1. Management of Locally Advanced Rectal Cancer Joint Hospital Surgical Grand Round Pamela Youde Nethersole Eastern Hospital Dr. YH Ling 19 May 2007

2. Colorectal Cancer Primary modality of treatment: Surgical Resection

3. Rectal Cancer Middle and lower rectum –Located in the confined pelvis –Close relationship with urogenital tracts anal sphincters

4. Goal of treatment Achieve oncological cure –Radical resection Negative distal and circumferential margin

5. Goal of treatment Preserve –Urinary function –Sphincter function –Sexual function Maintain the quality of life

6. Radical resection Pelvic organ functions

7. Locally advanced rectal cancer Tumour and/or regional nodes have invaded the adjacent organs –Bladder, ureters –seminal vesicles, prostate –vagina –sacrum

8. Pre-op imaging and staging Surgery RadiotherapyChemotherapy

9.  Better local disease control  Improved overall survival  Greater sphincter preservation rate

10. Treatment of locally advanced rectal cancer Multidisciplinary cancer management Surgeons Oncologists Diagnostic radiologists

11. Locally advanced rectal cancer Pre-op staging Neoadjuvant chemoradiation therapy

12. Locally advanced rectal cancer

13. Tumour and/or regional nodes have invaded the adjacent organs –T3-4 or N+ –6-10% of rectal cancer

16. CRM ≤ 2mm distinguishes the TNM stage III patients with high risk of local recurrence (21.4%) from patients with lower risk of local recurrence (12%), p = 0.03

17. Locally advanced rectal cancer Tumour growing < 2mm from the mesorectal fascia (fascia proper) Beyond mesorectal fascia With major lymph node involvement

18. Pre-operative staging

20. Imaging modalities CT scan MRI –With or without endorectal coil Endorectal ultrasound

21. CT scan Widely used to stage colorectal cancer Not good for local staging –Cannot delineate layers of bowel wall microinvasion of perirectal fat –Cannot detect small lymph node metastases (<1cm) lymph nodes close to the tumour

22. Endorectal ultrasound (ERUS) Accuracy –T staging: 83% –N staging: 65-83% Kim NK, et al. Ann Surg Oncol 2000;7:732 – 7 Savides TJ, et al. Endosc2002;56(S4):S12 – 8.

23. Endorectal ultrasound (ERUS) Limitations: –Bowel wall penetration (T): Inflammatory peritumoral changes mimic deeper invasion  Overstage T2 tumour –Nodal status (N): Difficult to differentiate inflammatory and metastatic nodes Difficult to detect small or distant lymph nodes

24. Endorectal ultrasound (ERUS) Limitations: –Stenotic lesion Difficult to pass the transducer –Operator dependent –“ Sampling error ” for large tumour

25. MRI Advantage: –Visualize the distance between the tumor and the rectal fascia proper

26. MRI Limitation: –Inability to distinguish tumour extension from inflammatory changes –  overstage T2 lesions Brown G, et al.Br J Surg 2003;90:355 – 64 Vliegen RFA, et al.Imaging 2003;10 – 6 Williamson PR, et al. Dis Colon Rectum 1996;39:45 – 9 Fleshman JW, et al. Dis ColonRectum 1992;35:823 – 9

27. Preoperative staging of rectal cancer H. Kwok, LP Bissett, GL Hill et al Int J Colorectal Dis (2000) 15:9-20 Systemic review 83 studies from 78 papers 4897 patients

28. Bowel wall penetrationNodal status Acc (%)Sen (%)Spe (%)Acc (%)Sen (%)Spe (%) CT737863665278 ERUS879378747176 MRI828677746580 MRI with endorectal coil 84897982 83

29. MRI with endorectal coil Most useful technique for preoperative staging of rectal cancer Limited availability  Limits its routine use Limited use in stenotic lesions

30. Neoadjuvant chemoradiation therapy

31. Potential Advantages Reduction in tumour size –improve resectability –increase sphincter preservation Decrease risk of local failure –Improve tumour response in the pre- operative setting

32. Potential Advantages Decrease risk of toxicity –Small bowel more readily excluded from the radiation field in preoperative setting Less bowel dysfunction –Colon used for reconstruction is not in the radiation field No delay of therapy in patients with operative morbidity

33. Disadvantage: Over-treat patient with pre-op overstaged disease

34. Preoperative staging of rectal cancer H. Kwok, LP Bissett, GL Hill et al Int J Colorectal Dis (2000) 15:9-20 Staging modality Accuracy (%) Over- staged (%) Under- staged (%) CT80137 ERUS84115 MRI7413 MRI with endorectal coil 81126

35. Prospective randomized clinical trials that analyzed neoadjuvant therapy for rectal cancer StudyYearNMain results Swedish rectal cancer trial 1997908High-dose pre-op radiation therapy reduced local recurrence and improved survival Dutch colorectal cancer group 20011805Pre-op radiation therapy decreased local recurrence following total mesorectal excision German rectal cancer study group 2004823Pre-op chemoradiation therapy improved local control but did not improve overall survival compared to post-op chemoradiatoin therapy

37. Rectal cancer T3 or T4 or N + Long course radiation + Infusional 5-FU TME Radiation therapy + Infusional 5-FU n = 415n = 384 6 weeks

38. 5-year cumulative risk of local failure: –Pre-op chemoradiation group: 6% –Post-op chemoradiation group: 13% P = 0.006 Survival: –No difference in two groups

39. Improved sphincter preservation rates in pre-op chemoradiation therapy group

40. 20% of patients randomized to the post- op chemoradiotherapy group actually have stage I disease on evaluation of resection specimen These patients will be over-treated if they were treated preoperatively

41. Chemotherapy with preoperative radiotherapy in rectal cancer N Engl J Med 2006;355(11):1114-23 Bosset JF, Collette L, Calais G, et al Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203 J ClinOncol 2006;24(28):4620-5 Gerard JP, Conroy T, Bonnetain F, et al

42. 1011 patients with clinical stage T3 or T4 resectable rectal cancer Randomized to 4 groups: Pre-opPost-op 1RT- 2Chemo-RT- 3RTchemotherapy 4Chemo-RTchemotherapy

43. The cumulative incidences of local recurrences as a first event at 5 years Pre-opPost-opCummulative incidence of local recurrence (%) 1RT-17.1 2Chemo-RT-8.7 3RTchemotherapy9.6 4Chemo-RTchemotherapy7.6 p=0.002 for the comparison between the group receiving preoperative radiotherapy alone and the other three groups

44. 733 patients with T3-4 Nx M0 rectal cancer Randomized to 2 groups –Pre-op radiotherapy group –Pre-op chemoradiotherapy group

45. The 5-year incidence of local recurrence –Pre-op radiotherapy 16.5% –Pre-op chemoradiotherapy8.1% p < 0.05 Overall 5-year survival: –No difference

46. Neoadjuvant therapy with combined chemoradiation is becoming standard of care in locally advanced rectal cancer

48. Surgical resection Resection of the primary tumour With en bloc resection of adjacent involved structures Obtain negative margins Neoadjuvant therapy cannot compensate for irradical resection

49. Conclusions Locally advanced rectal cancer –TNM staging: T3-T4 or N+ –Circumferential resection margin: Tumour < 2mm from the mesorectal fascia Tumour beyond mesorectal fascia Tumour with major lymph node involvement

50. Conclusions MRI with endorectal coil is the best diagnostic tool but not widely available Endorectal ultrasound (ERUS) is widely used with good accuracy

51. Neoadjuvant therapy: –Pre-op radiation therapy combined with chemotherapy –  better local control –No survival benefits shown

52. Conclusions Management of locally advanced rectal cancer is a multidisciplinary cancer management involving diagnostic radiologists, oncologists and surgeons

53. Thank You