Multimodality Therapy of Rectal Cancer
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Transcript of Multimodality Therapy of Rectal Cancer
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Multimodality Therapy of Rectal Cancer
Robert D. Madoff, MD
University of Minnesota
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rectal cancerclinical issues
• colostomy or anastomosis?
• local or radical surgery?
• functional outcomes?
• neoadjuvant therapy?
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rectal cancer therapy
morbidity
mortality
function
optimal
cure rate
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total mesorectal excision
• the rectum and its mesentery are a single fascia-enveloped unit, anatomically separate from surrounding pelvic structures
• surgical violation of this anatomic package leads to a positive circumferential margin, a known predictor of local recurrence
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rectal cancerpathologic evaluation
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circumferential resection margin
Adam 1995
0
50
100
local recurrence survival
CRM (+)
CRM (-)
%
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rectal cancer
stage dictates therapy
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rectal cancer
know your enemy!
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uT1
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uT3uN1
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Preop Staging• Review of 83 studies including 4897 patients
Kwok 2000
Sensitivity Specificity
T Stage
EUS 93% 78%
MRI/coil 89% 79%
N Stage
EUS 71% 76%
MRI/coil 82% 83%
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MRI stagingcircumferential margin
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Prediction of Involved CRM
Beets-Tan 2004
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local recurrencesurgeon as risk factor
surgeon
50
%
minimum 25 rectal cancer operations per surgeon Holm 1997
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rectal cancer
know your surgeon!
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circumferential resection margin
Adam 1995
0
50
100
local recurrence survival
CRM (+)CRM (-)
%
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rectal cancer surgeryimpact of technique
15 1514 16
6
9
0
25
local recurrence cancer deaths
Stockholm IStockholm IITME project
Lehander Martling 2000
%
p < 0.0001* p < 0.002*
* Stockholm I and II vs TME project
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Combined postoperative chemotherapy and radiation therapy improves local control and survival in Stage II and III patients and is recommended.
NIH Consensus Statement, 1990
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rectal cancerradiation + chemo
25
14
0
15
30
RT RT + CT
local
recurrence
(%)
Krook 1991
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rectal cancerradiation + chemo, vs. TME alone
25
6
14
0
15
30
RT RT + CT TME
local
recurrence
(%)
Krook 1991
Heald 1998
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radiation therapy
friendor
friendly fire?
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radiation therapydisadvantages
• cost
• convenience
• complications
• covering stomas
• quality of life
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postop chemoradiationfunctional results
CT/RT surgery only
(%) (%)
BM / 24 hr 7 2
nighttime BMs 46 14
occasional incontinence 39 17
frequent incontinence 7 0
pad 41 10
unable to defer BM 15' 78 19
Kollmorgen 1994
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short course rtlong-term morbidity
RT (+)
(%)
RT (-)
(%)
p
dvt 7.5 3.6 0.01
femoral neck / pelvic fractures
5.3 2.4 0.03
sbo 13.3 8.5 0.02
fistulas 4.8 1.9 0.01
Holm 1996
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radiation therapy controversies
• patient selection–who needs adjuvant therapy?
• timing–pre- or postoperative?
• technique–short or conventional course?
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surgery +/- rt local recurrence
27
11
8
2
0
surgery surgery/ RT
SRCT
Dutch TME Trial%
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surgery +/- rt 2-year survival
82 82
0
50
100
surgery surgery/ RT
%
Dutch TME Trial
p=0.84
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rectal cancerradiation timing
• biology• downstaging
– resectability– sphincter salvage– margins
• sb complications• functional results
• staging accuracy– avoids
overtreatment
• anastomotic leak risk– covering stomas
pre post
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German rectal cancer study
823 patients - Stage II-III
50.4 Gy RT + Chemo
OR (TME)
50.4 Gy RT + ChemoOR (TME)
Sauer 2003
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German rectal cancer study
Sauer, NEJM 2005
Pre-Op Post-Op
Leak 10% 12%Bleed 2% 3%Delayed healing 4% 6%Stricture 4% 12%*Acute toxicity 27% 40%*
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Downstaging 8%
Sphincter Preservation 39% 19%*
LocalRecurrence 6% 13%*
Survival 76% 74%
German rectal cancer study
Sauer, NEJM 2005
Pre-Op Post-Op
* p<0.05
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short vs. long course
United States:United States:
Europe:Europe:
45-54 Gy45-54 Gy
6 weeks6 weeks
OROR
OROR
1 week1 week
25 Gy25 Gy
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short course radiation
• convenience
• cost
• effectiveness
• unsafe if given improperly
• ? higher rate of late toxic effects
• cannot give simultaneously with chemotherapy
pro con
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short course vs. conventional radiation
no data!
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radiation therapycurrent status (USA)
• optimally stage patient (ERUS)
• conventional (long course) RT plus chemotherapy for stage II (T3), stage III (N1) or stage IV cancers
• postoperative chemoradiation for positive circumferential margin
• consider postoperative chemoradiation for understaged T3 or N1 lesions
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RECTAL CANCERAS BREAST CANCER:PARADIGM FOUND?
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pensa globalmente…
…agisci localmente
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RECTAL CANCERLOCAL EXCISION
pro–low morbidity/mortality–avoids sexual/urinary/bowel dysfunction–avoids colostomy
con–nodal status not pathologically assessed–involved nodes not excised–? equivalent oncologic results to radical excision
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non usare un cannone per sperare ad una pulce…
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…ma prima assicurati che sia proprio ad una pulce che
stai sparando!
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local therapyresults
3
14
T1 T2
25
local recurrence
(%)
CALGB 8984T1: local excisionT2: local excision plus chemoradiation
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local excision vs.radical surgery
T1: local excisionT2: local excision; no chemoradiation
local recurrence
(%)
Garcia-Aguilar 2000
18
47
06
0
50
100
T1 T2
local excision
radical surgery
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“Dr. Mellgren and colleagues deserve to be congratulated for their honesty…”
Steele 2000
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“…remarkably bad outcome… significantly worse than any previously reported…”
“the University of Minnesota experience stands alone…”
Steele 2000
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local recurrencelocal excision T1 rectal cancer
1815
17
UMN 2000
MSKCC 2005
CCF 2005
25
%
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CALGB 8984
Steele 1999
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TEM results
superior to transanal excision!
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TME VS. TMN
local excision:
TOTAL MESORECTAL NEGLECT!
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select tumors with
a low likelihood of
regional metastases
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risk of nodal involvementresected colorectal cancer
T stage positive nodes
T1 0-18% avg 8%
T2 12-38% avg 22%
T3 36-67% avg 60%
T4 53-88% avg 65%
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risk stratification within T stage
positive nodes
differentiation T1 T2
well 4% 12%
moderate 9% 20%
poor 13% 48%
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submucosal invasionJapanese classification
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Sm1 Sm2 Sm3
Kikuchi 0% 10% 39%
Nivatvongs2.9% 7.5% 23%
nodal metastasis Japanese classification
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local excision is first a complete
excisional biopsy
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local excisionpathologic exclusion criteria
• T stage > T1 Sm3
• positive or equivocal margins
• poor differentiation
• lymphovascular invasion
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SALVAGE SURGERYSTATUS
29 patients
unresectable hepatic mets 1additional recurrence 11free of disease 17
(positive margin, NED 3*)
Friel 2002*follow-up 12 months
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SALVAGE SURGERYAFTER LOCAL EXCISION
don’t count on it!
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LOCAL EXCISION
primum non nocere!
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It is the wise surgeon who understands that the patient takes all the risk.
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local excision rules of engagement
• selection, selection, selection!– ERUS stage first, but reassess pathologic specimen– no “winking” at adverse histology or inadequate
margins
• adjuvant chemoradiation for pT2 tumors• mandate close follow up• remember that recurrent tumors are almost
always more advanced than they start, and radical salvage surgery cures only 50% of patients
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local excisionpreoperative chemoradiation?
• downstages tumor–? curative in some patients
• may reduce risk of tumor implantation at excision site
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rectal cancer therapy
morbidity
mortality
function
optimal
cure rate
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rectal cancerconclusions
• numerous treatment permutations• appropriate treatment depends upon tumor
stage, which should be determined before surgery
• surgery is technically driven; optimal results require training and experience
• role of local therapy remains controversial• oncologic cure is the primary goal, but
functional results are an important outcome