Laparoscopic Surgery for Colorectal Carcinoma Evidence to date Ilmo Kellokumpu M.D., Ph.D. Central Hospital of Central Finland
Laparoscopic Surgery for Cancer: Historical, Theoretical, and Technical Considerations Potential applications for minimally invasive surgery exploded during the 1990s - cancer surgery Due to early reports of tumor dissemination and port-site metastases progress stalled leading to a period of virtual moratorium: associations were drawn between CO2 pneumoperitoneum and wound recurrence Furthermore, oncologic surgical training was relatively devoid of instructors familiar with minimally invasive methods
Laparoscopic colorectal surgery Minimally invasive (high tech) revolution Barcelona 2002, Honkong 2003, COST 2004, CLASICC 2005, COLOR I 2005, LAPKON II 2009, AUSTRALASIAN STUDY 2012 Short-term benefits Medium- to long-term oncologic equivalence Potential for reduction in late morbidity
Colon carcinoma Treatment options (location, number, genetic background) Segmental colectomies Right Left Transverse Extended R/L Sigmoid Subtotal/total colectomy Extended resections Small bowell Abdominal wall Duodenum/pancreas Ureters Uterus, ovaries Bladder 10%-multivisceral en bloc resection Role of laparoscopy?
Laparoscopic segmental colectomy for colon carcinoma Surgery of the planes Advantages better visibility and ease of dissection magnification of dissection planes reduced ileus, pain and hospital stay Disadvantages technically demanding long learning curve increased operative time case selection (CTadjacent organ invasion) better cosmesis
Major randomized trials Trial Assigned Group No. of Patients Conversion Rate (%) Operative Time (min) Estimated Blood Loss (ml) Lymph Node Count COST 7 Lap 437 21 150 12 Open 435 95 12 CLASICC 8 COLOR I 10 Lap 273 29 180 12 Open 140 135 14 Lap 621 17 145 100 10 Open 627 115 175 10 ALCCaS 9 Lap 298 15 158 100 13 Open 294 107 100 13
Surgical outcome Trial Assigned Group No. of Patients Time to 1st BM (d) Hospital Stay (d) 30-d Morbidity (%) 30-d or In- Hospital Mortality (%) COST 7 Lap 437 3 5 21 0.5 Open 435 4 6 20 0.9 CLASICC 8 COLOR I 10 Lap 273 5 9 26 4 Open 140 6 9 27 5 Lap 621 3.6 8 21 1 Open 627 4.6 9 20 2 ALCCaS 9 Lap 298 4 10 38 1.4 Open 294 5 11 45 0.7
Similar recurrence and survival rates Trial Assigned Group No. of Pts Recurren ce (%) Port-Site Recurren ce (%) DFS (%) OS (%) COST 7 16 Lap 437 19 0.9 69 76 Open 435 22 0.5 68 76 CLASICC 17 COLOR I 15 ALCCaS 14 Lap 273 11 2.4 58 56 Open 140 9 0.5 64 63 Lap 621 1.3 b 74 b 82 b Open 627 0.4 76 84 Lap 298 14 72 78 Open 294 15 72 76 b 3 year
Laparoscopic vs open colectomy for colon cancer: oncologic safety Transatlantic laparoscopically assisted vs Open colectomy trials study group Arch Surg 2007; 13: 413-424 (meta-analysis) Barcelona 2002 RCT COST 2004 RCT CLASICC 2005 RCT COLOR 2005 RCT (44 institutions in Europe and 48 in USA, total 1536 pts) Inclusion criteria: curative surgery before March 1, 2000, complete 3 years FU, Lap 796 pts, Open 740 pts Exclusion criteria : past colon surgery, distant mets, intestinal obstruction, adjacent organ invasion, ca of transverse colon
Transatlantic laparoscopically assisted vs open colectomy trials study group. Arch Surg 2007; 13: 413-424 (meta-analysis) Barcelona 2002, COST 2004, CLASICC 2005, COLOR 2005 (44 institutions in Europe and 48 in USA, total 1536 pts) 90 80 70 60 50 40 30 20 10 0 82,283,5 75,575,3 19 1,4 1,6 30d mort 3yr OS 3yr DFS C-version Fig are % Lap Open LN lap 11.8 vs open 12.2 Resection margin+ lap 1.3% vs open 2.1% Level 1 evidence now exist to support the equivalence of laparoscopic approach to the standard open approach
Evidence in favor of laparoscopy Cochrane Database of Systematic Reviews 2009 Lap fundo > medical therapy- intermed. term 2008 Lap IPAA vs open IPAA - better cosmesis 2008 Lap colorectal cancer = open - long term results 2006 Lap CBDE=ERCP for CBD stones, less procedures 2006 Lap chole > Open chole short term benefits 2005 Lap colorectal > Open - short term benefits 1987 Lap Chole (Mouret)
Summary Colon carcinoma Level 1 evidence from major RCTs shows that laparoscopic-assisted surgery for colon cancer is as effective as open surgery and produces similar long-term outcomes Comparable resections Longer op.time, less bleeding Faster recovery Less stress reaction, better preserved immunity Long term survival no difference QoL favour laparoscopy (social functioning) Hospital/health care costs favour open Schwenk et al. Cochrane Database Syst. Rev. 2005 Oct 18;(4): CD003145 Breukink et al. Cochrane Database Syst rev 2006, Oct 18;(4): CD005200 Aziz et al. Ann Surg Oncol 2008;17(3):519-531(meta-analysis)
10 Days Are the outcomes optimal? Hospital stay after colonic surgery Honkong, COLOR, CLASICC (open and lap, 8-9d) 8 6 Standard Open 8d Barcelona COST Möiniche (1995) Liu (1995) Choi (1996) Bradshaw (1998) 4 2 Standard Lap 5d Senagore (2002) Senagore (2001) Bardram (2000) Bardram (1995) Smedh (2001) Di Fronzo (1999) Basse (2000) Kehlet (1999) 0 traditional care laparoscopic open, epidural + lap + Fast-track" Fast-track" open + Fast-track"
Fast-Track Care - The Second Revolution in Colorectal Surgery LAFA-trial: Ann Surg 2011 Laparoscopy, early mobilization and oral intake associated with shortened hospital stay. EnROL study: J Clin Oncol 2014 Lap rectum 5d vs open 6d, p=0.024 ERAS registry data: Ann Surg 2015 (1509 colon+843 rectum) Laparoscopy significantly reduced complications (OR =0.68) and hospital stay (OR=0.83)
Additive role of laparoscopy in the fast-track care own experience Faster recovery of oral diet, bowel function and shorter hospital stay Lower morbidity FT lap (n=73) FT open (n=43) Stand. lap (n=73) Stand. open (n=43) In-hospital mortality,n 0 0 0 1 NS Liquids >1l, median d 1 1 1 2 <0.001 Solid food, median d 2 2 3 4 <0.001 Flatus, median d 1 1 2 3 <0.001 Postop.stay,median d 3 4 5 7 <0.001 P
Impact of FT care on in-hospital costs Bootstrap type analysis of covariance Mean total cost/patient including index admission and readmissions 14 13 12 11 Fast-Track Standard Post-op. stay FT lap vs. ST. Lap: mean diff -2 days FT open vs. stand. Open: mean diff -3days Costs / 1000 10 9 8 7 6 5 4 3 Preoperative Operating room Postoperative 2 Fast-Track vs.standard 1 0 Lap. Open Lap. Open Fast-Track: Lap. vs Open Standard: Lap. vs Open ST Lap. vs. FT Lap. ST Open. vs. FT Lap. ST Lap. vs. FT Open ST Open. vs. FT Open Total costs, mean difference FT vs standard -1492e -5-4 -3-2 -1 0 1 2 3 4 5 Mean difference in Total Costs, 1000
Determinants of post-operative LOS Multivariate zero-truncated Poisson regression analysis using patient (age, sex, BMI, ASA), disease (benign vs. malignant)- and surgery-related variables LOS ratio 95%CI P FT vs. Standard care 1.56 1.39-1.74 <0.001 Lap vs. Open 1.17 1.04-1.33 0.009 Surgical morbidity 1.85 1.52-2.25 <0.001 General morbidity 1.73 1.38-2.15 <0.001 Dindo-Clavien gr. 1-2 vs. 3-5 1.89 1.55-2.31 <0.001
Variability in the quality of open surgery and long-term oncologic outcome West et al. JCO 2010;28:272-8 West et al. (Quirke) Lancet Oncology 2008; 9: 857-865 399 colon specimens: OS advantage at 5 years 15%, if mesocolic plane surgery
Complete mesocolic excision- Erlangen technique Hohenberger et al. SJS 2003, Hohenberger et al. Colorectal Dis 2009 Wide excision of tumour bearing colon segment along the embryological planes within complete mesenteric envelope (mesenteric LN) Central vascular ligation (apical LN) Resection of an adequate length of bowel (5-10cm, pericolic LN) Søndenaa et al. Int J Colorectal Dis (2014) 29:419 428 (Consensus conference)
Open vs Laparoscopic CME? Gouvas et al. Colorectal Disease 2012 Laparoscopic and open left- and right-sided specimens similar Transverse colon Open > Lap Longer length of central ligation to tumour (diff 3cm, p = 0.049) Longer length of central ligation to bowel wall (diff 2.5cm, p = 0.015) Better lymph node clearance (open 46 vs lap 39, p = 0.033).
Lap colon ca - own experience 5-year overall survival, n= 222, Stage I-IV Colon cancer - 5 year OS (n=222) 80.9%, Stage I-III (R0 n=210) 83.8% 5yr OS 80.1% P<0.001 120 OS% % 100 80 60 40 20 0 CHCF vs Erlangen 94,9 87,5 74,4 16,7 Stage I Stage II Stage III Stage IV
DFS by Stage I-III and tumour location Own experience 5-year DFS stage I-III (n=210) 85.8% 94.9% 91.1% 74.1% P=0.001 Stage P=0.001 Stage III Right 71.7% Transv/flexures 71.4% Left 77.4%% P=0.95
Laparoscopic Surgery for Rectal Carcinoma Multimodal management Surgery (TME) Oncology Anterior resection Intersphincteric resection Abdominoperineal resection Laparoscopic Robotic- Transanal TME Experimental (Local excision)x Preoperative RT 5x5Gy Preoperative CRT 45-50.4 Gy + 5FU / Capecitabine Adjuvant chemotherapy (Stage III/high risk stage II)
Low rectal cancer Classification and standardization of surgery Rullier et al. Dis Colon Rectum 2013; 56: 560-67 Supra-anal > 1 cm from the AR (>2cm DL) CAA Juxta-anal < 1 cm from the AR (<2cm DL) partial ISR Intra-anal - IS invasion total ISR Transanal - external sphincter/levator invasion Cylindrical APR
Defining treatment strategy Endoscopy, Bioprobe, ERUS, MRI, thoracoabdominal CT, +PET-CT 2 liver mets T4bN1M1 Good- surgery only ct1-t3a/b(<5mm)n0,mrf- Bad- 5x5 and surgery (next week) ct3c/d(>5mm)n0 upper, middle, ct3b low, T1-T3N+, MRF-,T4 peritoneum, vagina Ugly- CRT and surgery (6-8wks) ct3 MRF+, ct4b, lat. LN+ Tumour level, radiological TNM-estimate, T3-subclassification, distance to mesorectal fascia, EMVI, sphincter invasion, response to CRT
Laparoscopic TME for rectal carcinoma Advantages Disadvantages Better visibility Magnified view Easier identification of autonomic nerves Faster recovery Reduced morbidity? Difficulties in assessing T level and distal margin Lack of stapler angulation, multiple firings Costs Learning curve
Difficult cases Male patients, narrow pelvis, distal bulky tumours and obesity Hand-assisted ultralow anterior resection Hybrid surgery midline or Pfannenstiel incision, conventional staplers Conversion to open Transanal-TME TAMIS Experimental Rouanet et al. DCR 2013 for resection of difficult rectal tumours (n=30) Lacy SE 2013 flexible single port device and standard LAPinstruments
Laparoscopic rectal resection Randomized clinical trials Lap Open Surgery RT/CRT Araujo 2003 13 15 APR 100% vs. 100% Zhou 2004 82 89 LAR - CLASICC 2005, 2010 253 128 L/AR, APR 5.5% vs. 6.7% Gonzalez 2006 20 20 AR, APR 50% vs. 45% Braga 2007 83 85 AR, APR 17% vs. 14% Ng 2008 51 48 APR - Lujan 2009 101 103 LAR, APR 72% vs. 72% Ng 2009 (upper rectum) 76 77 AR - COREAN trial 2010 170 170 LAR, APR 100% vs. 100% Liang 2011 169 174 LAR, APR - COLOR II 2013 699 345 L/AR, APR 59% vs. 58%
Exclusion criteria for Lap in RCTs T4 T3 with margin < 2mm from the endopelvic fascia (COLOR II) Synchronous or metachronous colorectal cancer Metastatic (M1) disease Recurrent rectal cancer Intestinal obstruction or perforation IBD Contraindications to laparoscopy No informed consent Ref. Araujo 2003 1, Zhou 2004 2, CLASICC 2005 3, Gonzalez 4 Braga 2007 5, Ng 2008 6, Lujan 2009 7, Ng 2009 (upper rectum) 8, Kang 2010 9, Liang 2011 10, COLOR II 2013 11
Laparoscopic rectal resection CLASICC trial Guillou et al. Lancet 2005 - Lap 253 vs. Open 128 Conversion rate 34%, no differences in short-term endpoints Oncologic clearance similar Fig are % or n (days) LN harvest CRM+ rate All: CRM+ 16% vs.14% AR:CRM+ 12% vs.6% APR: CRM+ 20% vs.26%
Laparoscopic rectal resection COREAN trial Kang et al. Lancet Oncol 2010: Lap 170 vs. Open 170, Neoadj. CRT 100% - Conversion rate 1.2% 25 20 15 10 23,5 21,2 LAP Open Fig are % or n (days) 8 9 Oncologic clearance Oncologic similar clearance LN harvest Resection margins CRM+ 2.9% vs. 4.1% 5 0 0 0 Mort. Compl. Bowel function 1,6 2,5 3,53,9 Normal diet Hosp. stay Mesorectal plane surgery 72% vs. 75% <0.0001 <0.0001
Laparoscopic rectal resection COLOR II trial van der Pas et al. Lancet Oncol 2013: Lap 699 vs. Open 345 Neoadj. RT/CRT 60% - Conversion rate 17% Oncologic clearance Oncologic similar clearance Fig are % or n (days) LN harvest Resection margins CRM+ (<2mm) 10% (Low 9% vs. 22% p=0.014 ) Mesorectal plane surgery 88% vs. 92% <0.0001 <0.005 0.036
Intraoperative outcome RCTs Lap Open Ref. Longer op.time 9 / 11 120-262 min 106-284 min 2,3,5-10 Araujo- shorter Gonzalezsimilar Less bleeding 6 / 8 20-322 ml 92-556 ml 2,4,5,7,9,11 Intraop. complication CLASICC COLOR II 18% 12% 14% 14% Conversion rate variable: 1.2%-34% Ref. Araujo 2003 1, Zhou 2004 2, CLASICC 2005 3, Gonzalez 4 Braga 2007 5, Ng 2008 6, Lujan 2009 7, Ng 2009 (upper rectum) 8, Kang 2010 9, Liang 2011 10, COLOR II 2013 11
Postoperative recovery (Lap>Open) Faster return to oral intake Faster recovery of bowel function RCTs Lap (d) Open (d) Ref. 8 /10 2-6 2-6.3 4-11 7 / 8 1.5-5 2.5-6 2,4, 6, 8-11 3 Similar Less pain and analgesic use 4 / 5 6,8, 9,11 Gonzalez 2- no difference Faster mobilization 3 /3 3.5-4.4 4.1-5.9 6,8,10 Hospital stay: 1-2 days shorter in the laparoscopic group Ref. Araujo 2003 1, Zhou 2004 2, CLASICC 2005 3, Gonzalez 4 Braga 2007 5, Ng 2008 6, Lujan 2009 7, Ng 2009 (upper rectum) 8, Kang 2010 9, Liang 2011 10, COLOR II 2013 11
Similar 30-day mortality and morbidity RCTs Lap % Open % Ref. Mortality 11 / 11 0-4 0-5 1-11 Morbidity 9 / 10 6-45 12-52 3,4-11 Zhou 2: Lapless Anastomotic leak 9 / 9 0-13 0-12 2-5, 7-11 Wound infection 8 / 9 0-15 1.9-30 3-8,10,11 Kang 9: Lapless Ref. Araujo 2003 1, Zhou 2004 2, CLASICC 2005 3, Gonzalez 4 Braga 2007 5, Ng 2008 6, Lujan 2009 7, Ng 2009 (upper rectum) 8, Kang 2010 9, Liang 2011 10, COLOR II 2013 11
Similar oncologic quality of resection RCTs Lap Open Ref. LN no. 6 / 8 5.5-17.0 7.8-18.0 1,5-6, 8-10 Lujan & Gonzalez Lap > Resection margins similar similar CRM+ (%) 7 / 8 0-16 1.3-20 3-9, 11 Gonzalez 4-Open more CRM+ Mesorectal Plane (%) COREAN COLOR II 72 88 75 92 9,11 COLOR II: low rectal cancer CRM+ Lap 9% vs. Open 22% p=0.014 Ref. Araujo 2003 1, Zhou 2004 2, CLASICC 2005 3, Gonzalez 4 Braga 2007 5, Ng 2008 6, Lujan 2009 7, Ng 2009 (upper rectum) 8, Kang 2010 9, Liang 2011 10, COLOR II 2013 11
Laparoscopic rectal resection CLASICC trial Colon 5-year oncologic outcome similar Rectum
COREAN trial: 3-year survival outcomes of an open-label, non-inferiority RCT For locally advanced rectal cancer after preoperative CRT laparoscopy provides similar outcomes for DFS as open resection, thus justifying its use. 100 80 91,790,4 79,2 72,5 LAP Open 60 40 20 0 2,6 4,9 LR (AR) OS DFS Seung-Yong et al. Lancet Oncol 2014
COLOR II trial: 3-year survival outcomes Bonjer et al. N Engl Med 2015 Laparoscopy provides similar oncologic outcomes as open resection 90 80 70 60 50 40 30 20 10 0 86,7 83,6 74,8 70,8 5 5 LR (AR) OS DFS LAP Open
Long-term morbidity - Lap vs. Open Fewer long-term (5-10 years) complications after laparoscopic rectal resection: 6.3% vs. 17.2%, p=0.003braga & Ng % Bowel obstruction p=0.07 p=0.01 p=0.033 Cumulative first complication event, % 50 45 40 35 30 25 20 15 10 5 0 OPEN LAP HR = 1.40 (95% CI: 1.03 to 1.91) 0 12 24 36 48 60 72 84 96 Time, months
Long-term complications Late anastomotic complications (strictures, fistulas, sinus) Lap (%) Open (%) Ref. (Open) (%) 15.4 19.0 12.0-16.0 strictures 0.8-3.2 fistulas Incisional hernias (all sites) 6.7 11.8 9.4-11.6 Stomal complications (prolapse, parastomal hernia) Kellokumpu et al. Dis Colon Rectum 2012 2.7 9.4 13.4-37.0 Perineal wound problems 0 15.0 16.0-20.0 CRT Bowel obstruction 3.7 6.9 2.5-7.0 Nonreversal of stoma after LAR 1.6 7.5 17.0-19.0 Radiotherapy: Cardiovascular and thrombotic events, secondary primary tumours
Are the autonomic pelvic nerves better preserved? Sexual dysfunction Bladder dysfunction 19-69% Ho et al. 2011 15-50% Delacroix & Winters 2010 worse SF (IIEF) after Lap Quah 2002 RCT trend towards worse SF (IIEF) in men, QLQ-CR38 sexual variables similar Jayne 2005 RCT no difference Liu 2009 RCT, KangRCT2010 similar urinary function at 3 months Jayne 2007 RCT fewer micturition problems at 3 months after lap Kang et a. 2010 RCT
Quality of life (EORTC QLQ-30 and CR38) CLASICC trial 2007 No difference at 2 weeks, 3 months and 3 years COLOR II 2013 No difference at 4 weeks, 6 and 12 months COREAN trial 2010 Lap > Open at 3 months: better physical functioning, less fatique, less micturition, GI- and defecation symptoms Male sexual problems similar
Laparoscopic rectal resection In-hospital costs similar Higher operating room costs, lower hospitalization costs Pounds Euros USD Franks et al. (CLASICC) Br J Cancer 2006 Lap 222, Open 118 Gonzalez et al. Int J Colorectal Dis 2006 Lap 20, Open 20 Ng et al. Ann Surg Oncol 2008 Lap APR 51, Open APR 48 NS NS p<0.001 Braga et al. DCR 2007 351 USD extra cost per Lap patient
Laparoscopic resection for rectal cancer Conclusion Level 1 evidence remains to be proven by European Color II, COREAN, US ACSOG-Z6051 and Japanese JCOG 0404 trials Feasible and safe in the multimodal setting (selected patients) Less bleeding, faster recovery (oral nutrition, bowel function, pain, mobilization) and shorter hospital stay Similar mortality, morbidity and quality of life, potential for reduction in late morbidity Lap offers similar radical resection for noninvasive rectal cancer - similar long-term oncologic outcome Meta-analysis Trastulli 2012 (9 RCTs)
Large population-based studies Everyday surgical practice Decreased 30-day morbidity, reduced length of stay Similar oncologic quality of surgery Rectal cancer, USA ACS NSQIP 2005-2009, 237 hospitals 4380 open, 1040 lap, Greenblatt et al. J Am Coll Surg 2011 Rectal cancer, PROCARE (Belgium) 2006-2011, 82 hospitals 1896 open, 764 lap, Penninckx et al. Br J Surg 2013 Colorectal ca, Netherlands 2010 4986 colon, 2364 rectal ca, Kolfschoten et al. Ann Surg 2013 Colorectal ca, English NHS 2006-2008 47180 open, 10955 lap, Taylor et al Arch Surg 2012
New technical and oncosurgical challenges 3D - NIR-fluoresence- Robotic 3-D NIR