management of locally advanced rectal cancer
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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 - PowerPoint PPT PresentationTRANSCRIPT
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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
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ColorectalColorectal CancerCancer
Primary modality of treatment:
Surgical Resection
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RectalRectal CancerCancer Middle and lower
rectum– Located in the confined
pelvis– Close relationship with
• urogenital tracts• anal sphincters
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Goal of treatmentGoal of treatmentAchieve oncological cure
– Radical resection • Negative distal and circumferential
margin
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Goal of treatmentGoal of treatmentPreserve
– Urinary function– Sphincter function– Sexual function
Maintain the quality of life
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Radical resection
Pelvic organ functions
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Locally advanced rectal cancerLocally advanced rectal cancer
Tumour and/or regional nodes have invaded the adjacent organs– Bladder, ureters– seminal vesicles, prostate– vagina– sacrum
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Pre-op imaging and staging
Surgery
RadiotherapyChemotherapy
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Better local disease controlImproved overall survivalGreater sphincter preservation rate
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Treatment of locally advanced rectal
cancer
Multidisciplinary cancer management
SurgeonsOncologists
Diagnostic radiologists
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Locally advanced rectal cancerPre-op stagingNeoadjuvant chemoradiation therapy
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Locally advanced rectal cancer
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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
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B1AM0N0T2
D--M1Any NAny TIVC1/C2/C3CM0N2Any TIIIC
C2/C3CM0N1T3-T4IIIBC1CM0N1T1-T2IIIA
B3BM0N0T4IIBB2BM0N0T3IIA
AAM0N0T1I----M0N0Tis0
MACDukesMNTStage
B1AM0N0T2
D--M1Any NAny TIVC1/C2/C3CM0N2Any TIIIC
C2/C3CM0N1T3-T4IIIBC1CM0N1T1-T2IIIA
B3BM0N0T4IIBB2BM0N0T3IIA
AAM0N0T1I----M0N0Tis0
MACDukesMNTStage
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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
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Locally advanced rectal cancerLocally advanced rectal cancer
Tumour growing < 2mm from the mesorectal fascia (fascia proper)
Beyond mesorectal fasciaWith major lymph node involvement
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Pre-operative staging
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Imaging modalitiesImaging modalitiesCT scanMRI
– With or without endorectal coilEndorectal ultrasound
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CT scanCT scanWidely 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
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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.
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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
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Endorectal ultrasound (ERUS)Endorectal ultrasound (ERUS)
Limitations:– Stenotic lesion
• Difficult to pass the transducer– Operator dependent– “Sampling error” for large tumour
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MRIMRIAdvantage:
– Visualize the distance between the tumor and the rectal fascia proper
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MRIMRILimitation:
– 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
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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
Systemic review83 studies from 78 papers4897 patients
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Bowel wall penetration Nodal statusAcc (%) Sen (%) Spe
(%)Acc (%) Sen (%) Spe (%)
CT 73 78 63 66 52 78ERUS 87 93 78 74 71 76MRI 82 86 77 74 65 80MRI with endorectal coil
84 89 79 82 82 83
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MRI with endorectal coilMRI with endorectal coil
Most useful technique for preoperative staging of rectal cancer
Limited availabilityLimits its routine use
Limited use in stenotic lesions
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Neoadjuvant chemoradiation therapy
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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
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Potential AdvantagesPotential AdvantagesDecrease 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
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Disadvantage:Disadvantage:Over-treat patient with pre-op
overstaged disease
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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
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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
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Rectal cancerT3 or T4 or N +
Long course radiation+
Infusional 5-FUTME
TMERadiation therapy
+Infusional 5-FU
n = 415 n = 384
6 weeks
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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
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Improved sphincter preservation rates in pre-op chemoradiation therapy group
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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
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Chemotherapy with preoperative radiotherapy in rectal cancer
N Engl J Med 2006;355(11):1114-23Bosset 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):4620-5Gerard JP, Conroy T, Bonnetain F, et al
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1011 patients with clinical stage T3 or T4 resectable rectal cancer
Randomized to 4 groups:
Pre-op Post-op1 RT -2 Chemo-RT -3 RT chemotherapy4 Chemo-RT chemotherapy
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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 - 17.12 Chemo-RT - 8.73 RT chemotherapy 9.64 Chemo-RT chemotherapy 7.6
p=0.002 for the comparison between the group receiving preoperative radiotherapy alone and the other three groups
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733 patients with T3-4 Nx M0 rectal cancer
Randomized to 2 groups– Pre-op radiotherapy group– Pre-op chemoradiotherapy group
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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
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Neoadjuvant therapy with combined chemoradiation is becoming
standard of care in locally advanced rectal cancer
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Surgical resectionSurgical resection
Resection of the primary tumourWith en bloc resection of adjacent
involved structuresObtain negative margins
Neoadjuvant therapy cannot compensate for irradical resection
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ConclusionsConclusionsLocally 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
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ConclusionsConclusionsMRI with endorectal coil is the best
diagnostic tool but not widely available
Endorectal ultrasound (ERUS) is widely used with good accuracy
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Neoadjuvant therapy:– Pre-op radiation therapy combined with
chemotherapy better local control– No survival benefits shown
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ConclusionsConclusionsManagement of locally advanced
rectal cancer is a multidisciplinary cancer management involving diagnostic radiologists, oncologists and surgeons
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ThankThank YouYou