- ALCCaS is a multi-center randomized controlled trial comparing laparoscopic and open surgery for colon cancer in Australia and New Zealand that recruited 600 patients between 1999-2008. - The primary aims are to compare 5-year mortality and tumor recurrence rates between the two surgical methods. Secondary aims look at short-term outcomes like complications, recovery time, and costs. - Over the study period, 592 patients were recruited across 7 centers by 34 surgeons. Data collection is now complete and results will be analyzed to determine if laparoscopic surgery is as safe and effective as open surgery for colon cancer.

1. ALCCaS Australasian Laparoscopic Colon Cancer Study

2. Randall Allardyce ALCCaS Co-Principal investigator Department of Surgery Christchurch School of Medicine And Health Sciences Christchurch, New Zealand This presentation is made on behalf of the ALCCaS Group

3. The ALCCaS Group in alphabetical order Surgeons P. Bagshaw, N. Barwoods, P. Carne, S. Chew, D. Clark, J. Evans, I. Faragher, G. Fielding, F. Frizelle, J. Hansen, J. Hayes, P. Hewett, M. Johnston, E. Juhasz, A. Karatassas, A. Luck, J. Lumley, G. Makin, I. Martin, J. McCall, P. McMurrick, M. Morgan, L. Nathanson, N. O’Rourke, N. Pathma-Nathan, D. Perera, A. Polglase, G. Poole, M. Rickard, N. Rieger, D. Rodda, J. Rutherford, P. Sitzler, M. Solomon, A. Stevenson, B. Stewart, R. Stitz Pathologist J. Jass Study Manager J.S. Smith Biostatistician C. Frampton Principal Investigators R. Allardyce P. Bagshaw F. Frizelle P. Hewett

4. ALCCaS disclaimer “ These results are only part of the information necessary for making an informed choice between laparoscopic and open surgery for colon cancer. ALCCaS findings about the relative benefits and risks of laparoscopic and open surgery are contingent on the primary aims of recurrence and survival. Recurrence and survival data will be published after five years follow-up of all study patients.”

6. The questions Safe and oncologically comparable? Intra-operative parameters Blood loss, duration of operation, tumour resection margins, lymph node clearance and adverse events Post-operative measures Pain, ileus, length of stay, wound site recurrence, 30d mortality, QOL, treatment costs, relative cost-effectiveness

7. Early clinical reports Few studies with good tumour stage matching between Lap and Open groups A few blinded pathologists Most studies were small and statistically limited Data for peri-op mortality, follow-up, relative risk measurements was poor Historical findings were commonly cited 3 y cancer recurrence data was limited

8. The risk of wound implantation Unexpected mets following lap procedures suggested the rate might exceed open surgery 2 early RC trials reported no wound recurrences (Lacy, et al 1995, Vukasin et al. 1996) Lap-assisted colectomy recalled experience with extracorporeal colon Ca resection (Paul, 1912, von Mikulicz, 1903)

9. Laparoscopic or Open?

10. Morris Franklin did it his way

11. On the horns of a dilemma

12. A need for PRC trials Am Soc of Colon & Rectal Surgeons ASERNIP-S COST (USA) CLASICC (UK) COLOR (EU & Scand) Braga et al (Italy) ALCCaS (AUS & NZ)

13. Coherence with COST protocols “ A phase III Prospecitve Randomised Trial Comparing Laparoscopic-Assisted Colectomy Versus Open Colectomy for Colon Cancer” provided by Robert W. Beart (Southwestern Oncology Group) Heidi Nelson (North Central Cancer Treatment Group)

14. Could we talk to each other?

15. Funding Feasibility Study 1996 Robt. McLelland Trust, Trust Bank Canterbury J.R. Mackenzie Trust ALCCaS 1997--- Johnson & Johnson Medical (NZ) Johnson & Johnson Medical Pty. Ltd. HRCNZ NH&MRC of Australia Canterbury Medical Research Foundation

16. Data Monitoring Committee Professor Tom Fleming (Chair), Seattle Emeritus Professor Tom Reeve, Sydney Assoc Professor John McCall, Auckland Dr Katrina Sharples, Dunedin Dr Ralph Stewart, Auckland Dr Andrew Moore, Dunedin Dr Anthony Rodgers, Auckland

17. ALCCaS Multi-centre Australia – New Zealand prospective, randomised, controlled clinical study comparing laparoscopic and conventional open surgery for right- and left-sided colon cancer in adults

18. Method Recruit 600 Pts with single colon Ca Randomly allocate to lap or open surgery Primary aims 5 year mortality Tumour recurrence Secondary aims safety (complications, recovery, 30d mortality) QOL, costs, short term mortality & recurrence

19. Data collectors Shona Smith (Chch) Vicki Allen (Q’land) Jacqueline Stephens (S Aus) Karen Pollock (Akl-NS) Melanie Thornton (Chch) Helen Mason (Vic) Anne Davidson (Dun) Christine Merlino (NSW) Jo Edwards (Ballarat)

20. Results Data for 592 Pts has been collected 2008 person years of follow-up 231 Pts have been assessed at 5 years

21. Number of recruiting surgeons and patients per centre 96 7 48 59 203 188 Patients 6 1 4 8 10 5 Surgeons NZ WA NSW Victoria Q’land Sth Aus Centre

22. Annual recruitment by geographic centre 601 7 48 59 203 188 96 CENTRE TOTAL 13 3 1 5 3 1 2005 120 4 10 11 31 48 16 2004 117 22 10 27 40 18 2003 95 8 7 26 40 14 2002 88 5 15 20 26 22 2001 80 2 14 37 18 9 2000 68 2 51 9 6 1999 20 6 4 10 1998 YR TOTAL WA NSW Vic Q'land S Aus NZ Date

23. Patient recruitment was not even 5/28 Australian surgeons did not recruit 2 Sth Aus surgeons entered 156 patients 2 Q’land surgeons entered 147 patients 2 NZ surgeons entered 81 patients 6 surgeons = 384 23 surgeons = 210

24. Publications Committee New Zealand Randall Allardyce Phil Bagshaw Frank Frizelle Chris Frampton Shona Smith Australia Peter Hewett Nick Rieger Michael Solomon Andrew Stevenson

25. Points for consideration The value of mutually supportive studies Barriers to patient recruitment Protection of data integrity (blinding & bias) Publication of short-term data Role of the DMC Lack of funding history for large surgical trials Data audit (accuracy and completeness) Agreement on publication strategy and processes

26. ALCCaS will conclude with 592 patients in March 2010