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Intra-operative Frozen Section for the Assessment of Margins during Radical Prostatectomy

Dinneen, Eoin; (2022) Intra-operative Frozen Section for the Assessment of Margins during Radical Prostatectomy. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Introduction Radical prostatectomy (RP) is associated with the unwanted significant long-term side-effects of erectile dysfunction and urinary incontinence. Nerve-sparing (NS) RP can mitigate or even totally avoid these treatment toxicities. However, in order to avoid positive surgical resection margins (PSM) and the attendant increased risk of prostate cancer (PCa) recurrence, NS RP is often eschewed in favour of RP wherein the neurovascular bundles are excised. Practice of NS RP around the world is far from uniform. Reproducible and well-evaluated methods to guide correct NS, and therefore optimal surgery, for men undergoing RP are largely lacking however over recent years there has been increasing interest in intra-operative frozen section (IFS) to achieve this optimal balance during RP. Methods & Results First, I present the results of our systematic review that highlighted the poor levels of evidence available on IFS during RP in relation to guiding NS. Within the limitations of the available evidence, the NeuroSAFE IFS technique may help increase NS during RP without increasing PSM or negatively influencing oncological outcomes. However, the systematic review noted that there were no prospective studies, no randomised studies, no studies including patient-reported outcome measures (PROMs), and almost no studies reporting on patient-centred outcomes as opposed to surgical and histological surrogates, such as NS status and PSM rates. Second, I present the methods and the results of a NeuroSAFE PROOF feasibility study. The design of the feasibility study was informed by the work included in the systematic review. The NeuroSAFE PROOF feasibility study was conducted by our group in order to assess whether a multi-site randomised controlled trial (RCT) of the NeuroSAFE technique would be acceptable and worthwhile. This study, which was the first RCT in the world of any IFS during RP, clearly showed that a definitive trial was feasible and secondary outcomes indicated merit in pursuing such a trial. I then secured funding by peer-reviewed, external competition for the conduct of the definitive NeuroSAFE PROOF RCT. Thus, thirdly, I present the design and preliminary results from the definitive RCT of the NeuroSAFE technique (NeuroSAFE PROOF). This trial will, once complete, for the first time provide level 1 evidence on the role of IFS during RP. The preliminary results presented in Chapter 6 include the peri-operative results on almost half of the final cohort and 12-months follow-up on 30% of the final trial population. There is already clear evidence that NS during RP is increased and PSM rates are reduced by using the NeuroSAFE technique. Additionally, though the number of observations on functional outcomes are fewer, there is evidence to suggest that functional outcomes such as erectile function and urinary continence recovery are improved in men who have undergone RP with the NeuroSAFE technique compared to men who have had RP without the NeuroSAFE technique. The results of a pre-defined sub-analysis suggest that the NeuroSAFE technique is of particular benefit in men who would have not otherwise had bilateral NS RP if they were in the control arm. Finally, I present the results of a single centre study evaluating the ability of MRI to predict extra-prostatic extension (EPE) of PCa tumour. This question is highly relevant given that EPE is usually considered the key contra-indication to NS RP. The results of this study, though based at one centre, indicate that in almost half of men, pre-operative MRI can rule out EPE and therefore NS may be safely undertaken without requiring the resource intensive NeuroSAFE technique. This study informed the sub-analysis outlined clearly in the NeuroSAFE PROOF RCT and, in the future, this study will form the basis of efforts to direct where, how, and in whom IFS is performed to improve outcomes following RP. Conclusions The NeuroSAFE technique is a legitimate method to increase the ability to NS during RP, which may in turn facilitate a reduction in the unwanted long-term treatment side-effects following, particularly in men who would not otherwise undergo NS RP. The final results of the NeuroSAFE PROOF RCT are awaited.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Intra-operative Frozen Section for the Assessment of Margins during Radical Prostatectomy
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10157509
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