from Germany have developed the NeuroSAFE technique, where after nerve sparing, a frozen section analysis of the area adjacent to the nerve spare, is performed, whilst the surgeon completes the rest of the operation, and if a PSM is detected the nerve tissue is then excised. NeuroSAFE has been shown in cohort studies to decrease PSM rate whilst promoting nerve sparing and potency. No level one data exist regarding the effectiveness of this technique.

The German centre where the technique was developed now performs the technique on all cases meaning the opportunity to evaluate the technique in the setting of an RCT has been missed. The technique is only performed routinely in one NHS centre, Lister Hospital. The current situation provides a unique opportunity to fully evaluate the benefits of this technique for NHS patients. The proposed study, NeuroSAFE PROOF, is a multicentre RCT designed to compare short term oncological and functional outcomes after robotic radical prostatectomy with nerve sparing performed according to current UK practice (based on a perceived risk of pT3a disease from prostate biopsy, MRI and examination findings) with patients who have undergone the NeuroSAFE procedure. For the feasibility phase 50 patients will be randomised 1:1. A NeuroSAFE training academy will be established.

The proposed study is to evaluate the potential benefit of a novel surgical technique for NHS patients before the procedure is taken up as it has been elsewhere and the opportunity to randomise/evaluate is lost.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Feasibility study. Parallel group, two-arm, randomised trial with 1:1 allocation ratio between nerve sparing guided by NeuroSAFE and current UK practice (guided by MRI, biopsy and clinical examination).
Masking: Single (Participant)
Masking Description: Patients and the research team collecting follow up data will be blinded as to whether the person has had NeuroSAFE procedure. The surgeon and pathologist cannot be blinded to this.
Primary Purpose: Treatment
Official Title: Single Blinded, Multi-centre, Feasibility Study to Evaluate the Ability to Randomise Men With Prostate Cancer Into a Trial Comparing NeuroSAFE Robotic Assisted Radical Prostatectomy (RALP) to Standard Robotic Assisted Radical Prostatectomy
Actual Study Start Date : April 9, 2018
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : March 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: NeuroSAFE procedure
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
Procedure: NeuroSAFE 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 positive margin is reported by the pathologist, the entire neurovascular bundle on the affected side will be removed and sent for formal pathological examination.

No Intervention: Control
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.

Primary Outcome Measures :
  1. Recruitment rates [ Time Frame: 1 year ]
    Recruitment rates

  2. Study acceptability [ Time Frame: 1 year ]
    Proportion of eligible men accepting randomisation

Secondary Outcome Measures :
  1. Short term oncological and functional outcome (compound outcome) [ Time Frame: 1 years after surgery ]
    Proportion of men who are potent and continent with undetectable PSA and negative surgical margins at 1 year post surgery.

  2. Health economics [ Time Frame: 1 year from surgery ]
    Short term - Cost of treatment for incontinence, impotence and adjuvant treatment

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Only males can develop prostate cancer
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Men opting to undergo RALP for organ confined prostate cancer.
  2. Potent men (IIEF 22-25 not using PDE5i or other medications or vacuum pump)
  3. Men who are continent of urine (no self-reported urinary incontinence)
  4. Has given written informed consent

Exclusion Criteria:

  1. Unable to undergo robotic prostatectomy
  2. Known overactive bladder
  3. Previous treatment for prostate cancer
  4. Previous/current hormone treatment for prostate cancer
  5. Nerve sparing deemed futile due to locally advanced disease by surgeon and radiologist

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03317990

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Contact: Jack D Grierson, MRes 0207 679 9280

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United Kingdom
North Bristol NHS Trust Recruiting
Bristol, United Kingdom, BS10 5NB
Contact: Raj Persad         
NHS Greater Glasgow & Clyde Recruiting
Glasgow, United Kingdom
Contact: Imran Ahmad, PhD, MRCS         
University College London Hospital Recruiting
London, United Kingdom, NW1 2BU
Contact: Greg Shaw, MD         
Sheffield Teaching Hospitals NHS Foundation Trust Recruiting
Sheffield, United Kingdom, S10 2JF
Contact: Neil Oakley, MD         
Sponsors and Collaborators
University College, London
North Bristol NHS Trust
Sheffield Teaching Hospitals NHS Foundation Trust
University College London Hospitals
NHS Greater Glasgow and Clyde
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Principal Investigator: Greg L Shaw, MD University College, London

Publications of Results:
Other Publications:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: University College, London Identifier: NCT03317990     History of Changes
Other Study ID Numbers: 220262
First Posted: October 23, 2017    Key Record Dates
Last Update Posted: August 13, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: All data will be anonymised at source. Only anonymised data will be shared.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University College, London:
Prostate Cancer
Nerve sparing
Frozen section
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases