1. Management of early rectal carcinoma Joint Hospital Surgical Grand Round Jeren Lim United Christian Hospital

2. Early rectal carcinoma Adenocarcinoma invaded into, but not beyond the submucosa T1N0M0 tumour 3 – 8.6% of all resected rectal carcinomas Tytherleigh et al, Br J Surg 2008; 95: 409-423

3. Treatment Radical surgery ◦ Total mesorectal excision (TME) ◦ Abdominoperineal resection (APR) Local excision (full thickness) ◦ Transanal endoscopic microsurgery (TEM) ◦ Transanal endoscopic operation (TEO) ◦ Others: Transanal excision

4. TEM Full thickness excision 1cm resection margin Tumours at 6-15cm from anal verge Sharma et al, Surg Oncol 2003; 12: 51-61 Karita et al, Gastrointest Endosc 1991; 37: 128-132

5. TEM advantages vs radical surgery Less major postoperative complications (RR 0.16, P<0.0001) Lower perioperative mortality (RR 0.15, P=0.03) Avoids need for stoma (RR 0.11, P<0.00001) Kidane et al, Dis Colon Rectum 2015; 58: 122-140

6. TEM advantages vs radical surgery Lower blood loss (P<0.001) Shorter operative time (103 vs 149mins, P<0.05) Shorter hospital stay (5.7 vs 15.4 days, P<0.0001) Kunitake et al, Perm J 2012; 16: 45-50

7. TEO Modification of TEM High definition 2D TFT monitor Standard universal laparoscopic instruments

8. TEO vs TEM Less steep learning curve Relatively shorter surgical time Lower overall costs (€2031 vs €2603, P=0.003) Nieuwenhuis et al, Surg Endosc 2009; 23: 80-86 Serra-Aracil et al, World J Gastroenterol 2014; 20: 11538-11545

9. Question How effective is local excision in terms of oncological control?

10. Local excision vs radical surgery A nationwide cohort study National Cancer Database of American College of Surgeons T1 rectal cancers Higher 5-year local recurrence rate (12.5% vs 6.9%, P<0.003) Lower 5-year disease specific survival rate (93.2% vs 97.2%, P=0.004) You et al, Ann Surg 2007; 245: 726-733

11. TEM vs radical surgery Systemic review and meta-analysis Compared oncological control T1N0M0 rectal adenocarcinoma 1 randomized controlled trial and 12 observational studies 2855 patients Kidane et al, Dis Colon Rectum 2015; 58: 122-140

12. TEM vs radical surgery 5-year local recurrence Kidane et al, Dis Colon Rectum 2015; 58: 122-140

13. TEM vs radical surgery 5-year overall survival Kidane et al, Dis Colon Rectum 2015; 58: 122-140

14. Question How to select the suitable patients for local excision?

15. Management controversy Local excision does not remove the mesorectum and regional LN Problem of predicting the N (nodal) staging in T1 tumours Tytherleigh et al, Br J Surg 2008; 95: 409-423

16. Lymph node metastasis T1 tumours: 0-12% T2 tumours: 12-28% T3 tumours: 36-79% Chang et al, J Surg Educ 2008; 65(1): 67-72

17. Preoperative locoregional staging Endorectal ultrasound (ERUS) ◦ T-staging accuracy: 69-97% ◦ N-staging accuracy: 61-80% Klessen et al, Eur Radiol 2007; 17: 379-389

18. Preoperative locoregional staging Magnetic resonance imaging (MRI) ◦ T-staging accuracy: 67-86% ◦ N-staging accuracy: 57-85% Klessen et al, Eur Radiol 2007; 17: 379-389

19. Preoperative locoregional staging Difficult for MRI to differentiate between T1 and T2 tumours. ERUS is more valuable for T-staging Combination of ERUS and MRI is useful for N-staging Mulla et al, Indian J Radiol Imaging 2010; 20: 118-121 Muthusamy et al, Clin Cancer Res 2007; 13: 6877-6884

20. Preoperative staging No imaging modality can completely rule out mesorectal nodal involvement Thus pathological examination after local excision is necessary Categorize T1 tumours into low or high risk Iafrate et al, Radiographics 2006; 26: 701-714

21. Haggitt classification Tytherleigh et al, Br J Surg 2008; 95: 409-423

22. Kikuchi classification Kikuchi et al, Dis Colon Rectum 1995; 38: 1286-1295 0-3.2%8-11%12-25% Lymph node metastasis

23. Histopathological features of T1 tumours Low riskHigh risk DifferentiationWell, moderatePoor Haggitt level1-3- Kikuchi levelSm1, +/- Sm2Sm3, +/- Sm2 Lymphatic or vascular invasion NoYes Resection margin involvement NoYes Tytherleigh et al, Br J Surg 2008; 95: 409-423

24. Low risk vs high risk Long term results from the Memorial Sloan-Kettering Cancer Center Paty et al, Ann Surg 2002; 236: 522-529 Disease specific survival

25. Immediate salvage surgery High risk T1 tumours No compromise in outcome when performed immediately after local excision 30-day mortality (P=0.49) Local recurrence (P=0.49) Distant metastasis (P=0.61) Levic et al, Tech Coloproctol 2013; 17: 397-403

26. Local recurrence Salvage surgery Outcomes are inferior to those who initially received radical surgery Only 59% were disease free at a mean follow-up of 39 months after salvage surgery Friel et al, Dis Colon Rectum 2002; 45: 875-879

27. Question Is there a role for adjuvant therapy?

28. Adjuvant therapy Local excision for T1 and T2 tumours With and without RT Chakravarti et al, Ann Surg 1999; 230: 49-54 5-year actuarial local control

29. Adjuvant therapy Local excision + RT + chemotherapy T1 and T2 cancers 5-year local control rates increased from 81% to 96% Not significant (P=0.15) Chakravarti et al, Ann Surg 1999; 230: 49-54

30. Adjuvant therapy Systemic review of 11 studies Local excision with chemoRT in T1 and T2 cancers Local recurrence 10% Overall survival 75% Disease specific survival 89% Ung et al, Colorectal Dis 2014; 16: 502-515

31. NCCN guidelines 2015 Early rectal carcinoma High risk pT1, NX T2, NX Low risk pT1, NX ERUS, MRI cT1, N0 (Size <3cm, <30% bowel circumference, mobile) Local excision Salvage surgerySurveillance

32. Conclusion TEM has a comparable overall survival rate to radical surgery in T1N0M0 rectal cancers Higher local recurrence rate Patient selection is important Imaging and histopathological features help to predict lymph node metastases

33. Conclusion Full thickness local excision by TEM / TEO is suitable for low risk T1 rectal carcinomas Immediate salvage surgery recommended if high risk features present Adjuvant therapy showed no significant benefit in T1 cancers

34. Thank you