1. T Staging: Rectal cancer T1 invades submucosa T2 invades muscularis propria T3 invades subserosa or perirectal tissues T4 invades peritoneum, organs or structures (15% of cases)

2. T4: Female

3. T4: Rectal cancer

7. Prostatic Involvement

8. T4: Male

10. Anterior T4 Rectal cancer APR + Radical prostatectomy

11. APR + Radical Prostate

12. T4: Posterior Rectal cancer

13. T4 Strategy: Staging  EUA, cystoscopy  MR pelvis  CT abdo, thorax  ? PET scan

14. T4 Strategy: Adjuvant therapy  RTH  Chemo/RTH  Intra op RTH  HIPEC: Hyperthermic Intra Peritoneal CT

15.  Pre-operative RTH plays a major role  Only a minority will be cured with RTH alone  Pre-operative CRTH has increased risks  Phase II studies oxaliplatin, irinotecan and capecitabine  What do we do with complete regression? Adjuvant Rx for fixed tumours

16. Current optimum CRT schedule Radiotherapy with 3 or 4 field plan 45 Gy in 25 # over 5 weeks Capecitabine 825mg/m2 bd for 5 weeks

17.  Stomas  Stenting  Nephrostomies T4 Strategy: Pre-emptive surgery

18. T4 Strategy: Definitive surgery  Engage the team  Stent the ureters  En bloc resection  ? IP Chemotherapy (peritoneal reflection)

19. Total Pelvic Clearance Christie NHST 2001 -2005 MDT Assessment Consecutive patients 100 Total Pelvic Clearance 45 Unsuitable for surgery 55

20. TPC: Surgical candidates Nutrition Renal function Liver function ? Disease confined to pelvis

21. Outcome of radical surgery  Primary v recurrent disease  Munro v mountain  30 - 80% 5y survival Lenhert et al 2002, Sanfilippo et al 2001, Law et al 2000

22. Total Pelvic Clearance n mortality morbidity % % Adachi et al 199990% 44% Kakuda et al 2003225% 68% Jimenez et al 2003555.5% 40+% Nakafusa et al2004530% 49% Sharma et al 2005484.2% 75% Sagar et al 2005181.6% na Christie 2006450% 11% op 38% non op

23. Christie: Total Pelvic Clearance Operative Stoma Revision2 Perineal wound 2 SBO1 Complications Non operative Infections12 PE/DVT1/1 Bleeding1 MI1 CVA1

24. Christie: Total Pelvic Clearance Age Number

25. T4 Tumours: HIPEC  Peritoneal involvement  Complete excision  Intraperitoneal mitomycin C 3 bolus over 90min @ 41- 43°C

26. Peritoneal metastasis

27. T4 : Palliative therapies  CRT  Pain relief  Tumour ablation  Tumour resection  Drainage of sepsis  Stenting and stomas

28. Survival: Cyto + HIPEC

31. T Staging: Rectal cancer T4 Male Invading adjacent organs

32. T4: Rectal cancer

34. Anterior T4 rectal tumour APR + Radical Prostate

36. Survival: Cytoreduction + HIPEC CRC Peritoneal v liver resections CRC complete CRC incomplete

37. T4 : Palliative therapies  CRT  Pain relief  Tumour ablation  Tumour resection  Drainage of sepsis  Stenting and stomas

38. What of it! She would have died anyway without the operation. There you are gentleman, you’ve seen the operation that everyone said was impossible, performed with complete success. But Doctor, the patient’s dead! T4: Palliative surgery

39. Survival: Cyto + HIPEC

40. Total Pelvic Clearance

41. Peritoneal carcinomatosis Sugarbaker

42. Survival with Colorectal Liver Metastases % years Scheele 1993

46. Surgical candidates Nutrition Renal function Liver function Proximal small bowel loops Disease confined to pelvis, R/LIF +/- omentum

47. T4 adjuvant IORT Fixed / inoperable tumours RTH + resection N = 248 Local recurrence free survival 11% RTH + resection + IORT N = 78 Local recurrence free survival 2.6% Sadahiro et al Dis Colon Rectum 2001

48. RTH for fixed rectal tumours 45 - 65% have potentially curable resections after radiotherapy 50% develop local recurrence Only a minority will be cured with RTH alone (Martenson et al, in Cancer of the colon, rectum and anus 1995)

49. Pre-operative CRT (Videtic et al, 1998)  Small studies n = 7-64  5FU, FA, cisplatin, mmc  RTh 40Gy/20#, 50Gy/30#  Resectability 70 -100%  Pathology T0 4 -72%  DFS 60 -80%

50. Preoperative RTH + Raltitrexed (tomudex) ASCO 2003 Fixed / inoperable tumours Christie and Walsgrave N = 36 MR T3: 17 T4: 19 Response: 81% Curative resection:64% Path T0: 14%

51. T4 Strategy: Pre-emptive surgery  Stenting  Stomas  Nephrostomies

52. HIPEC

54. Vaginal vault recurrence

55. Metastatic disease

56. Advanced disease