ALCCaSALCCaS

Australasian Laparoscopic Australasian Laparoscopic Colon Cancer StudyColon Cancer Study

Randall AllardyceRandall Allardyce

ALCCaS Co-Principal investigatorALCCaS Co-Principal investigator

Department of SurgeryDepartment of SurgeryChristchurch School of MedicineChristchurch School of Medicine

And Health SciencesAnd Health SciencesChristchurch, New ZealandChristchurch, New Zealand

This presentation is made This presentation is made on behalf of the ALCCaS Groupon behalf of the ALCCaS Group

The ALCCaS GroupThe ALCCaS Groupin alphabetical orderin alphabetical order

SurgeonsSurgeonsP. Bagshaw, N. Barwoods, P. Bagshaw, N. Barwoods, P. Carne, S. Chew, P. Carne, S. Chew, D. Clark, J. Evans, I. Faragher, D. Clark, J. Evans, I. Faragher, G. Fielding, F. Frizelle, J. Hansen,G. Fielding, F. Frizelle, J. Hansen,J. Hayes, P. Hewett, M. Johnston,J. Hayes, P. Hewett, M. Johnston,E. Juhasz, A. Karatassas, A. Luck, E. Juhasz, A. Karatassas, A. Luck, J. Lumley, G. Makin, I. Martin, J. Lumley, G. Makin, I. Martin, J. McCall, P. McMurrick, J. McCall, P. McMurrick, M. Morgan, L. Nathanson, M. Morgan, L. Nathanson, N. O’Rourke, N. Pathma-Nathan,N. O’Rourke, N. Pathma-Nathan,D. Perera, A. Polglase, G. Poole, D. Perera, A. Polglase, G. Poole, M. Rickard, N. Rieger, D. Rodda, M. Rickard, N. Rieger, D. Rodda, J. Rutherford, P. Sitzler, J. Rutherford, P. Sitzler, M. Solomon, A. Stevenson, M. Solomon, A. Stevenson, B. Stewart, R. StitzB. Stewart, R. Stitz

PathologistPathologistJ. JassJ. Jass

Study ManagerStudy ManagerJ.S. SmithJ.S. Smith

BiostatisticianBiostatisticianC. FramptonC. Frampton

Principal InvestigatorsPrincipal InvestigatorsR. AllardyceR. AllardyceP. BagshawP. BagshawF. FrizelleF. FrizelleP. HewettP. Hewett

ALCCaS disclaimerALCCaS disclaimer

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

The questionsThe questions

Safe and oncologically comparable?Safe and oncologically comparable? Intra-operative parametersIntra-operative parameters

– Blood loss, duration of operation, tumour Blood loss, duration of operation, tumour resection margins, lymph node clearance and resection margins, lymph node clearance and adverse eventsadverse events

Post-operative measuresPost-operative measures– Pain, ileus, length of stay, wound site Pain, ileus, length of stay, wound site

recurrence, 30d mortality, QOL, treatment recurrence, 30d mortality, QOL, treatment costs, relative cost-effectivenesscosts, relative cost-effectiveness

Early clinical reportsEarly clinical reports

Few studies with good tumour stage Few studies with good tumour stage matching between Lap and Open groupsmatching between Lap and Open groups

A few blinded pathologistsA few blinded pathologists Most studies were small and statistically Most studies were small and statistically

limitedlimited Data for peri-op mortality, follow-up, relative Data for peri-op mortality, follow-up, relative

risk measurements was poorrisk measurements was poor Historical findings were commonly citedHistorical findings were commonly cited 3 y cancer recurrence data was limited3 y cancer recurrence data was limited

The risk of wound implantationThe risk of wound implantation

Unexpected mets following lap procedures Unexpected mets following lap procedures suggested the rate might exceed open surgerysuggested the rate might exceed open surgery

2 early RC trials reported no wound recurrences 2 early RC trials reported no wound recurrences (Lacy, et al 1995, Vukasin et al. 1996)(Lacy, et al 1995, Vukasin et al. 1996)

Lap-assisted colectomy recalled experience with Lap-assisted colectomy recalled experience with extracorporeal colon Ca resection (Paul, 1912, extracorporeal colon Ca resection (Paul, 1912, von Mikulicz, 1903)von Mikulicz, 1903)

Laparoscopic or Open?

Morris Franklin did it his wayMorris Franklin did it his way

On the horns of a dilemmaOn the horns of a dilemma

A need for PRC trialsA need for PRC trials

Am Soc of Colon & Rectal SurgeonsAm Soc of Colon & Rectal Surgeons ASERNIP-SASERNIP-S

– COST (USA)COST (USA)– CLASICC (UK)CLASICC (UK)– COLOR (EU & Scand)COLOR (EU & Scand)– Braga et al (Italy)Braga et al (Italy)– ALCCaS (AUS & NZ)ALCCaS (AUS & NZ)

Coherence with COST protocolsCoherence with COST protocols

““A phase III Prospecitve Randomised Trial A phase III Prospecitve Randomised Trial Comparing Laparoscopic-Assisted Colectomy Comparing Laparoscopic-Assisted Colectomy Versus Open Colectomy for Colon Cancer”Versus Open Colectomy for Colon Cancer”

provided by provided by

Robert W. BeartRobert W. Beart (Southwestern Oncology Group)(Southwestern Oncology Group)

Heidi NelsonHeidi Nelson (North Central Cancer Treatment Group)(North Central Cancer Treatment Group)

Could we talk to each other?

FundingFunding

Feasibility Study 1996Feasibility Study 1996– Robt. McLelland Trust, Trust Bank CanterburyRobt. McLelland Trust, Trust Bank Canterbury– J.R. Mackenzie TrustJ.R. Mackenzie Trust

ALCCaS 1997---ALCCaS 1997---– Johnson & Johnson Medical (NZ)Johnson & Johnson Medical (NZ)– Johnson & Johnson Medical Pty. Ltd.Johnson & Johnson Medical Pty. Ltd.– HRCNZHRCNZ– NH&MRC of AustraliaNH&MRC of Australia– Canterbury Medical Research FoundationCanterbury Medical Research Foundation

Data Monitoring CommitteeData Monitoring Committee

Professor Tom Fleming (Chair), SeattleProfessor Tom Fleming (Chair), Seattle Emeritus Professor Tom Reeve, SydneyEmeritus Professor Tom Reeve, Sydney Assoc Professor John McCall, AucklandAssoc Professor John McCall, Auckland Dr Katrina Sharples, DunedinDr Katrina Sharples, Dunedin Dr Ralph Stewart, AucklandDr Ralph Stewart, Auckland Dr Andrew Moore, DunedinDr Andrew Moore, Dunedin Dr Anthony Rodgers, AucklandDr Anthony Rodgers, Auckland

ALCCaSALCCaS

Multi-centre Australia – New ZealandMulti-centre Australia – New Zealand

prospective, randomised, controlled prospective, randomised, controlled

clinical study comparing laparoscopic clinical study comparing laparoscopic

and conventional open surgery for and conventional open surgery for

right- and left-sided colon cancer in adultsright- and left-sided colon cancer in adults

MethodMethod

Recruit 600 Pts with single colon CaRecruit 600 Pts with single colon Ca Randomly allocate to lap or open surgeryRandomly allocate to lap or open surgery Primary aimsPrimary aims

– 5 year mortality5 year mortality– Tumour recurrence Tumour recurrence

Secondary aimsSecondary aims– safety (complications, recovery, 30d mortality)safety (complications, recovery, 30d mortality)– QOL, costs, short term mortality & recurrenceQOL, costs, short term mortality & recurrence

Data collectorsData collectors

Shona Smith (Chch)Shona Smith (Chch) Vicki Allen (Q’land)Vicki Allen (Q’land) Jacqueline Jacqueline

Stephens (S Aus)Stephens (S Aus) Karen Pollock (Akl-NS)Karen Pollock (Akl-NS) Melanie Thornton Melanie Thornton

(Chch)(Chch)

Helen Mason (Vic)Helen Mason (Vic) Anne Davidson (Dun)Anne Davidson (Dun) Christine Merlino Christine Merlino

(NSW)(NSW) Jo Edwards (Ballarat)Jo Edwards (Ballarat)

ResultsResults

Data for 592 Pts has been collectedData for 592 Pts has been collected 2008 person years of follow-up2008 person years of follow-up 231 Pts have been assessed at 5 years231 Pts have been assessed at 5 years

Number of recruiting surgeons Number of recruiting surgeons and patients per centre and patients per centre

Centre Sth Aus Q’land Victoria NSW WA NZ

Surgeons 5 10 8 4 1 6

Patients 188 203 59 48 7 96

Annual recruitment by geographic Annual recruitment by geographic centrecentre

Date NZ S Aus Q'land Vic NSW WA YR TOTAL

1998 10 4 6 20

1999 6 9 51 2 68

2000 9 18 37 14 2 80

2001 22 26 20 15 5 88

2002 14 40 26 7 8 95

2003 18 40 27 10 22 117

2004 16 48 31 11 10 4 120

2005 1 3 5 1 3 13CENTRE TOTAL 96 188 203 59 48 7 601

Patient recruitment was not evenPatient recruitment was not even

5/28 Australian surgeons did not recruit5/28 Australian surgeons did not recruit

2 Sth Aus surgeons entered 156 patients2 Sth Aus surgeons entered 156 patients 2 Q’land surgeons entered 147 patients2 Q’land surgeons entered 147 patients 2 NZ surgeons entered 81 patients2 NZ surgeons entered 81 patients

6 surgeons = 384 23 surgeons = 2106 surgeons = 384 23 surgeons = 210

Publications CommitteePublications Committee

New ZealandNew Zealand Randall AllardyceRandall Allardyce Phil BagshawPhil Bagshaw Frank FrizelleFrank Frizelle Chris FramptonChris Frampton Shona SmithShona Smith

AustraliaAustralia Peter HewettPeter Hewett Nick RiegerNick Rieger Michael SolomonMichael Solomon Andrew StevensonAndrew Stevenson

Points for considerationPoints for consideration

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

ALCCaS will conclude with 592 ALCCaS will conclude with 592 patients in March 2010patients in March 2010