Minimally invasive esophagectomy versus open surgery: is there an advantage?
Lesley Uttley, Fiona Campbell, Michael Rhodes, Anna Cantrell, Heather Stegenga & Myfanwy Lloyd-Jones Surgical Endoscopy And Other Interventional Techniques Official Journal of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) and European Association for Endoscopic Surgery (EAES) ISSN 0930-2794 Surg Endosc DOI 10.1007/s00464-013-3068-3
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Author's personal copy Surg Endosc DOI 10.1007/s00464-013-3068-3
and Other Interventional Techniques
LETTER TO THE EDITOR–REPLY
Minimally invasive esophagectomy versus open surgery: is there an advantage? Lesley Uttley • Fiona Campbell • Michael Rhodes Anna Cantrell • Heather Stegenga • Myfanwy Lloyd-Jones
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Received: 23 May 2013 / Accepted: 10 June 2013 Ó Springer Science+Business Media New York 2013
Hamilton and Griffiths [1] make a number of points in their letter to the editor responding to Uttley et al. [2]. We thank the authors for highlighting these trials and also agree with the argument that a randomized controlled trial (RCT) is the best way for a robust comparison of the two treatments. The authors cite a number of trials in their letter, including the CLASICC trial of laparoscopic versus open surgery for colorectal cancer [3] as an example of a good RCT in the field of open versus minimally invasive surgery. Although this trial may have disproved the ‘‘erroneous belief that laparoscopic surgery compromised surgical outcomes’’ [1], an RCT is not generally required to demonstrate safety. Safety can be demonstrated using other study designs without risking the survival of patients by randomizing some patients to what may not be the most appropriate form of surgery available. However, the CLASICC controlled study did demonstrate that laparoscopic surgery is not inferior to open surgery. This also is the current state of the evidence indicated by the literature comparing open and minimally invasive surgery in esophageal resection. The RCT is the most powerful tool in comparative effectiveness research. The main benefits of the RCT are that it allows an intervention to be compared against nothing (to ensure that it works) or to be compared with the best currently available treatment (to ensure that it works as well as the current treatment we already have or even better).
L. Uttley (&) F. Campbell M. Rhodes A. Cantrell H. Stegenga M. Lloyd-Jones School of Health and Related Research (ScHARR), University of Sheffield, Regent Court, 30 Regent Street, Sheffield S1 4DA, UK e-mail:
[email protected]
The crucial advantages of RCTs are randomization, blinding, and examination of relevant outcomes. These are discussed briefly in turn using the CLASICC trial as an example showing why conducting an RCT does not necessarily result in level 1 evidence.
Randomization Proper randomization is crucial to the RCT to ensure that it really is a fair test. However, in the CLASICC trial, randomization was stratified by the surgeon, the proposed site of the operation, the presence of liver metastases, and the preoperative radiotherapy administration. Stratifying by more than one variable can be problematic, and stratifying by more than two variables is not advisable [4]. The precise method of this stratified randomization in the CLASICC trial is not described. Therefore, the ‘‘randomized’’ element of this example was not adequately described and may not be akin to the gold standard evidence we expect to glean from an RCT. Without transparent reporting, readers cannot judge the reliability or validity of trial findings or extract information for systematic reviews [5–7].
Blinding For a full evaluation of interventions, patients and investigators ideally should be blinded to ensure that their own awareness of the treatment does not influence the patient (placebo/nocebo effect) or investigator perception of outcomes (reporting bias). To date, blinding has not been possible in comparing minimally invasive and open esophagectomy, but it currently is being explored [8].
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Allocation concealment at the stage of randomization also is vital to minimize bias and to ensure that trialists are unable to influence whether certain patients are allocated to a trial arm. It should be stated explicitly in trial publications whether patient allocation was concealed. This was not done in the CLASICC trial.
Examination of relevant primary outcomes The purported benefits of minimally invasive techniques compared with open procedures are reported in the CLASICC trial as ‘‘more rapid recovery, fewer complications, and shorter duration of hospital stay’’ [3]. The outcomes actually described in the report are short-term end points used ‘‘as surrogates to predict long-term clinical outcomes.’’ However, a further report, published 5 years later in 2010 did report the relevant outcomes of survival and suggested no difference between the groups in terms of long-term survival [9]. Interestingly, in the Biere et al. [10] investigation, another study cited by Hamilton and Griffiths [1], the authors stated: ‘‘Traditional open oesophageal resection is associated with a high morbidity and mortality rate. Furthermore, this approach involves long intensive care unit stay, in-hospital stay and long recovery period. Minimally invasive oesophagectomy could reduce the morbidity and accelerate the postoperative recovery.’’ However, the primary outcome reported in this study was pulmonary infection within the first 2 weeks after surgery and during the whole stay in the hospital. This cannot be considered as the relevant primary outcome with reference to the decision problem outlined by the authors as whether minimally invasive esophagectomy reduces overall morbidity compared with open esophagectomy. Any RCT that does not examine relevant primary outcomes cannot be considered an effective use of resources. We agree with the conclusion of Hamilton and Griffiths [1] that ‘‘it is only with such robust level 1 evidence that this exciting branch of upper gastrointestinal surgery can truly evolve.’’ However, the evidence from the trials cited in this example may not fit the criteria for level 1 evidence due to the reasons illustrated earlier. Calling a trial an RCT does not necessarily make it the level 1 evidence sought and highly regarded. Poorly conducted RCTs are more likely to result when RCTs are difficult to conduct [11]. Feasibility studies such as the ROMIO trial [8] need to be conducted to establish critical intervention components, and trial protocols should be published prospectively [12]. Such feasibility studies could inform a well-planned, high-quality RCT and provide a genuinely fair test of two complex procedures [13].
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In the meantime, systematic reviews and metaanalyses of prospective nonrandomized designs that minimize known biases should be considered as pragmatic alternatives to costly RCTs that may be too hastily designed to be informative. Disclosures Lesley Uttley, Fiona Campbell, Michael Rhodes, Anna Cantrell, Heather Stegenga, and Myfanwy Lloyd-Jones have no conflicts of interest or financial ties to disclose.
References 1. Hamilton E, Griffiths E (2013) Letter to the editor: commentary on Uttley L, Campbell F, Rhodes M et al.: minimally invasive oesophagectomy versus open surgery: is there an advantage? Surg Endosc 27:724–731 2. Uttley L, Campbell F, Rhodes M, Cantrell A, Stegenga H, LloydJones M (2013) Minimally invasive oesophagectomy versus open surgery: is there an advantage? Surg Endosc 27:724–731 3. Guillou PJ, Quirke P, Thorpe H, Walker J, Jayne DG, Smith AM et al (2005) Short-term end points of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer (MRC CLASICC trial): multicentre, randomised controlled trial. Lancet 365:1718–1726 4. Torgerson DJ, Torgerson CJ (2008) Designing randomised trials in health, education and the social sciences. Palgrave Macmillan, Hampshire 5. Moher D, Hopewell S, Schulz KF, Montori V, Gotzsche PC, Devereaux PJ et al (2010) CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ 24:340 6. Moher D, Schulz K, Altman D (2001) The CONSORT statement: revised recommendations for improving the quality of reports of parallel group randomized trials. BMC Med Res Method 1:2 7. Schulz KFCI (1994) Assessing the quality of randomization from reports of controlled trials published in obstetrics and gynecology journals. JAMA 272:125–128 8. Metcalfe C (2013) The ROMIO trial: randomised oesophagectomy: minimally invasive or open: a feasibility study. National Institute for Health Research: Health Technology Assessment programme project in progress. http://www.hta.ac.uk/project/ 2827.asp. Accessed 21 June 2013 9. Jayne DG, Guillou PJ, Thorpe H, Quirke P, Copeland J, Smith AM et al (2007) Randomized trial of laparoscopic-assisted resection of colorectal carcinoma: 3-year results of the UK MRC CLASICC Trial Group. J Clin Oncol 25:3061–3068 10. Biere SS, van Berge Henegouwen MI, Maas KW, Bonavina L, Rosman C, Garcia JR et al (2012) Minimally invasive versus open oesophagectomy for patients with oesophageal cancer: a multicentre, open-label, randomised controlled trial. Lancet 379(9829): 1887–1892 11. McCulloch P, Taylor I, Sasako M, Lovett B, Griffin D (2002) Randomised trials in surgery: problems and possible solutions. BMJ 324:1448–1451 12. Godlee F (2001) Publishing study protocols: making them visible will improve registration, reporting, and recruitment. BMC News Views 2:4 13. Avery KN, Barham CP, Berrisford R, Blazeby JM, Blencowe NS, Donovan J et al (2005) Understanding surgical interventions in RCTs: the need for better methodology. Lancet 381:27–28
