Minimally Invasive Surgery for Rectal Cancer Long Term Results John H Marks MD Chief Section of Colon and Rectal Surgery Main Line Health System

Speakers Disclosures Covideon- educational grant support, consultant, speakers bureau Wolfe- consultant, speakers bureau Stryker- consultant, speakers bureau Glaxo Smith Kline- consultant Zassi- consultant, honoraria Surgiquest- Scientific Advisory Board Adolor- speakers bureau

Section of Colon and Rectal Surgery Main Line Health System Lankenau Hospital and Lankenau Institute For Medical Research Wynnewood, PA

Lap Rectal Surgery The Learning Curve- Laparoscopic Colorectal Surgery

Morris Franklin MD- Franklin ME Jr. LAPAROSCOPIC COLON RESECTION (LETTER). Surgical Laparoscopy, Endoscopy &Percutaneous Techniques. 1992; 2(2):183 Phillips EH, Franklin ME, Carrol BJ, Fallas MJ, Ramos R, Rosenthal D: LAPAROSCOPIC COLECTOMY. Annals of Surgery. 1992 Dec 216(6):703-707

Advocates for Open Colon Surgery

Rectal Cancer TME Surgery?

Can we do Lap TME?

Top Questions Rectal Cancer Therapy Radiation Chemotherapy Surgery Short Course Radiation? Post-op? Bolus? Preop? r Agents? Laparoscopy???? Selective? High Dose? Not Needed? TME

TME

Laparoscopic Rectal Cancer Med-Line Review 1991-2008 164 articles 3 randomized controlled trials (individual) N=17 vs. 17 (Leung 2000) N=203 vs. 200 (Leung 2004) N=82 vs. 89 (Zhou 2004) 1 meta-analysis 1 Cochrane analysis CLASICC Trial- waiting

Laparoscopic Rectal Cancer Med-Line Review 2009-2010 2009- 50 articles (10 Review articles: 20%) 2010- 11 articles 7 original series 4 review articles (36%) No New Prospective Studies CLASICC Trial- waiting

Laparoscopic Rectal Cancer Level 1A Evidence =

Laparoscopic Rectal Cancer Will we ever have Level I A evidence? Is it needed? How address hierarchy of questions for rectal cancer?

Lap Rectal Cancer Studies Author Resection Year Design Lap Open Mean F/U (mo) Tsang LAR 2006 PNR 105 -- 26.9 Kim LAR/APR 257 30 Morino 2005 98 93 46.3/49.7 Barlehner 194 46 Dulcucq 218 57 CLASICC PR 253 128 3/3 Bretagnol 144 18 Leung 2004 203 200 52.7/49.2 Zhou 82 89 Breukink 25 Wu 2003 Leroy 102 36 100 45.7 2002

APR RATES Open Laparoscopic 27% 25% MRC CLASICC Trial Guillou PJ et al. Lancet 2005;365:1718-1726

Laparoscopic Conversion Rate Overall Conversion Rates MRC CLASICC Trial Laparoscopic Conversion Rate Overall 34% Year 1- 38% Year 6- 16% Guillou PJ et al. Lancet 2005;365:1718-1726

Positive Circumferential Margins R-0 Resection Rates MRC CLASICC Trial Positive Circumferential Margins Open- 14% Laparoscopic- 16% Guillou PJ et al. Lancet 2005;365:1718-1726

Laparoscopic vs. Open Total Mesorectal Excision for Rectal Cancer (Cochrane Review) Breukink S, Pierie J, Wiggers T; The Cochrane Collaboration 2007

Type of Studies Grade 1b (individual randomised trial) – 3 Grade 2b (individual cohort study) – 12 Grade 3b (individual case-control study) – 5 Grade 4 (case-series) – 28 Breukink S, Pierie J, Wiggers T; The Cochrane Collaboration 2007

Mortality No Difference Level 1b evidence (3 studies) No difference between lap vs. open Level 2b evidence (13 studies) Mortality 0-2.5% Level 3b evidence (2 studies) Mortality 0% in both groups Level 4 evidence (19 studies) Mortality 0-25%; 25% due to one study with only 4 patients of whom 1 patient died Breukink S, Pierie J, Wiggers T; 2007; The Cochrane Collaboration

Morbidity No Difference level 1b evidence (3 studies) 6.1% to 29% for the lap group and 12.4% to 35% for the open group 1 study found significant difference between lap and open group (6.1% vs. 12.4%; p=0.016) Level 2b evidence (9 studies) 20% to 37.6% morbidity 1 study did not find any significant difference between the two groups (p=0.26) Level 3b evidence (1 study) No significant difference between lap vs. open (p=0.26) Level 4 evidence (3 studies) 2 of the studies found significantly less morbidity in the lap group and 1 did not find a difference Breukink S, Pierie J, Wiggers T; 2007; The Cochrane Collaboration

Blood Loss Less in Laparoscopy No Transfusion Difference Level 1b evidence (3 studies) 2 of the studies found significantly less blood loss in the open group compared to the lap group Level 2b evidence (3 studies) 56 to 436 ml blood loss in the lap group Level 3b evidence (1 study) Found less blood in lap group compared to open group (250 vs. 1000ml; p<0.001) Level 4 evidence (3 studies) 2 of the studies found significantly less blood loss in the lap group Breukink S, Pierie J, Wiggers T; The Cochrane Collaboration 2007

Distal Margins R-0 Resections Lymph Nodes Lap group = Open group Pathology Distal Margins R-0 Resections Lymph Nodes Lap group = Open group Breukink S, Pierie J, Wiggers T; The Cochrane Collaboration 2007

3-Year and 5-Year Disease-Free Survival Rates No Difference level 1b evidence (1 study) 5-year disease-free survival rate of 75.3% in the lap group and 78.3% in the open group level 2b evidence (5 studies) 3 studies reported 67-88% survival rate of 5 years in lap 2 studies reported 63-75% survival rate of 5 years in lap level 3b evidence (1 study) 92% survival rate of 3 years in both lap and open group level 4 evidence (2 studies) 62.5-92.1% survival rate of 5 years in lap Breukink S, Pierie J, Wiggers T; The Cochrane Collaboration 2007

No Difference Local Recurrence level 1b evidence (1 study) 6.6% local recurrence rate in the lap group and 4.1% in the open group with a follow-up of 52.7 vs. 49.2 months level 2b evidence (8 studies) 3.75% to 6.8% local recurrence reported between 16 and 45.7 months level 3b evidence (4 studies) 0% to 6% local recurrence; no significant difference level 4 evidence (17 studies) 0% to 24.1% local recurrence 5 studies compared recurrence rate between the two groups and found no significant difference Breukink S, Pierie J, Wiggers T; The Cochrane Collaboration 2007

Postoperative Course The postoperative period of laparoscopic surgery offers the most benefits compared to open surgery There is evidence that laparoscopy results in an earlier return of normal diet, less pain, less narcotic use, and shorter hospital stay

Conclusion No immediate differences in oncological outcomes Less blood loss with laparoscopy Clinically measurable short-term advantages in lap group vs. open group Breukink S, Pierie J, Wiggers T; The Cochrane Collaboration 2007

Hand-assisted lap surg 58 (56.3%) Lap surg 45 (43.7%) Long-term outcomes of patients undergoing curative laparoscopic surgery for mid and low rectal cancer Dis Colon Rectum. 2009 Jul;52(7):1215-22 1999-2006 N=185 total Lap Rectal N=103 mid to low cancers Hand-assisted lap surg 58 (56.3%) Lap surg 45 (43.7%) Milsom JW, de Oliveira O Jr, Trencheva KI, Pandey S, Lee SW, Sonoda T

Results R0 resection rate= 100% Mean follow-up time 42.1 months Conversion rate was 2.9% R0 resection rate= 100% The anastomotic leak rate was 7.8% (n = 8). No 30-day mortality LR= 5% at five years. Overall survival was 91% Disease-free survival was 73.1% Milsom JW, de Oliveira O Jr, Trencheva KI, Pandey S, Lee SW, Sonoda T

CONCLUSION: Laparoscopic surgical techniques for mid and low rectal cancer seem safe and feasible with acceptable oncologic and long-term outcomes. Further studies, comparing laparoscopic and open methods, are warranted. Milsom JW, de Oliveira O Jr, Trencheva KI, Pandey S, Lee SW, Sonoda T

Laparoscopic versus open surgery for rectal cancer: long-term oncologic results Ann Surg. 2009 Jul;250(1):54-61 Assess long-term oncologic outcome after laparoscopic versus open surgery for rectal cancer and to evaluate the impact of conversion Two Periods of time: 1994-1999= Open N= 233 2000-2006= Lap N= 238 Laurent C, Leblanc F, Wütrich P, Scheffler M, Rullier E

Results: Lap Open Pvalue Mortality 0.8% 2.6%; 0.17 Morbidity 22.7% 20.2%; 0.51 R0 Resection 92.0% 94.8% 0.22 Laurent C, Leblanc F, Wütrich P, Scheffler M, Rullier E

Results: Lap Open Pvalue At 5 years: Local recurrence 3.9% 5.5% 0.371 Cancer-free survival 82% 79% 0.52 Conversion=15% no negative impact mortality, local recurrence, and survival Laurent C, Leblanc F, Wütrich P, Scheffler M, Rullier E

CONCLUSIONS The efficacy of laparoscopic surgery in a team specialized in rectal excision for cancer (open and laparoscopic surgery) is suggested with similar long-term local control and cancer-free survival than open surgery Moreover, conversion had no negative impact on survival. Laurent C, Leblanc F, Wütrich P, Scheffler M, Rullier E

after Chemoradiation Therapy Laparoscopic TATA Transanal-Abdominal-Transanal Radical Proctosigmoidectomy with Coloanal Anastomosis after Chemoradiation Therapy For Rectal Cancer Distal 3cm Thank you for the priveledge of presenting our data on laparoscopic TATA , a sphincter preserving technique for cancers in the distal 3cm of the rectum that would otherwise require an APR John Marks, Gerald Marks, Ben Mizrahi Section of Colorectal Surgery The Lankenau Hospital and Institute for Medical Research Wynnewood, PA

Goals Rectal Cancer Management Reduce local recurrence Increase survival Maintain normal function Avoiding a permanent colostomy Goals of rectal cancer management are controlling the cancer and maintaining QOL 38

Materials & Methods Prospective rectal cancer database since 1976 Prospective laparoscopic database since 1996 (N=1089) 102 patients treated with laparoscopic TATA All TME Inclusion criteria: Curative surgery Mobile tumors in the distal 3cm following neoadjuvant therapy 79 patients for study Using a prospective rectal cancer database and a prospective laparoscopic database, we identified 102 patients that were treated by laparoscopic TATA. Of these, 79 patients were eligible for the study 39

Pretreatment Tumor Characteristics Methods Level in rectum from anorectal ring: < 3.0 cm = 100% Mean = 1.2cm(-0.5-3.0cm) All tumors were in distal 3 cm of the rectum and 30% were below the 1 cm level <1cm: 30%

Laparoscopic TME Completion Rate Results Conversion to Open = 2.5% N=2 Only 2 patients were converted Surg Endo: Accepted for Publication

Morbidity and Mortality Results No Mortalities Minor Morbidities 18.9% Major Morbidities 11% Immediate: 2 failed anastomosis requiring stoma Delayed 4 full-thickness rectal prolapse with repair 1 ischemic neorectum with successful reanastomosis 2 bowel obstructions There were no perioperative mortalities And major morbidity rate of 11%

Operative Data Mean EBL: 367cc Positive distal margin: N=1 (1.2%) Results Mean EBL: 367cc Positive distal margin: N=1 (1.2%) BMI: 26.5 (17.4 - 47.5) # of Trocars: 3: 9 (11%) 4: 47 (60%) 5: 19 (24%) 6: 2 (3%) Mean estimated blood loss was 367cc And even with BMIs up to 47

TATA: Transanal Portion

Lifetime normal sphincter function: 90% Stoma Rate N=79 Results Lifetime normal sphincter function: 90% Neorectal loss due to: 2 + margins 2 failed anastomosis 2 were not reversed due to comorbidities 1 stoma secondary to bowel obstruction 1 recurrence 90% of patients lived their life without a permament colostomy *All had temporary diverting ostomy following TATA

Oncologic Outcomes Local Recurrence: 2.5% KM5YAS: 97% Results Local Recurrence: 2.5% KM5YAS: 97% Distant Metastasis: 10.1% Our local recurrence rate is a surprisingly LOW 2.5% (PAUSE) Five year survival is 97% Surg Endo: Accepted for Publication

Comparison of outcome of open and laparoscopic resection for stage II and stage III rectal cancer Ann Surg Oncol. 2009 Jun;16(6):1488-93. Epub 2009 Mar 17 Law WL, Poon JT, Fan JK, Lo SH. Department of Surgery, University of Hong Kong Medical Centre Compare survival of patients laparoscopic and open resection for stage II and III rectal cancer Open resection: n = 310 Laparoscopic resection: n = 111 June 2000 to December 2006

Results: No Diferrence: Lap Better: Age, gender, medical morbidities, ASA class, type of operation, morbidity, mortality, pathologic staging Lap Better: Blood loss, length of stay Law WL, Poon JT, Fan JK, Lo SH. Department of Surgery, University of Hong Kong Medical Centre

Cancer Results: Median follow-up = 34 months No difference in local recurrence rates 5-year actuarial survivals were: 71.1% in the laparoscopic 59.3% open groups (P = .029) Law WL, Poon JT, Fan JK, Lo SH. Department of Surgery, University of Hong Kong Medical Centre

Cancer Results: Multivariate analysis: Better survival: laparoscopic resection (P = .03, hazards ratio: 0.558, 95% confidence interval: 0.339-0.969). Poor prognostic factors: Lymph node metastasis poor differentiation perineural invasion postop complications no chemotherapy Law WL, Poon JT, Fan JK, Lo SH. Department of Surgery, University of Hong Kong Medical Centre

CONCLUSIONS: Laparoscopic resection for locally advanced rectal cancer is associated with more favorable overall survival when compared with open resection Law WL, Poon JT, Fan JK, Lo SH. Department of Surgery, University of Hong Kong Medical Centre

Randomized Clinical Trial Comparing Laparoscopic and Open Surgery Future Prospective trials and long-term follow-up are needed COLOR II Randomized Clinical Trial Comparing Laparoscopic and Open Surgery For Rectal Cancer

Future Prospective trials and long-term follow-up are needed

ACOSOG Z6051- Lap vs Open Rectal Resection

ACOSOG Z6051- Lap vs Open Rectal Resection Accrual Goal= 480 240 each arm Endpoints: Circumferential margins > 1mm Distal margin > 2cm, > 1 cm distal rectum Complete TME

“If there is no struggle, there is no progress!” Frederick Douglas (1817-1895)

Airplane Problem or Pilot Problem???

Conclusions: ACOSOG trial will put this question to rest Technically can certainly be done No reports show anything worse laparoscopically Better short term outcomes: Pain EBL