1. Dr Mark Saunders Christie Hospital and Paterson Institute of Cancer Research “ Rectal cancer radiotherapy – why do we give it and how do we do it?”

2. Pre or post-operative radiotherapy ? “potentially” operable tumours (“fixed”) Pre-operative (long course of CRT) Operable tumours (“mobile” or “tethered”) Pre-operative (short course of RT or long course of CRT) Post-operative (long course of CRT*) (* CRM < 1mm, High risk of residual disease, Perforation, fistulae)

3. Operable tumours

4. “Early” surgery v surgery + RT studies Pre-op :Higgins et al(75, 86) Rider et al(77) MRC working party(84) Post-op :GITSG(86) Balslev et al(86) Fisher et al (88) ALL :No difference in local control or survival

5. “Later” surgery v surgery + RT studies Pre-op :Cedermark et al(90) Gerard et al(88) Goldberg et al(94) MRC CRO2(96) Post-op :MRC CRO3(96) ALL :Significantly improved local control. Survival unchanged.

6. MRC CRO2 study (1996) Surgery v surgery + pre-op RT. 40 Gy / 20 fractions (A/P 18 x 15 cm). Surgery 4 weeks later. 279 patients RT :Smaller tumours which were down-staged. At 5 years :Surgery :46 % local recurrence. Surgery + RT :36 % local recurrence. (p = 0.04) No survival advantage. No significant difference in operative complications.

7. MRC CRO3 study (1996) Surgery v surgery + post-op RT. 40 Gy / 20 fractions (A/P 18 x 15 cm). RT 4 - 6 weeks later. 469 patients. At 5 years :Surgery :34 % local recurrence. Surgery + RT :21 % local recurrence. (p = 0.001) No survival advantage.

8. The “English” study (1994) Northwest rectal cancer group. Tethered or fixed tumours. 284 patients Surgery v surgery + pre-op RT. 20 Gy / 4 # (10 x 10 x10 rotation field). Operate within one week of completing RT RT group - Reduced LR (36.5 v 12.8%, p=0.0001). Recurrences - 10 inside, 6 outside RT field. No difference in survival…..but, survival advantage in patients undergoing “curative” surgery (45.6 - 53.3%; P=0.03) (Marsh, James and Schofield, Dis colon rectum, 1994)

9. 1168 patients Surgery v surgery after pre-op RT (25Gy / 5 fractions) Local recurrence : 27 v 11 % (p<0.001) Overall survival : 48 v 58 % (p=0.004) Benefits to all Dukes stages (NEJM 336; 980-7, 1997) The “Swedish” study (1997)

10. The “Dutch” study (2001) 1861 patients. Operable rectal cancer. TME + RT (25 Gy in 5 fractions). Local recurrence at 2 years. TME:8.2% TME + RT:2.8% (p<0.001) No survival benefit (Kapiteijn et al, NEJM, 345 (9), 638-646, 2001)

11. Recurrence and distance from anal verge TMERT/TME 10 - 15cm3.8% 1.3% 5 - 10cm10.1% 1.0% < 5cm10.0% 5.8% (At 2 years) (Kapiteijn et al, NEJM, 345 (9), 638-646, 2001)

12. Anterior resection :20 - 30 %1990 + Pre-op RT (25/5) :10 % (Swedish) TME : <10 % + Pre-op RT (25/5) : < 5 % (Dutch) 2000 Local recurrence after surgery and radiotherapy for rectal cancer

13. MERCURY group Evaluating the use of MRI and selected use of pre-operative radiotherapy for rectal cancers No radiotherapy if tumour > 5mm from mesorectal sheath “Radiology guided” Where next….many trials, including:

14. How do we do it?

15. First of all, we get the patient in the correct position

27. What are our results?

28. 171 pts under the care of NAS at Hope Hospital 11 years (1992 – 2003) 88 patients had 20Gy/4f RT then curative surgery Median FU: 5.16 years 5 yr survival : Dukes A 96%, Dukes B 65% and Dukes C 36%. 4 recurrences in lesser pelvis or perineal wound NW: 20 Gy in 4 fractions pre-op RT

29. LR : 4.2 % at 3 years (Dutch 2.8% at 2 yrs (TME + RT) Conc’n: Our proven rate of LR is acceptable and we would suggest caution when increasing the dose / volume / chemotherapy / treatment complexity given the good survival of this group of patients and their risk of long-term side-effects

30. Thank you