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

Eoin Dinneen, Aiman Haider, Clare Allen, Alex Freeman, Tim Briggs, Senthil Nathan, Chris Brew-Graves, Jack Grierson, Norman R Williams, Raj Persad, Neil Oakley, Jim M Adshead, Hartwig Huland, Alexander Haese, Greg Shaw, Eoin Dinneen, Aiman Haider, Clare Allen, Alex Freeman, Tim Briggs, Senthil Nathan, Chris Brew-Graves, Jack Grierson, Norman R Williams, Raj Persad, Neil Oakley, Jim M Adshead, Hartwig Huland, Alexander Haese, Greg Shaw

Abstract

Introduction: Robot-assisted laparoscopic prostatectomy (RALP) offers potential cure for localised prostate cancer but is associated with considerable toxicity. Potency and urinary continence are improved when the neurovascular bundles (NVBs) are spared during a nerve spare (NS) RALP. There is reluctance, however, to perform NS RALP when there are concerns that the cancer extends beyond the capsule of the prostate into the NVB, as NS RALP in this instance increases the risk of a positive surgical margin (PSM). The NeuroSAFE technique involves intraoperative fresh-frozen section analysis of the posterolateral aspect of the prostate margin to assess whether cancer extends beyond the capsule. There is evidence from large observational studies that functional outcomes can be improved and PSM rates reduced when the NeuroSAFE technique is used during RALP. To date, however, there has been no randomised controlled trial (RCT) to substantiate this finding. The NeuroSAFE PROOF feasibility study is designed to assess whether it is feasible to randomise men to NeuroSAFE RALP versus a control arm of 'standard of practice' RALP.

Methods: NeuroSAFE PROOF feasibility study will be a multicentre, single-blinded RCT with patients randomised 1:1 to either NeuroSAFE RALP (intervention) or standard RALP (control). Treatment allocation will occur after trial entry and consent. The primary outcome will be assessed as the successful accrual of 50 men at three sites over 15 months. Secondary outcomes will be used to aid subsequent power calculations for the definitive full-scale RCT and will include rates of NS; PSM; biochemical recurrence; adjuvant treatments; and patient-reported functional outcomes on potency, continence and quality of life.

Ethics and dissemination: NeuroSAFE PROOF has ethical approval (Regional Ethics Committee reference 17/LO/1978). NeuroSAFE PROOF is supported by National Institute for Healthcare Research Research for Patient Benefit funding (NIHR reference PB-PG-1216-20013). Findings will be made available through peer-reviewed publications.

Trial registration number: NCT03317990.

Keywords: frozen section; nerve sparing; neurosafe; prostate cancer; robotic prostatectomy.

Conflict of interest statement

Competing interests: Within NeuroSAFE PROOF, laparoscopic ports are supplied by Applied Medical but Applied Medical has had no role in the design, analysis or collection of the data; in writing of the manuscript; or in the decision to submit the manuscript for publication.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1
Figure 1
NeuroSAFE PROOF feasibility study schema. EQ-5D-5L, EuroQuol-5 Dimension-5 Level Questionnaire; ICIQ, International Consultation on Incontinence Questionnaire; IIEF, International Index of Erectile Function; MDT, multidisciplinary team; NS, nerve sparing; PIS, Participant Information Sheet; PSA, Prostate Specific Antigen; RALP, r obot-assisted laparoscopic prostatectomy.

References

    1. Steineck G, Bjartell A, Hugosson J, et al. . Degree of preservation of the neurovascular bundles during radical prostatectomy and urinary continence 1 year after surgery. Eur Urol 2015;67:559–68. 10.1016/j.eururo.2014.10.011
    1. Savera AT, Kaul S, Badani K, et al. . Robotic radical prostatectomy with the "Veil of Aphrodite" technique: histologic evidence of enhanced nerve sparing. Eur Urol 2006;49:1065–74. 10.1016/j.eururo.2006.02.050
    1. Ficarra V, Sooriakumaran P, Novara G, et al. . Systematic review of methods for reporting combined outcomes after radical prostatectomy and proposal of a novel system: the survival, continence, and potency (SCP) classification. Eur Urol 2012;61:541–8. 10.1016/j.eururo.2011.11.042
    1. Sooriakumaran P, Ploumidis A, Nyberg T, et al. . The impact of length and location of positive margins in predicting biochemical recurrence after robot-assisted radical prostatectomy with a minimum follow-up of 5 years. BJU Int 2015;115:106–13. 10.1111/bju.12483
    1. Eichelberg C, Erbersdobler A, Haese A, et al. . Frozen section for the management of intraoperatively detected palpable tumor lesions during nerve-sparing scheduled radical prostatectomy. Eur Urol 2006;49:1011–8. 10.1016/j.eururo.2006.02.035
    1. de Rooij M, Hamoen EH, Witjes JA, et al. . Accuracy of Magnetic Resonance Imaging for Local Staging of Prostate Cancer: A Diagnostic Meta-analysis. Eur Urol 2016;70:233–45. 10.1016/j.eururo.2015.07.029
    1. Beyer B, Schlomm T, Tennstedt P, et al. . A feasible and time-efficient adaptation of NeuroSAFE for da Vinci robot-assisted radical prostatectomy. Eur Urol 2014;66:138–44. 10.1016/j.eururo.2013.12.014
    1. Schlomm T, Tennstedt P, Huxhold C, et al. . Neurovascular structure-adjacent frozen-section examination (NeuroSAFE) increases nerve-sparing frequency and reduces positive surgical margins in open and robot-assisted laparoscopic radical prostatectomy: experience after 11,069 consecutive patients. Eur Urol 2012;62:333–40. 10.1016/j.eururo.2012.04.057
    1. Mirmilstein G, Rai BP, Gbolahan O, et al. . The neurovascular structure-adjacent frozen-section examination (NeuroSAFE) approach to nerve sparing in robot-assisted laparoscopic radical prostatectomy in a British setting - a prospective observational comparative study. BJU Int 2018;121:854–62. 10.1111/bju.14078
    1. Fromont G, Baumert H, Cathelineau X, et al. . Intraoperative frozen section analysis during nerve sparing laparoscopic radical prostatectomy: feasibility study. J Urol 2003;170:1843–6. 10.1097/01.ju.0000092081.71167.34
    1. Kakiuchi Y, Choy B, Gordetsky J, et al. . Role of frozen section analysis of surgical margins during robot-assisted laparoscopic radical prostatectomy: a 2608-case experience. Hum Pathol 2013;44:1556–62. 10.1016/j.humpath.2012.12.011
    1. Lepor H, Kaci L. Role of intraoperative biopsies during radical retropubic prostatectomy. Urology 2004;63:499–502. 10.1016/j.urology.2003.10.017
    1. Gillitzer R, Thüroff C, Fandel T, et al. . Intraoperative peripheral frozen sections do not significantly affect prognosis after nerve-sparing radical prostatectomy for prostate cancer. BJU Int 2011;107:755–9. 10.1111/j.1464-410X.2010.09591.x
    1. Heinrich E, Schön G, Schiefelbein F, et al. . Clinical impact of intraoperative frozen sections during nerve-sparing radical prostatectomy. World J Urol 2010;28:709–13. 10.1007/s00345-010-0529-3
    1. Goharderakhshan RZ, Sudilovsky D, Carroll LA, et al. . Utility of intraoperative frozen section analysis of surgical margins in region of neurovascular bundles at radical prostatectomy. Urology 2002;59:709–14. 10.1016/S0090-4295(02)01539-X
    1. Elliott D, Husbands S, Hamdy FC, et al. . Understanding and improving recruitment to randomised controlled trials: Qualitative research approaches. Eur Urol 2017;72:789–98. 10.1016/j.eururo.2017.04.036
    1. Chan AW, Tetzlaff JM, Gøtzsche PC, et al. . SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ 2013;346:e7586 10.1136/bmj.e7586
    1. Ficarra V, Novara G, Ahlering TE, et al. . Systematic review and meta-analysis of studies reporting potency rates after robot-assisted radical prostatectomy. Eur Urol 2012;62:418–30. 10.1016/j.eururo.2012.05.046
    1. Sooriakumaran P, Srivastava A, Shariat SF, et al. . A multinational, multi-institutional study comparing positive surgical margin rates among 22393 open, laparoscopic, and robot-assisted radical prostatectomy patients. Eur Urol 2014;66:450–6. 10.1016/j.eururo.2013.11.018
    1. Akin O, Riedl CC, Ishill NM, et al. . Interactive dedicated training curriculum improves accuracy in the interpretation of MR imaging of prostate cancer. Eur Radiol 2010;20:995–1002. 10.1007/s00330-009-1625-x
    1. Tewari AK, Srivastava A, Huang MW, et al. . Anatomical grades of nerve sparing: a risk-stratified approach to neural-hammock sparing during robot-assisted radical prostatectomy (RARP). BJU Int 2011;108(6 Pt 2):984–92. 10.1111/j.1464-410X.2011.10565.x
    1. Vasdev N, Agarwal S, Rai BP, et al. . 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;9:93–103. 10.1159/000442860
    1. Rosen RC, Riley A, Wagner G, et al. . The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology 1997;49:822–30. 10.1016/S0090-4295(97)00238-0
    1. Ware JE, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992;30:473–83.
    1. Avery K, Abrams P, Chadwick M, et al. . Development and psychometric evaluation of the ICIQ urinary and bowel incontinence modules: The ICIQ-UI and ICIQ-BI. Neurourol Urodynam 2004;23(5-6):396–7.
    1. Herdman M, Gudex C, Lloyd A, et al. . Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res 2011;20:1727–36. 10.1007/s11136-011-9903-x
    1. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004;240:205–13. 10.1097/

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다