Multimodality Therapy of Rectal Cancer
Robert D. Madoff, MD
University of Minnesota
rectal cancerclinical issues
• colostomy or anastomosis?
• local or radical surgery?
• functional outcomes?
• neoadjuvant therapy?
rectal cancer therapy
morbidity
mortality
function
optimal
cure rate
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
rectal cancerpathologic evaluation
circumferential resection margin
Adam 1995
0
50
100
local recurrence survival
CRM (+)
CRM (-)
%
rectal cancer
stage dictates therapy
rectal cancer
know your enemy!
uT1
uT3uN1
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%
MRI stagingcircumferential margin
Prediction of Involved CRM
Beets-Tan 2004
local recurrencesurgeon as risk factor
surgeon
50
%
minimum 25 rectal cancer operations per surgeon Holm 1997
rectal cancer
know your surgeon!
circumferential resection margin
Adam 1995
0
50
100
local recurrence survival
CRM (+)CRM (-)
%
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
Combined postoperative chemotherapy and radiation therapy improves local control and survival in Stage II and III patients and is recommended.
NIH Consensus Statement, 1990
rectal cancerradiation + chemo
25
14
0
15
30
RT RT + CT
local
recurrence
(%)
Krook 1991
rectal cancerradiation + chemo, vs. TME alone
25
6
14
0
15
30
RT RT + CT TME
local
recurrence
(%)
Krook 1991
Heald 1998
radiation therapy
friendor
friendly fire?
radiation therapydisadvantages
• cost
• convenience
• complications
• covering stomas
• quality of life
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
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
radiation therapy controversies
• patient selection–who needs adjuvant therapy?
• timing–pre- or postoperative?
• technique–short or conventional course?
surgery +/- rt local recurrence
27
11
8
2
0
surgery surgery/ RT
SRCT
Dutch TME Trial%
surgery +/- rt 2-year survival
82 82
0
50
100
surgery surgery/ RT
%
Dutch TME Trial
p=0.84
rectal cancerradiation timing
• biology• downstaging
– resectability– sphincter salvage– margins
• sb complications• functional results
• staging accuracy– avoids
overtreatment
• anastomotic leak risk– covering stomas
pre post
German rectal cancer study
823 patients - Stage II-III
50.4 Gy RT + Chemo
OR (TME)
50.4 Gy RT + ChemoOR (TME)
Sauer 2003
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%*
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
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
short course radiation
• convenience
• cost
• effectiveness
• unsafe if given improperly
• ? higher rate of late toxic effects
• cannot give simultaneously with chemotherapy
pro con
short course vs. conventional radiation
no data!
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
RECTAL CANCERAS BREAST CANCER:PARADIGM FOUND?
pensa globalmente…
…agisci localmente
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
non usare un cannone per sperare ad una pulce…
…ma prima assicurati che sia proprio ad una pulce che
stai sparando!
local therapyresults
3
14
T1 T2
25
local recurrence
(%)
CALGB 8984T1: local excisionT2: local excision plus chemoradiation
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
“Dr. Mellgren and colleagues deserve to be congratulated for their honesty…”
Steele 2000
“…remarkably bad outcome… significantly worse than any previously reported…”
“the University of Minnesota experience stands alone…”
Steele 2000
local recurrencelocal excision T1 rectal cancer
1815
17
UMN 2000
MSKCC 2005
CCF 2005
25
%
CALGB 8984
Steele 1999
TEM results
superior to transanal excision!
TME VS. TMN
local excision:
TOTAL MESORECTAL NEGLECT!
select tumors with
a low likelihood of
regional metastases
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%
risk stratification within T stage
positive nodes
differentiation T1 T2
well 4% 12%
moderate 9% 20%
poor 13% 48%
submucosal invasionJapanese classification
Sm1 Sm2 Sm3
Kikuchi 0% 10% 39%
Nivatvongs2.9% 7.5% 23%
nodal metastasis Japanese classification
local excision is first a complete
excisional biopsy
local excisionpathologic exclusion criteria
• T stage > T1 Sm3
• positive or equivocal margins
• poor differentiation
• lymphovascular invasion
SALVAGE SURGERYSTATUS
29 patients
unresectable hepatic mets 1additional recurrence 11free of disease 17
(positive margin, NED 3*)
Friel 2002*follow-up 12 months
SALVAGE SURGERYAFTER LOCAL EXCISION
don’t count on it!
LOCAL EXCISION
primum non nocere!
It is the wise surgeon who understands that the patient takes all the risk.
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
local excisionpreoperative chemoradiation?
• downstages tumor–? curative in some patients
• may reduce risk of tumor implantation at excision site
rectal cancer therapy
morbidity
mortality
function
optimal
cure rate
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
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