1. Discrepant issues in the treatment of colon cancer
Eric Rullier
Deparment of Surgery
University Victor Segalen of Bordeaux
France
Moscow, April 5-6, 2012

2. Treatment of colon cancer
Staging
Surgical technique
Strategies
Adjuvant treatment

3. Discrepancies in Surgical Techniques
Colon cancer
Discrepancies in Surgical Techniques

5. 1329 patients 5-year survival% % %

6. Plane of dissection in
399 colonic specimens
, Leeds
Muscularis propria 24%
Intramesocolic 44%
Mesocolic 32%

7. Plane of dissection and type of colectomy

8. Complete Mesocolic Excision improves survival
All patients Stage III

9. How to explain the better results?

11. Complete Mesocolic Excision (CME)
Technical insufficiency issue
More frequent in right colectomy
Impact of extended lymphadenectomy vs. CME ?
Novel concept or standardization of an old technique !?

12. Discrepancies in modern surgical techniques
Colon cancer
Discrepancies in modern surgical techniques

13. First acceptation of laparoscopic colectomy 2004 US COST

14. Barcelona, COST, COLOR, CLASICC

15. International guidelines
Laparoscopic surgery is recommended for colon cancer US UK
France
Europe
Asia
Australia
…since 2005 !

16. Contradiction Patients excluded from trials
Obstruction, perforation
T4, size > 6 cm
Transverse, splenic flexure location
Polyposis, IBD
Previous laparotomy, BMI > 30
Surgeons excluded from trials
< 20 or 30 previous laparoscopic procedures
Leung Lancet 2004, COST NEJM 2004, COLOR Lancet Oncol 2005, CLASICC Lancet 2005

19. Reality: Colorectal Surgery in France 2010
National Database: PMSI
procedures
75% colon
25% rectum

20. Place of laparoscopy in colorectal surgery in France: 40%

21. Proportion of laparoscopy according to type of colectomy

22. Complexity and type of surgery
Difficulty score and surgical procedure
Colectomy
TME
Jamali FR et al. Arch Surg 2008

23. Impact of experience on conversion & mortality Evidence based
Converted Not converted
National trials
Mid experienced surgeons
CLASICC % 9% 1%
Single centers
High experienced surgeons
Braga DCR % 1% 1%
Luga BJS % 3% 2%

24. Perspectives for laparoscopic colectomy
Good indications
T1-T3NxMx colon cancer
Right & left location
Educated and experienced surgeon in laparoscopy and colorectal surgery
Relative indications
T4 colon cancer
Transverse location
BMI > 30
Expert lap surgeon with high volume of cases

25. Discrepancies in ultra modern surgical techniques
Colon cancer
Discrepancies in ultra modern surgical techniques

28. Robotic Surgery

29. Current status of robotic colorectal surgery
Two meta-analysis (Maeso S, Ann Surg 2010) (Mirnezami AH, Colorectal Dis2010)
Five controlled, non-randomized studies:
(Spinoglio G, 2008) (Woeste G, 2005) (D’Annibale A, 2004) (Anvari M, 2004) (Delaney CP, 2003)
focused on colorectal resection
included several diseases and surgical procedures
Feasibility and Safety (Maeso S, Ann Surg 2010)
Rob vs. Lap
Surgical procedure
Open conversion
↓ 4%
Blood loss NS
Morbidity
Quality of specimen resection
Resection margin
Lymph nodes

30. Preliminary conclusion of robotic surgery
Clinical advantages difficult to find in colorectal
Probably impossible without experience
At least 1 case a week necessary
Advantages must be point out
Patient: selected cases (obese, T4?)
Surgeon: less stess
Education: easier than laparoscopy
Institution: Marketing +++
Limitations
Lack of tactile and tensile feedback

31. Discrepant issues in surgical techniques
Complete Mesorectal Excision
New concept or standardization of surgery ?
Laparoscopic colorectal surgery
In selected patients for selected experienced surgeons
In all patients for high volume expert surgeons
Single Port and Robot
The futur or the past ?
Evidenced based is necessary

32. Discrepant strategies Advanced complicated disease
Colon cancer
Discrepant strategies
Advanced complicated disease

33. Large bowel obstruction
20% of patients with colon cancer presented with bowel obstruction
No recommandation for treatment
Surgical options
Colostomy then colectomy
Hartmann then redo anastomosis
Total colectomy
High morbidity & stoma rates
BJM

34. New option for obstruction: colonic stenting
International registry
182 patients
98% technical success
94% clinical success
Complications 8%
Perforation 3%
Migration 1%
Obstruction 3%
Bleeding 1%
Jimenez-Perez J et al. Am J Gastroenterol 2011 (Dec)

39. Multicenter French Colonic Stenting Trial
Stent Surgery
(n=30) (n=30)
Colostomy
Technical failure 16 (53%)
Perforation
Premature closure of the study (n=80)

41. No data about long term oncologic outcome
- perforation ?
- tumor compression ?

43. Colonic stenting: perspectives
New randomized trials ongoing (UK)
Better selection
Patient selection (M0 vs M1)
Tumour location (left colon vs rectum)
Impact on chemotherapy
Interval between stent & surgery
Design of the stent

44. Discrepant strategies Early colon cancer

45. Polypectomy vs. Colectomy in T1 colon cancer

46. Lymph node metastases in degenerated polyps
10-15%
27%
Hagitt et al

47. Risk factors of lymph node metastases in T1 colon cancer
7543 patients treated by colectomy for cancer
Incidence of T1= 8.6%
Rate of N+ = 13%
Predictive factors of N+
Sm3
Lymphovascular invasion
Poor differentiation
Nascimbeni R et al. Dis Colon Rectum 2002

48. Standard for colectomy in T1
Sm2 or Sm3
Lympho vascular invasion
Poor differentiation
Residual disease (margin < 1 mm)

49. What is new: balance strategy
Retrospective study 2000 to 2010
64 patients with colectomy for unfavorable histology
Definitions
Oncologic risk: rate of N+ or R1
Operative risk: severe complication grade III-IV or death
Aim : to analyse the correlation between the oncologic and the operative risks
Benizri EL Int J Colorectal Dis 2012

50. Balance strategy for T1 colon cancer
64 colectomies
Oncologic risk 11%
7.8% N+
3.1% R1
Operative risk 13%
12.5% grade III-IV
0 death
Oncologic benefit only if ≥ 2 histologic criteria
Benizri EL Int J Colorectal Dis 2012

51. Conclusion controversy for T1 colon cancer
Guidelines
Taking account the oncologic risk
Colectomy if 1 unfavorable histologic criteria
Reality
Taking account both the oncologic and the operative risks
Colectomy if 2 unfavorable histologic criteria ?

52. Discrepancies in adjuvant treatments
Colon cancer
Discrepancies in adjuvant treatments

53. New classification of colon cancers
TNM 7th edition (2009)

56. 43 032 patients with colon cancer stage II & III
Definition of stage II poor prognosis
Bowel obstruction
Bowel perforation
T4 stage
Lympho-vascular invasion

58. Stage II
Poor prognosis
Stage III

60. Adjuvant chemotherapy for colon cancer
Evidence based for Stage III (6 m Folfox)
Challenges for stage II
Risk-benefice ratio unfavorable in all stage II
Discrepant results in poor stage II
Futur: new markers: RER & genetic signatures
Challenges in old patients
Older than 75y or with comorbidities
Optimal CT : FU alone vs Folfox ?

62. FOXTROT UK trial

63. Coordonnateur : Pr Mehdi KAROUI (Chirurgien – Paris La Pitié)
PRODIGE 22 – ECKINOXE Phase II randomisée : chimiothérapie néo-adjuvante par FOLFOX-4 avec ou sans Cetuximab vs chirurgie d’emblée dans le cancer colique localement avancé n° Eudract: – N° promoteur: P Essai intergroupe: AERO, FFCD, UNICANCER, FRENCH, GRECCAR
Coordonnateur  : Pr Mehdi KAROUI (Chirurgien – Paris La Pitié) 63 v

64. STUDY DESIGN Randomisation stratifiée sur : centre investigateur64
STUDY DESIGN
15 jours
3 à 5 semaines 3 à 5 semaines
FOLFOX-4 (4 cures)
ARM A
Surgery
FOLFOX-4 (8 cures) R
FOLFOX-4 - cetuximab (8 cures)
FOLFOX-4 - cetuximab (4 cures)
Surgery
ARM B (KRAS non muté)
Surgery
FOLFOX-4 (12 cures)
ARM C
15 jours
Randomisation stratifiée sur :
centre investigateur
stade ctT (T1-2-3 vs T4) sur scanner initial
stade ctN (N0-N1 vs N2) sur scanner initial
Et selon le statut K-ras :
KRAS non muté (WT) : bras A, bras B, bras C
KRAS muté : bras A et C v

65. New perspectives in adjuvant chemotherapy for colon cancer
Neoadjuvant vs. adjuvant chemotherapy
Two national trials
Foxtrot UK trial
Echinoxe F trial

66. Discrepant issues in treatment of colon cancer Conclusion
CME: a new old concept = standardization
Laparoscopy: experienced and high volumes teams increase laparoscopic cases
Single port & Robot: a new challenge
Obstruction: stent only palliative cases
T1: apply guidelines but remember the patient
ChemoT: the futur is treatment before surgery