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

Colorectal Cancer Primary modality of treatment: Surgical Resection

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

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

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

Radical resection Pelvic organ functions

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

Pre-op imaging and staging Surgery RadiotherapyChemotherapy

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

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

Locally advanced rectal cancer Pre-op staging Neoadjuvant chemoradiation therapy

Locally advanced rectal cancer

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

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

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

Pre-operative staging

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

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

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.

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

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

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

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

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

Bowel wall penetrationNodal status Acc (%)Sen (%)Spe (%)Acc (%)Sen (%)Spe (%) CT ERUS MRI MRI with endorectal coil

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

Neoadjuvant chemoradiation therapy

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

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

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

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

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

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

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

Improved sphincter preservation rates in pre-op chemoradiation therapy group

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

Chemotherapy with preoperative radiotherapy in rectal cancer N Engl J Med 2006;355(11): 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): Gerard JP, Conroy T, Bonnetain F, et al

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

The cumulative incidences of local recurrences as a first event at 5 years Pre-opPost-opCummulative incidence of local recurrence (%) 1RT Chemo-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

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

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

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

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

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

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

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

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

Thank You