Evaluating the Effects of Frozen Section Technology on Oncological and Functional Outcomes at Radical Prostatectomy. (NSAFEPROOF)
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|ClinicalTrials.gov Identifier: NCT03317990|
Recruitment Status : Recruiting
First Posted : October 23, 2017
Last Update Posted : January 24, 2019
|Condition or disease||Intervention/treatment||Phase|
|Prostate Cancer||Procedure: NeuroSAFE procedure||Not Applicable|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||100 participants|
|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 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.|
|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|
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.
- Recruitment rates [ Time Frame: 1 year ]Recruitment rates
- Study acceptability [ Time Frame: 1 year ]Proportion of eligible men accepting randomisation
- 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.
- Health economics [ Time Frame: 1 year from surgery ]Short term - Cost of treatment for incontinence, impotence and adjuvant treatment
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03317990
|Contact: Jack D Grierson, MRes||0207 679 email@example.com|
|North Bristol NHS Trust||Recruiting|
|Bristol, United Kingdom, BS10 5NB|
|Contact: Raj Persad|
|University College London Hospital||Recruiting|
|London, United Kingdom, NW1 2BU|
|Contact: Greg Shaw, MD|
|Sheffield Teaching Hospitals NHS Foundation Trust||Not yet recruiting|
|Sheffield, United Kingdom, S10 2JF|
|Contact: Neil Oakley, MD|
|Principal Investigator:||Greg L Shaw, MD||University College, London|