Laparoscopically Assisted versus Open Colectomy for Colon Cancer
http://www.100md.com
《新英格兰医药杂志》
To the Editor: Nelson et al. report on the Clinical Outcomes of Surgical Therapy (COST) trial, which compared laparoscopically assisted colectomy with open colectomy for colon cancer (May 13 issue).1 Unfortunately, the methods described in their article fail to support the claim of noninferiority,2 for several reasons. First, the authors do not explicitly define a noninferiority boundary. Second, the statistical methods described in the article are those of a failed superiority trial rather than a noninferiority trial. Third, one approach to demonstrating noninferiority is to show that the upper limit of the one-sided 95 percent confidence interval for the hazard ratio is less than the noninferiority boundary. We have calculated that this value is 1.16 for the risk of death and 1.11 for the risk of recurrence with laparoscopic treatment.
We can conclude with 95 percent certainty that patients who are treated laparoscopically have at most a 16 percent increase in the risk of death and an 11 percent increase in the risk of recurrence. In the absence of a predefined noninferiority boundary, the individual reader must decide whether these are potentially clinically important risks.
Jill Tinmouth, M.D.
St. Michael's Hospital
Toronto, ON M5B 1W8, Canada
tinmouthj@smh.toronto.on.ca
George Tomlinson, Ph.D.
University of Toronto
Toronto, ON M5G 2C4, Canada
References
The Clinical Outcomes of Surgical Therapy Study Group. A comparison of laparoscopically assisted and open colectomy for colon cancer. N Engl J Med 2004;350:2050-2059.
Greene WL, Concato J, Feinstein AR. Claims of equivalence in medical research: are they supported by the evidence? Ann Intern Med 2000;132:715-722.
To the Editor: In the report on the comparison of laparoscopically assisted and open colectomy for colon cancer, details concerning perioperative management are absent. The beneficial effect of fast-track multimodal rehabilitation with respect to the short-term outcome has been clearly demonstrated.1 Epidural analgesia, allowing early ambulation and oral nutrition, improves convalescence after various types of surgery, such as abdominothoracic surgical interventions in the gastrointestinal tract,2 major urologic surgery,3 and even coronary-artery bypass grafting.4 Kehlet and Mogensen5 showed that with the use of such a clinical pathway, the median hospital stay was two days after open colonic resection.
Thus, the short-term improvement due to a rehabilitation program including thoracic epidural analgesia probably exceeds the slight benefits of laparoscopically assisted colectomy demonstrated by Nelson et al. Consequently, in a cost-effectiveness analysis of the surgical technique, anesthesia care and postoperative management should be carefully studied.
Nicholas Dalibon, M.D.
Marc Moutafis, M.D.
Marc Fischler, M.D.
H?pital Foch
92150 Suresnes, France
n.dalibon@hopital-foch.org
References
Kehlet H, Dahl JB. Anaesthesia, surgery, and challenges in postoperative recovery. Lancet 2003;362:1921-1928.
Henriksen MG, Jensen MB, Hansen HV, Jespersen TW, Hessov L. Enforced mobilization, early oral feeding, and balanced analgesia improve convalescence after colorectal surgery. Nutrition 2002;18:147-152.
Brodner G, Van Aken H, Hertle L, et al. Multimodal perioperative management -- combining thoracic epidural analgesia, forced mobilization, and oral nutrition -- reduces hormonal and metabolic stress and improves convalescence after major urologic surgery. Anesth Analg 2001;92:1594-1600.
Scott NB, Turfrey DJ, Ray DA, et al. A prospective randomized study of the potential benefits of thoracic epidural anesthesia and analgesia in patients undergoing coronary artery bypass grafting. Anesth Analg 2001;93:528-535.
Kehlet H, Mogensen T. Hospital stay of 2 days after open sigmoidectomy with a multimodal rehabilitation programme. Br J Surg 1999;86:227-230.
The authors reply: The points raised by Drs. Tinmouth and Tomlinson highlight the evolving definitions and statistical issues regarding noninferiority trials. This trial was designed in 1993 specifically to examine whether laparoscopically assisted colectomy was inferior to standard open colectomy; formal statistical methods for noninferiority trials had not yet been described in the literature. The first statistical reference to noninferiority trials dates back to 1997.1 The trial was designed with 81 percent power to detect inferiority if the ratio of the recurrence rate in the group treated with laparoscopically assisted colectomy to the rate in the open-colectomy group was 1.29, with the use of one-sided testing. Superiority testing was not in the protocol, nor were such analyses conducted. The methods used were approved by statisticians from each of the seven participating National Cancer Institute cooperative groups, were reported in 1995,2 and were rigorously followed. We agree that careful examination of the confidence intervals is helpful, to consider the range of possible hazard ratios supported by the data. To define more accurately the range of possible hazard ratios, a pooled analysis that includes data from two other international trials (the Colon Carcinoma Laparoscopic or Open Resection trial and the Conventional versus Laparoscopic Assisted Surgery in Colorectal Cancer trial) comparing the two surgical approaches is under way.
Dr. Dalibon and colleagues comment on the evolving nature of postoperative care and how changes in practice might affect recovery. The 66 surgeons who enrolled patients in the COST trial represent a diverse cross section of surgical practices throughout the United States and Canada — that is, the trial represents the contemporary standard of care. Surgeons agreed to implement the same progressive recovery practice in both groups of patients. Consistent recovery benefits were demonstrated for laparoscopically assisted colectomy across multiple end points. As newer options for reducing recovery time, such as fast-track multimodal rehabilitation, are described, they too should be investigated in multi-institutional, prospective, randomized comparisons. A cost-effectiveness analysis of the COST study is being performed. Furthermore, as laparoscopic techniques evolve to include advances such as incisionless proctocolectomy, the cost–benefit ratios for such advances will require rigorous examination. The goals of minimizing surgical trauma, expediting postoperative recovery, preserving the quality of life, and preserving oncologic effectiveness are relevant to all advances in the surgical management of colon cancer, and such innovations should be considered complementary.
Heidi Nelson, M.D.
Daniel J. Sargent, Ph.D.
Mayo Clinic
Rochester, MN 55905
nelsonh@mayo.edu
References
Huque MF, Sankoh AJ, Rashid MM. Large sample inference for non-inferiority and clinical equivalence trials and the impact of multiple end points. ASA Proc Biopharm Sec 1997:224-9.
Nelson H, Weeks JC, Wieand HS. Proposed phase III trial comparing laparoscopic-assisted colectomy versus open colectomy for colon cancer. J Natl Cancer Inst Monogr 1995;19:51-56.
We can conclude with 95 percent certainty that patients who are treated laparoscopically have at most a 16 percent increase in the risk of death and an 11 percent increase in the risk of recurrence. In the absence of a predefined noninferiority boundary, the individual reader must decide whether these are potentially clinically important risks.
Jill Tinmouth, M.D.
St. Michael's Hospital
Toronto, ON M5B 1W8, Canada
tinmouthj@smh.toronto.on.ca
George Tomlinson, Ph.D.
University of Toronto
Toronto, ON M5G 2C4, Canada
References
The Clinical Outcomes of Surgical Therapy Study Group. A comparison of laparoscopically assisted and open colectomy for colon cancer. N Engl J Med 2004;350:2050-2059.
Greene WL, Concato J, Feinstein AR. Claims of equivalence in medical research: are they supported by the evidence? Ann Intern Med 2000;132:715-722.
To the Editor: In the report on the comparison of laparoscopically assisted and open colectomy for colon cancer, details concerning perioperative management are absent. The beneficial effect of fast-track multimodal rehabilitation with respect to the short-term outcome has been clearly demonstrated.1 Epidural analgesia, allowing early ambulation and oral nutrition, improves convalescence after various types of surgery, such as abdominothoracic surgical interventions in the gastrointestinal tract,2 major urologic surgery,3 and even coronary-artery bypass grafting.4 Kehlet and Mogensen5 showed that with the use of such a clinical pathway, the median hospital stay was two days after open colonic resection.
Thus, the short-term improvement due to a rehabilitation program including thoracic epidural analgesia probably exceeds the slight benefits of laparoscopically assisted colectomy demonstrated by Nelson et al. Consequently, in a cost-effectiveness analysis of the surgical technique, anesthesia care and postoperative management should be carefully studied.
Nicholas Dalibon, M.D.
Marc Moutafis, M.D.
Marc Fischler, M.D.
H?pital Foch
92150 Suresnes, France
n.dalibon@hopital-foch.org
References
Kehlet H, Dahl JB. Anaesthesia, surgery, and challenges in postoperative recovery. Lancet 2003;362:1921-1928.
Henriksen MG, Jensen MB, Hansen HV, Jespersen TW, Hessov L. Enforced mobilization, early oral feeding, and balanced analgesia improve convalescence after colorectal surgery. Nutrition 2002;18:147-152.
Brodner G, Van Aken H, Hertle L, et al. Multimodal perioperative management -- combining thoracic epidural analgesia, forced mobilization, and oral nutrition -- reduces hormonal and metabolic stress and improves convalescence after major urologic surgery. Anesth Analg 2001;92:1594-1600.
Scott NB, Turfrey DJ, Ray DA, et al. A prospective randomized study of the potential benefits of thoracic epidural anesthesia and analgesia in patients undergoing coronary artery bypass grafting. Anesth Analg 2001;93:528-535.
Kehlet H, Mogensen T. Hospital stay of 2 days after open sigmoidectomy with a multimodal rehabilitation programme. Br J Surg 1999;86:227-230.
The authors reply: The points raised by Drs. Tinmouth and Tomlinson highlight the evolving definitions and statistical issues regarding noninferiority trials. This trial was designed in 1993 specifically to examine whether laparoscopically assisted colectomy was inferior to standard open colectomy; formal statistical methods for noninferiority trials had not yet been described in the literature. The first statistical reference to noninferiority trials dates back to 1997.1 The trial was designed with 81 percent power to detect inferiority if the ratio of the recurrence rate in the group treated with laparoscopically assisted colectomy to the rate in the open-colectomy group was 1.29, with the use of one-sided testing. Superiority testing was not in the protocol, nor were such analyses conducted. The methods used were approved by statisticians from each of the seven participating National Cancer Institute cooperative groups, were reported in 1995,2 and were rigorously followed. We agree that careful examination of the confidence intervals is helpful, to consider the range of possible hazard ratios supported by the data. To define more accurately the range of possible hazard ratios, a pooled analysis that includes data from two other international trials (the Colon Carcinoma Laparoscopic or Open Resection trial and the Conventional versus Laparoscopic Assisted Surgery in Colorectal Cancer trial) comparing the two surgical approaches is under way.
Dr. Dalibon and colleagues comment on the evolving nature of postoperative care and how changes in practice might affect recovery. The 66 surgeons who enrolled patients in the COST trial represent a diverse cross section of surgical practices throughout the United States and Canada — that is, the trial represents the contemporary standard of care. Surgeons agreed to implement the same progressive recovery practice in both groups of patients. Consistent recovery benefits were demonstrated for laparoscopically assisted colectomy across multiple end points. As newer options for reducing recovery time, such as fast-track multimodal rehabilitation, are described, they too should be investigated in multi-institutional, prospective, randomized comparisons. A cost-effectiveness analysis of the COST study is being performed. Furthermore, as laparoscopic techniques evolve to include advances such as incisionless proctocolectomy, the cost–benefit ratios for such advances will require rigorous examination. The goals of minimizing surgical trauma, expediting postoperative recovery, preserving the quality of life, and preserving oncologic effectiveness are relevant to all advances in the surgical management of colon cancer, and such innovations should be considered complementary.
Heidi Nelson, M.D.
Daniel J. Sargent, Ph.D.
Mayo Clinic
Rochester, MN 55905
nelsonh@mayo.edu
References
Huque MF, Sankoh AJ, Rashid MM. Large sample inference for non-inferiority and clinical equivalence trials and the impact of multiple end points. ASA Proc Biopharm Sec 1997:224-9.
Nelson H, Weeks JC, Wieand HS. Proposed phase III trial comparing laparoscopic-assisted colectomy versus open colectomy for colon cancer. J Natl Cancer Inst Monogr 1995;19:51-56.