1. Radical surgery is the preferable treatment option for T1- 2/N0 low rectal cancer Jose G. Guillem, MD, MPH Department of Surgery Memorial Sloan Kettering Cancer Center Great Debates & Updates in GI Malignancies March 28-29, 2014

2. Rectal Cancer Surgical Options Local Recurrence T 1 N 0 18%0% T 2 N 0 47%6% Mellgren et al. Dis Colon Rectum, 2000

4. Inadequacy of baseline ERUS staging of primary and LN disease StagePooled Sensitivity (%) Pooled Specificity (%) T187.898.3 T280.595.6 T396.490.6 T495.498.3 N+ (overall)73.275.8 N+ (2001-2008)70.978.6 Puli SR et al. Ann Surg Oncol.. 2009 *Meta-analysis N = 2732 cases

5. Evaluated parameters Sensitivity (%)Specificity (%)Diagnostic Odds Ratio (%) T stage877520.4 MRF involvement779456.1 LN involvement77718.3 Inadequacy of baseline MRI staging of primary, MRF, and LN involvement *Meta-analysis N = 1249 cases Al-Sukhni E et al. Ann Surg Oncol. 2012

6. 6.4mm5.7mm ERUS Identification of N1 Disease Photomicrograph (x20, H&E) of a lymph node that is 70% replaced by tumor.

7. Micrometastatic Disease Photomicrograph (x20, H&E) of a lymph node with a 1mm tumor deposit

8. ERUS Lymph Node Staging is T Dependent StagenpN+ Median metastasis size (mm) ERUS Nodal Accuracy Specificity pT1216 (29%)0.34867 pT26720 30%)4.16775 pT34420 46%)5.98483 pT421 (50%)3.0100 All1347 (35%)4.97076 Landman, et al Dis Col Rectum (2007)

9. TAE for T1 Rectal Cancer 1. High risk of ca recurrence vs. RAD. 2. TAE has a lower cancer cure rate. 3. Neither adjuvant therapy nor surgical salvage are reliable. Paty P et al Ann Surg 2002 Bentran D et al Ann Surg, 2005 Nash, G DCR, 2008

10. Survival outcome of local excision versus radical resection of colon or rectal carcinoma: a surveillance, epidemiology, and end results (SEER) population-based study N = 13,262 pts with rectal cancer Surgery –3715 (28%) local excision –9547 (72%) major resection Preoperative clinical T staging –953 (7%) Tis –6223 (47%) T1 –6086 (46%) T2 Bhangu A et al. Annals of Surg. 2013.

11. Survival outcome of local excision versus radical resection of colon or rectal carcinoma: a surveillance, epidemiology, and end results (SEER) population-based study Bhangu A et al. Annals of Surg. 2013. LEMajor resection Adjusted HRp value Tis OS CSS 76.% 95.1% 79% 96.2% 1.05 0.78 0.777 0.494 T1 OS CSS 71.8% 92.3% 80.6% 94.4% 1.29 1.16 <0.001 0.236 T2 OS CSS 63.1% 85.2% 75.6% 91.5% 1.38 1.71 <0.001 *Estimated 5y OS and CSS

12. Local excision in early rectal cancer – outcome worse than expected: a population based study N = 3694 consecutive stage I rectal ca pts from Swedish Rectal Cancer Register 448 LE vs 3246 radical resection (Hartmann, LAR, APR) LE pts –LR 11.2% (vs ~3% for all radical procedures combined) –Relative survival 0.81 (95% CI 0.75-0.88) Saraste D et al. Eur J Surg Oncol. 2013.

13. Multimodality salvage of recurrent disease after local excision for rectal cancer You YN et al. Dis Colon Rectum. 2012. 5y OS s/p salvage 63% 3y RFS s/p salvage 43% In salvage surgery R0 resection in 80%, Multivisceral 30%, neoadjuvant 70% Sphincter preservation in 33%

14. Salvage resection after local excision for rectal cancer Study, yearInitial surgery Initial stageSalvage surgery of curative intent, n Rate of R0 resection, % Rate of sphincter preservatio n, % Long-term (5-y) outcome, % MD Anderson, 2002 LET1, T2297934DFS 59 MSKCC, 2005 LET1, T2509730DFS 53 The Netherlands, 2010 TEMS protocol T1169456DSS (3-y) 58 Rome, 2012TEMS protocol T1, T2, T32688.543OS 62 MD Anderson 2012 LET1, T2, T3408032OS 68; RFS (3-y) 43

15. Predicting lymph node metastases in early rectal cancer N = 677 pts with pT1-2 rectal Ca in the Swedish Rectal Cancer Register Saraste D et al. Eur J Cancer. 2013. Multivariate analysis OR 95% CI (Ref 1) T21.97(1.19-3.25) Poor differentiation6.47(2.71-15.4) Vascular infiltration4.34(2.46-7.65)

16. Predicting lymph node metastases in early rectal cancer Saraste D et al. Eur J Cancer. 2013.

17. Preoperative Considerations if Pursuing a Sphincter Preserving Resection Determination is both preop and intraop Body habitus, sphincter mass? Sphincter tone, squeeze? Co-morbidities? Patient expectations, enthusiasm? Understands the “good news/bad news” post operative scenario.

18. As in fly fishing…“Match the Hatch” “Match the Disease” Should be the governing paradigm in the management of rectal cancer J Guillem, Ann Surg 2007