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Management of Locally Advanced Management of Locally Advanced Rectal CancerRectal Cancer
Joint Hospital Surgical Grand RoundPamela Youde Nethersole Eastern Hospital
Dr. YH Ling19 May 2007
ColorectalColorectal CancerCancer
Primary modality of treatment:
Surgical Resection
RectalRectal CancerCancer
Middle and lower rectum– Located in the confined
pelvis– Close relationship with
• urogenital tracts• anal sphincters
Goal of treatmentGoal of treatment
Achieve oncological cure– Radical resection
• Negative distal and circumferential margin
Goal of treatmentGoal of treatment
Preserve – Urinary function– Sphincter function– Sexual function
Maintain the quality of life
Radical resection
Pelvic organ functions
Locally advanced rectal cancerLocally 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 controlImproved overall survivalGreater sphincter preservation rate
Treatment of locally advanced rectal
cancer
Multidisciplinary cancer management
Surgeons
Oncologists
Diagnostic radiologists
Locally advanced rectal cancerPre-op stagingNeoadjuvant chemoradiation therapy
Locally advanced rectal cancer
Locally advanced rectal cancerLocally advanced rectal cancer
Tumour and/or regional nodes have invaded the adjacent organs
– T3-4 or N+
– 6-10% of rectal cancer
B1AM0N0T2
D--M1Any NAny TIV
C1/C2/C3CM0N2Any TIIIC
C2/C3CM0N1T3-T4IIIB
C1CM0N1T1-T2IIIA
B3BM0N0T4IIB
B2BM0N0T3IIA
AAM0N0T1I
----M0N0Tis0
MACDukesMNTStage
B1AM0N0T2
D--M1Any NAny TIV
C1/C2/C3CM0N2Any TIIIC
C2/C3CM0N1T3-T4IIIB
C1CM0N1T1-T2IIIA
B3BM0N0T4IIB
B2BM0N0T3IIA
AAM0N0T1I
----M0N0Tis0
MACDukesMNTStage
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 cancerLocally advanced rectal cancer
Tumour growing < 2mm from the mesorectal fascia (fascia proper)
Beyond mesorectal fasciaWith major lymph node involvement
Pre-operative staging
Imaging modalitiesImaging modalities
CT scanMRI
– With or without endorectal coilEndorectal ultrasound
CT scanCT scan
Widely used to stage colorectal cancerNot 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)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)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)Endorectal ultrasound (ERUS)
Limitations:– Stenotic lesion
• Difficult to pass the transducer
– Operator dependent– “Sampling error” for large tumour
MRIMRI
Advantage:– Visualize the
distance between the tumor and the rectal fascia proper
MRIMRI
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 cancerPreoperative staging of rectal cancer
H. Kwok, LP Bissett, GL Hill et alH. Kwok, LP Bissett, GL Hill et alInt J Colorectal Dis (2000) 15:9-20Int J Colorectal Dis (2000) 15:9-20
Systemic review83 studies from 78 papers4897 patients
Bowel wall penetration Nodal status
Acc (%) Sen (%) Spe (%)
Acc (%) Sen (%) Spe (%)
CT 73 78 63 66 52 78
ERUS 87 93 78 74 71 76
MRI 82 86 77 74 65 80
MRI with endorectal coil
84 89 79 82 82 83
MRI with endorectal coilMRI 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 AdvantagesPotential Advantages
Reduction in tumour size – improve resectability– increase sphincter preservation
Decrease risk of local failure– Improve tumour response in the pre-
operative setting
Potential AdvantagesPotential 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 fieldNo delay of therapy in patients with
operative morbidity
Disadvantage:Disadvantage:
Over-treat patient with pre-op overstaged disease
Preoperative staging of rectal cancerPreoperative staging of rectal cancerH. Kwok, LP Bissett, GL Hill et alH. Kwok, LP Bissett, GL Hill et al
Int J Colorectal Dis (2000) 15:9-20Int J Colorectal Dis (2000) 15:9-20
Staging modality
Accuracy (%)
Over-staged (%)
Under-staged (%)
CT 80 13 7
ERUS 84 11 5
MRI 74 13 13
MRI with endorectal coil
81 12 6
Prospective randomized clinical trials that Prospective randomized clinical trials that analyzed neoadjuvant therapy for rectal canceranalyzed neoadjuvant therapy for rectal cancer
Study Year N Main resultsSwedish rectal cancer trial
1997 908 High-dose pre-op radiation therapy reduced local recurrence and improved survival
Dutch colorectal cancer group
2001 1805 Pre-op radiation therapy decreased local recurrence following total mesorectal excision
German rectal cancer study group
2004 823 Pre-op chemoradiation therapy improved local control but did not improve overall survival compared to post-op chemoradiatoin therapy
Rectal cancerT3 or T4 or N +
Long course radiation+
Infusional 5-FUTME
TMERadiation therapy
+Infusional 5-FU
n = 415 n = 384
6 weeks
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
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):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
1011 patients with clinical stage T3 or T4 resectable rectal cancer
Randomized to 4 groups:
Pre-op Post-op
1 RT -
2 Chemo-RT -
3 RT chemotherapy
4 Chemo-RT chemotherapy
The cumulative incidences The cumulative incidences of local recurrences as a of local recurrences as a first event at 5 yearsfirst event at 5 years
Pre-op Post-op Cummulative incidence of local
recurrence (%)
1 RT - 17.1
2 Chemo-RT - 8.7
3 RT chemotherapy 9.6
4 Chemo-RT chemotherapy 7.6
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 chemoradiotherapy 8.1%
• 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 resectionSurgical resection
Resection of the primary tumourWith en bloc resection of adjacent
involved structuresObtain negative margins
Neoadjuvant therapy cannot compensate for irradical resection
ConclusionsConclusions
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
ConclusionsConclusions
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
ConclusionsConclusions
Management of locally advanced rectal cancer is a multidisciplinary cancer management involving diagnostic radiologists, oncologists and surgeons
ThankThank YouYou