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W. Douglas Wong, M.D. Chief,Colorectal Service Memorial Sloan Kettering Cancer Center Professor of Surgery Cornell Univ PowerPoint Presentation
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W. Douglas Wong, M.D. Chief,Colorectal Service Memorial Sloan Kettering Cancer Center Professor of Surgery Cornell Univ

W. Douglas Wong, M.D. Chief,Colorectal Service Memorial Sloan Kettering Cancer Center Professor of Surgery Cornell Univ

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W. Douglas Wong, M.D. Chief,Colorectal Service Memorial Sloan Kettering Cancer Center Professor of Surgery Cornell Univ

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  1. Local Excision for Early Rectal Cancer - A Compromise Treatment 4th East – West Colorectal Days Hungary Oct. 16-18, 2008 W. Douglas Wong, M.D. Chief,Colorectal Service Memorial Sloan Kettering Cancer Center Professor of Surgery Cornell University Medical School

  2. Why the Controversy ContinuesPertinent Questions • Is local excision adequate therapy? • Which lesions are optimal for local excision? • Can we accurately stage early lesions? • Does adjuvant therapy improve the results? • Is salvage surgery effective for local failure?

  3. Local Excision for Rectal Cancer • Low morbidity/mortality • Eliminates radical resection • No colostomy • Excellent functional results • Unknown regional LN status • Adequate cancer treatment?

  4. Adequacy of Local Excision T1 T2 No. F/U LR Surv LR Surv UCSF 1999 32 5y 5% 95% 46% 83% Emory/MGH 1999 52 5y 11% 80% 66% 33% U of Minn 2000 101 5y 18% 72% 47% 65% MSKCC 2002 125 6y 14% 92% 28% 87% Gopaul 2004 53 2.5y 27% 83% _ _ Madbouly 2004 52 4.6y 29 75% _ _

  5. MSKCC Results of Local Excision125 pts 5-year % 10-year % Paty et al Ann Surg 2002

  6. Pattern of Recurrence(at first clinical failure) Allno RTRT Local 17 13 4 Local + distant 6 4 2 Distant 11 6 5 % with local 68% 74% 55%

  7. Salvage therapy for first recurrence N Resected NED Local only 17 14 (82%) 6 Local + distant 6 0 0 Distant only 11 3 (27%) 1 Total 34 17 (50%) 7 Median follow up of 7 survivors: 4.4 years, (0.7 - 20.3)

  8. DOD after LR salvage Survival after local excision p < 0.002

  9. Local Excision • The recurrence rate after local excision of T1 and T2 rectal cancers is substantial. • The majority of initial recurrences are local, implicating inadequate resection in treatment failure. • In this study, 28% of cancer deaths occurred beyond 5 years, raising concern that long-term cancer mortality may be higher than generally appreciated. • Only ½ of recurrences were resectable and less that half of these patients were salvaged

  10. Garrett M. Nash, Martin R. Weiser, Jose G. Guillem, Larissa K. Temple, Jinru Shia, Mithat Gonen, W. Douglas Wong, Philip B. Paty ASCRS 2008 Long-term survival after trans-anal excision vs radical resection for T1 rectal cancer

  11. Surgical treatment of rectal cancer TAE for T1 rectal cancer • Role of TAE • low and mid rectal cancers • uT1/2 • high risk surgical patients

  12. Surgical treatment of rectal cancer TAE for T1 rectal cancer • Disadvantages of TAE for T1 RC • Does not address lymph node disease • 15% LNM prevalence1 • Higher local recurrence Okabe S. J Gastrointest Surg. 2004 Dec;8(8):1032-9

  13. Local recurrence: TAE vs RR for T1 TAE for T1 rectal cancer 1. Mellgren A, Dis Colon Rectum. 2000;43:1064-71 2. Madbouly KM, Dis Colon Rectum. 2005;48:711-9 3. Bentrem DJ, Ann Surg. 2005;242:472-7

  14. Survival: TAE vs RR for T1 TAE for T1 rectal cancer 1. Mellgren A, Dis Colon Rectum. 2000 Aug;43(8):1064-71 2. Bentrem DJ, Ann Surg. 2005 Oct;242(4):472-7

  15. Study Aims TAE for T1 rectal cancer • Evaluate long-term recurrence and survival after surgical management of T1 rectal cancer • Identify risk factors for recurrence after TAE

  16. Hypothesis TAE for T1 rectal cancer • Trans-anal excision is an inferior cancer operation for T1 rectal cancer • Higher risk of local recurrence • Lower survival

  17. Patients TAE for T1 rectal cancer • Low and mid-rectal T1 cancer (2-12 from AV) • No neoadjuvant therapy • 282 cases, 1987-2005 • 137 TAE, 128 LAR, 17 APR • No perioperative deaths • Median follow up 5.5 years (0.3-16.3) • 23 LR, Median time to LR 2 years (0.5-8) • 23 DR, Median time to DR 2 years (0.3-8.8)

  18. Patient and Tumor Characteristics TAE for T1 rectal cancer

  19. Local Recurrence TAE for T1 rectal cancer

  20. Local Recurrence RR LRFS TAE p < 0.001 146 84 28 2 0 136 53 10 0 0 TAE for T1 rectal cancer

  21. Disease Specific Survival TAE for T1 rectal cancer RR TAE p = 0.02 146 86 29 2 0 136 65 13 2 0

  22. Overall survival TAE for T1 rectal cancer P = 0.03 RR TAE 145 85 29 2 0 137 56 14 2 0

  23. Recurrence in TAE TAE for T1 rectal cancer * P = 0.02

  24. Summary: T1 rectal cancer TAE for T1 rectal cancer • Up to 20% LNM prevalence • Patients selected for TAE are older (64 vs 59) • Tumors are more distal (6 vs 8cm) and smaller (2 vs 3cm) • Increased risk of local recurrence (HR 6.3) • Decreased DSS (87 vs 96%, at 5 years) • 46% of patients with recurrence had well/mod differentiated, small tumors with no LVI or PNI • Long term survival after recurrence is poor (31%)

  25. Conclusion TAE for T1 rectal cancer Tumor characteristics are inadequate to identify “high risk” tumors • TAE should be used selectively in T1 rectal cancer for patients considered to be at high risk for a major abdominal operation • Intensive, prolonged follow-up is necessary

  26. Local Excision • Clearly, most patients can be cured by local excision and avoid significant morbidity and potential mortality and avoid compromised bowel function • However, local recurrence rates are significant and the potential for salvage is diminished, and long term survival is less than following radical resection Can we identify patients who are at minimal risk for recurrence following local excision?

  27. Local Excision Unfortunately, the criteria for selection of patients for local excision are NOT well defined

  28. Local ExcisionCriteria for consideration • uT1 NO • well to mod. differentiated • 3cm or less • exophytic • absence of LVI or BVI • Accessible • Absence of clinical or radiologic evidence of lymph node involvement

  29. Local Excision Risk of Lymph Node Mets • Significant incidence variability in prior studies • Potential cause of eventual local recurrence • Multiple potential factors may influence lymph node status

  30. Potential Factors in Selection of Patients for Local Excision • Depth of invasion • Location • Morphology • Histopathology • Staging • Depth of wall • Nodal status • Age and co-morbidity • Molecular markers

  31. Potential Factors in Selection of Patients for Local Excision • Depth of invasion • Location • Morphology • Histopathology • Staging • Depth of wall • Nodal status • Age and co-morbidity • Molecular markers

  32. Incidence of Lymph Node Metastasis Based on Depth of Invasion Depth of Invasion LN mets (%) T1 0 – 12% T2 12 – 28% T3 36 – 79% Sharma et al Surg Oncol 2003

  33. Incidence of Lymph Node Metastasis T1 Lesions # pts LN mets (%) Minsky 168 0% Huddy 454 11% Billingham ( 5 studies) 761 12% Blumberg 48 10% Nascimbeni 353 13%

  34. Risk of Lymph Node Metastasis in T1 Rectal Ca Depth of Invasion into the Submucosa: sm1 = upper-third sm2 = middle-third sm3 = lower-third R. Nascimbeni, MD; L.J. Burgart, MD; S. Nivatvongs, MD; D. R. Larson, MS Dis Colon Rectum, February 2002

  35. Sm Level and Risk of LNM in T1 Rectal Ca R. Nascimbeni, MD; L.J. Burgart, MD; S. Nivatvongs, MD; D. R. Larson, MS Dis Colon Rectum, February 2002

  36. Potential Factors in Selection of Patients for Local Excision • Depth of invasion • Location • Morphology • Histopathology • Staging • Depth of wall • Nodal status • Age and co-morbidity • Molecular markers

  37. LN Metastasis in T1 Colorectal Cancer RIGHT 3% COLON (3 / 92) LEFT 8% COLON (13 / 160) RECTUM 15% (27 / 176) MSKCC Study Okabe et al, J GI Surgery 2004;8:1032-1040.

  38. Risk of LNM in T1 Rectal Ca R. Nascimbeni, MD; L.J. Burgart, MD; S. Nivatvongs, MD; D. R. Larson, MS Dis Colon Rectum, February 2002

  39. Potential Factors in Selection of Patients for Local Excision • Depth of invasion • Location • Morphology • Histopathology • Staging • Depth of wall • Nodal status • Age and co-morbidity • Molecular markers

  40. Morphology Criteria • Polypoid versus ulcerated • Mobile • Less than one third of circumference of the rectal wall • 3 cm or less in diameter

  41. Potential Factors in Selection of Patients for Local Excision • Depth of invasion • Location • Morphology • Histopathology • Staging • Depth of wall • Nodal status • Age and co-morbidity • Molecular markers

  42. LVI and Risk of LNM in T1 Rectal Ca R. Nascimbeni, MD; L.J. Burgart, MD; S. Nivatvongs, MD; D. R. Larson, MS Dis Colon Rectum, February 2002

  43. Histopathology MSKCC data (318 pts T1 and T2) LN mets Well or mod differentiated 14% Poorly differentiated 30% Lymphatic vessel invasion –ve 14% Lymphatic vessel invasion +ve 33% Blood vessel invasion –ve 13% Blood vessel invasion +ve 33% Blumberg et al DCR 1999

  44. Histopathology MSKCC data (318 pts T1 and T2) LN mets No adverse pathologic features 11% (Low risk group) Adverse pathologic features 31% (High risk group) Low risk T1 lesions 7% Blumberg et al DCR 1999

  45. Potential Factors in Selection of Patients for Local Excision • Depth of invasion • Location • Morphology • Histopathology • Staging • Depth of wall • Nodal status • Age and co-morbidity • Molecular markers

  46. Can We Accurately Stage Rectal Cancers Pre-Operatively?

  47. Modalities • Digital Rectal Exam • Rectal Ultrasound • CT • MRI

  48. Endorectal MRI Coil

  49. MRI

  50. MR Imaging (Phased Array) • Recent meta-analysis (Tjandra ANZ J Surg 2006) • Overall T staging accuracy 76% • T1 56% T2 52% T3 85% T4 83% • Overall N staging accuracy 69% • Major advantage is the assessment of the circumferential margin status