GRECCAR 1 prospective muticentric randomised trial

1. Sphincter preserving surgery after preoperative treatment for ultra-low rectal carcinoma. A French multicenter prospective trial: GRECCAR 1 P Rouanet, M Rivoire, B Lelong, E Rullier, L Vanseymortier, L Mineur, P Lasser, M Pocard, JC Ollier, JL Faucheron, F Dravet, D Pezet, JM Fabre, J Balosso, C Lemanski, S Gourgou, B Saint Aubert. GRECCAR (French surgical research group of rectal carcinoma).

2. GRECCAR 1prospective muticentric randomised trial Inclusion: LRC which requires APR TIP - LA < 2 cm / UT2-T3 HDR (45 Gy + 18 Gy) LRC R Surg CT if pN+ RCT (45 Gy + 5FU continuous) PA : Incidence of conservative surgery SA : - Oncological and functional results - Down staging impact on survival - Quality of life

3. CISR PISR M ISR complete ISR partial Mucosectomy Classification of Anoproctectomy Based on : - mucosal resection - endoanal resection Intersphincteric Resection

4. Ano-Proctectomy Mucosectomy Partial ISR Complete ISR

5. 80 40 70 35 60 30 50 25 40 HDR 20 RCT 30 15 20 10 10 5 0 0 VA CLB 2001 IPC StA 2002 COL CSC 2003 IGR CRG CPS Gren CF Mtpl CAV 2005 2004 GRECCAR 1 : inclusion curves 4/2001 – 4/2005 : 207 patients in 13 centers

6. Effectives n: 100 n: 96

7. Patient characteristics Results at 23 months Data base ended Feb 06 *median

8. Tumor characteristics RE Colo USR *Median in centimetres

9. RE USR Evaluation of neoadjuvant treatments *Median in centimetres

10. Treatment toxicities Grade 3-4 HDR RCT • Peri anal Dermititis 75% 44% p : 0.21 • Diarrhea 53% 40% p : 0.51 • Prostatitis 25% 20% p : 0.74 • Nausea 4% 8% p : 0.49 • Cystitis 18% 28% p : 0.34 • Failure to continue TTT 7% 0 average 5 d (2-15)

11. 72% Surgery: Conservative rate 85%

12. TIP-LA Cons rate 0 very low 76 84% ≤ 2 cm low 120 84% Incidence of Conservation in relation to Topography

13. Incidence and distribution of APR by center

14. Operative morbidity • According to pre op TTT HDR RCT Fistula 9% 3% p : 0.13 Pelvic abscess 2% 4 % p : 0.40 Colonic necrosis 3% 3% p : 0.99 Anastomotic stenosis 5% 4% p : 0.75 • According to type of surgery APR M P ISR C ISR Fistula 1 (3%) 4 (19%) 4 (6.9%) 2 (2.6%) p:0.06 Pelvic abscess 1 (3%) 2 (9.5%) 1 (1.7%) 2 (2.6%)p:0.36 Colonic necrosis 1 (3%) 0 2 (3.5%) 1 (1.3%) p:0.09 Anastomotic stenosis 0 2 (9.5%) 6 (10.3%) 1 (1.3%) p:0.06

15. Anatomical pathology *median

16. RO Patients : 78% Classical R1 patients n: 44 22% • CRM • = 0 n: 4 3 APR 1st, 1 APR 2nd • <1 n: 9 9 AP 1st , 1 APR 2nd • = 1 n : 29 • DM • = 0 n : 2 2 AP 1st , 1 APR 2nd "Real" R1 patients n: 15 7.6% ?

17. Relation between pT and pN staging pN+ => pT0-pT1 : 2/38 – 5.2% , pT2: 19/67 – 28% , pT3-4: 53/91 – 59%

18. Oncologic results HDR RCT 2-year OS 93% 95% p: 0.69 2-year DFS 78% 76% p: 0.70 2-year LR 6% 5% p: 0.94 2-year Mt 17% 21% p: 0.53 Stoma closure 90% 94%p: 0.40 Median FU : 23 months

19. Overall survival

20. Survival according to the type of surgery

21. Survival without local relapse

22. Preliminary conclusions of GRECCAR 1 • 85% of sphincter conservation in respect with the oncological quality criteria. • No significant statistical difference between HDR and RCT arms • Possible standardization of the surgery: the crucial impact of the surgical technique (72% of ISR). • Tumoral Down staging is an excellent prognostic factor : It can modify an initial surgical indication of APR into conservative surgery. • More follow-up is needed in order to analyse the oncological safety and the functional reliability of this treatment.