1. RT with TME surgery ? OUTLINEOUTLINE

2. Prostate Seminal vessels Neurovascular bundle Denonvilliers Fascia “holy plane” (Fascia rectalis) Total Mesorectal Excision - TME

3. Local Failure at 5 years: RT+TME: 5.6% TME: 10.9% p < 0.001 Kapiteijn E et al.,N Engl J Med 2001;345: 638-46 Peeters K et al., Ann Surg 2007;246:693-701 TME-Trial: RT + TME vs. TME

4. (Kapiteijn E et al, N Engl J Med 2001, Peeters et al., Ann Surg 2007 ) RT+TME TME alone Local recurrence: UICC-Stage I 0,5/ 0,4%0,7/ 1,7% n. s. UICC-Stage II 1/ 5,3%5,7/ 7,2% p=,01/ p=0,33 UICC-Stage III 4,3/ 10,6%15/ 20,6% p<0,001/ p<0,001 2-y/5-y Preoperative Radiotherapy Combined with Total Mesorectal Excision for resectable rectal cancer

5. RT+TME TME alone Local recurrence: Tumor 0-5 cm5,8/ 10,7%10/ 12% p=0,04/ p=0,6 Tumor 5-10 cm1,0/ 3,7%10,1/ 14% p<,0001/ p<0,001 Tumor 10-15 cm1,3/ 3,7%3,8/ 6,2% p=0,17/ p=0,12 2-y/5-y (Kapiteijn E et al, N Engl J Med 2001, Peeters et al., Ann Surg 2007 )

6. Risk reduction at 5y < 2y Only stage III benefited from RT However: subgroup analyses ! „Caution is warrented not to irradiate stage I/II“ RT associated with late toxicity Risk-Adapted RT/CRT ? … Lessons to be learned from the Dutch trial

7. 5x5Gy +TME TME+RCT if CRM+ MRC-CR07MRC-CR07 3-year Results Preop. RT + TME (n=674) TME + RCT if CRM + (n=676) Hazard- Ratio (95%CI) Local Recurrence 4.7%11.1% 2.5 (1.61-3.79) Disease-free Survival 79.5%74.9% 1.31 (1.02-1.67) Overall Survival 80.8%78.7% 1.25 (0.98-1.59) ? Sebag-Montefiore D et al., J Clin Oncol 2006; 24(18S): 3511

8. Local Relapse Rate at 3y TME- Quality NPreop. RT + TME OP + RCT if CRM + Hazard- Ratio “Poor”: Defects in Muscularis propria 141 (13%) 9%29% 2.8 “Moderate”: Intra-mesorectal Excision 382 (34%) 6%12% 2.0 “Good”: Mesorectal Excision 596 (53%) 1%6% 4.5 MRC-CR07MRC-CR07 Sebag-Montefiore D et al., J Clin Oncol 2006; 24(18S): 3511

9. RT with TME surgery? YES! But some subgroups may not benefit SUMMARYSUMMARY