THE AUSTRALASIAN LAPARAOSCOPIC COLON CANCER STUDY

摘要

The Australasian Laparoscopic Colon Cancer Study (ALCCaS) is a non-inferiority randomized controlled trial (RCT) comparing laparoscopic and open surgical treatments of right-sided and left-sided potentially curable colon cancer. It is not often that large and complex multicentre surgical trials are jointly undertaken between Australia and New Zealand and ALCCaS methodological coherence with other major international trials adds an unprecedented analytical dimension. This paper emphasizes some of the implications and issues that transcend the nuts, bolts and results of ALCCaS. Similar international studies (e.g., Clinical Outcomes of Surgical Therapy (COST), Colon Cancer Laparoscopic or Open Resection, Conventional versus Laparoscopic-Assisted Surgery in Patients with Colorectal Cancer (CLASICC) and ALCCaS) set against different economic and cultural backgrounds achieve clinical consensus by reducing both acknowledged and unrecognized regional variables. These related studies also allow economic, social and clinical variables to be identified and their contributions to outcomes assessed. In addition, close alignment of methods and outcomes between important RCT increases the evidence base and statistical power to assess combined data that can be stratified beyond the primary and secondary clinical outcomes and quality of life assessments of any single trial. The original accrual target of 1260 patients proved unattainable within a practical time frame. An adjustment to 600, to detect a mortality difference of 11% at 5 years, was approved by the Health Research Council of New Zealand-appointed international Data Monitoring Committee (DMC) and was attained in March 2005 in the expectation of combining ALCCaS with other RCT outcome data. Patient recruitment to surgical trials is a problem that is not confined to ALCCaS. Both the COST and CLASICC trials were required to reduce their accrual targets to provide timely operative and teaching guidance.1,2 The chief factors limiting accrual were the number of surgeons enrolled and their patient recruitment to ALCCaS. This was influenced by the stringent credentialing criteria, surgeon and/or patient preference for a procedure,3 increased laparoscopic colonic resection (LCR) time and reluctance to randomize private patients. There were also delays in gaining ethics approval in individual centres that could have been improved by centralization of the process. Surgeon credentialing, as specified in the COST protocol, was based on an audited videotape of an LCR and 20 operative reports describing oncologically appropriate laparoscopic procedures. It must be said that, at the outset of the COST study (from which ALCCaS derived its protocols) the criteria on which qualified participation and learning curve prediction were based may have been arbitrary and unproved. Whatever criteria are appropriate may not be a simple matter to decide, but arguably what was done for ALCCaS seemed to work. Procedure credentialing and the achievement of short-term results similar to other important RCT raise several points. First, the willingness to undergo close peer scrutiny illustrates the integrity of surgeons and their desire to achieve excellence. Some may also think that it emphasizes the potential for the future adoption of video evidence in vocational examinations and staff appointments. Moreover, the amalgamation of coherent international RCT trial data provides not only information about new therapies, but also gives an historical perspective on well-defined, conventional therapies and outcomes for comparison by surgeons in the future. With regard for that perspective the question might be put: if all the compatible RCT show equivalence or non-inferiority for survival and recurrence and the benefits of minimally invasive surgery are modest and largely subjective, what is the ‘gold standard’? Is it LCR or open colon resection (OCR)? Are the level 1 data to be considered together or separately? In prac