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. Rectal Cancer: TME Circumferential resection margins determine outcome

3. T4 Treatment failure Poor Judgement Inadequate skills Lack of knowledge Lack of insight/arrogance Inadequate resources Common condition Uncommon variant Higher order of treatment

4. T4: Female

5. T4 Male anterior tumours

6. T4 Rectovesical peritoneum

7. T4 Seminal vesicles T4 Male Invading adjacent organs

8. T4 Seminal vesicles T4 Male Invading adjacent organs

9. Anterior T4 prostatic involvement APR + Radical prostatectomy

10. APR + Radical Prostate

11. T4 Bladder involvement

12. T4: Male anterior tumours

14. T4: Posterior Rectal cancer

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

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

17. Current CRT schedule Radiotherapy with 3 or 4 field plan 45 Gy in 25 # over 5 weeks Capecitabine 825mg/m 2 bd for 5 weeks

18. CRT for fixed rectal tumours 45 - 65% have potentially curable resections after CRT When is the right time to operate? 10-12 weeks post DXT

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

20. TPC: Surgical candidates Nutrition Renal function Liver function ? Disease confined to pelvis Re assess clinically and radiologically after CRT

21. Total Pelvic Clearance Christie NHS FT 2001 -2005 MDT Assessment pre and post CRT Consecutive patients 100 Total Pelvic Clearance 45 Unsuitable for surgery 55

22. Christie: Total Pelvic Clearance Age Number

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

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

25. Total Pelvic Clearance n mortality morbidity % % 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 2008510% 11% op 38% non op

26. Christie: Total Pelvic Clearance Operative Stoma Revision3 Perineal wound 2 Bleeding1 SBO1 Complications Non operative Infections12 Ileus10 PE/DVT1/1 Bleeding1 MI1 CVA1

27. Advanced/Recurrent Pelvic tumours 0 20 40 60 80 100 % 012243648 Time (months) Colorectal Others (57%) (31%) Cancer-specific survival CRM +ve 9%

28. Perineal reconstruction Gracilis

29. TRAM Flap Perineal reconstruction

30. Tissue interposition Omentum

31. 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

32. T4 Tumours: HIPEC Intraperitoneal mitomycin C 3 bolus over 90min @ 41- 43°C

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