Download Slide 1

Multimodality Therapy
of Rectal Cancer
Robert D. Madoff, MD
University of Minnesota
rectal cancer
clinical issues
• colostomy or anastomosis?
• local or radical surgery?
• functional outcomes?
• neoadjuvant therapy?
rectal cancer therapy
morbidity
mortality
optimal
function
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 cancer
pathologic evaluation
circumferential resection margin
100
%
CRM (+)
CRM (-)
50
0
local recurrence
survival
Adam 1995
rectal cancer
stage dictates
therapy
rectal cancer
know your
enemy!
uT1
uT3
uN1
Preop Staging
• Review of 83 studies including 4897 patients
Sensitivity Specificity
T
EUS
93%
Stage
MRI/coil 89%
78%
N
EUS
71%
Stage
MRI/coil 82%
76%
79%
83%
Kwok 2000
MRI staging
circumferential margin
Prediction of Involved
CRM
Beets-Tan 2004
local recurrence
surgeon as risk factor
50
%
surgeon
minimum 25 rectal cancer operations per surgeon
Holm 1997
rectal cancer
know your
surgeon!
circumferential resection margin
100
%
CRM (+)
CRM (-)
50
0
local recurrence
survival
Adam 1995
rectal cancer surgery
impact of technique
25
p < 0.0001*
p < 0.002*
Stockholm I
Stockholm II
TME project
%
15
15
14
16
9
6
0
local recurrence
* Stockholm I and II vs TME project
cancer deaths
Lehander Martling 2000
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 cancer
radiation + chemo
30
local
recurrence
(%)
15
25
14
0
RT
RT + CT
Krook 1991
rectal cancer
radiation + chemo, vs. TME alone
30
local
recurrence
(%)
15
25
14
6
0
RT
RT + CT
TME
Krook 1991
Heald 1998
radiation therapy
friend
or
friendly fire?
radiation therapy
disadvantages
• cost
• convenience
• complications
• covering stomas
• quality of life
postop chemoradiation
functional results
BM / 24 hr
CT/RT
surgery only
(%)
(%)
7
2
nighttime BMs
46
14
occasional incontinence
39
17
7
0
pad
41
10
unable to defer BM 15'
78
19
frequent incontinence
Kollmorgen 1994
short course rt
long-term morbidity
dvt
RT (+)
(%)
7.5
RT (-)
(%)
3.6
p
0.01
femoral neck /
pelvic fractures
sbo
5.3
2.4
0.03
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
SRCT
%
Dutch TME Trial
11
8
2
0
surgery
surgery/ RT
surgery +/- rt
2-year survival
p=0.84
100
82
82
%
50
0
surgery
surgery/ RT
Dutch TME Trial
rectal cancer
radiation timing
pre
• biology
• downstaging
– resectability
– sphincter salvage
– margins
• sb complications
• functional results
post
• staging accuracy
– avoids
overtreatment
• anastomotic leak
risk
– covering stomas
German rectal cancer study
823 patients - Stage II-III
50.4 Gy RT +
Chemo
OR (TME)
OR (TME)
50.4 Gy RT +
Chemo
Sauer 2003
German rectal cancer study
Leak
Bleed
Delayed healing
Stricture
Acute toxicity
Pre-Op
Post-Op
10%
2%
4%
4%
27%
12%
3%
6%
12%*
40%*
Sauer, NEJM 2005
German rectal cancer study
Pre-Op
Post-Op
Downstaging
8%
Sphincter
Preservation
39%
19%*
Local
Recurrence
6%
13%*
Survival
76%
74%
* p<0.05
Sauer, NEJM 2005
short vs. long course
United States:
45-54 Gy
OR
6 weeks
Europe:
25 Gy
OR
1 week
short course radiation
pro
• convenience
• cost
• effectiveness
con
• unsafe if given
improperly
• ? higher rate of late
toxic effects
• cannot give
simultaneously
with chemotherapy
short course vs.
conventional radiation
no data!
radiation therapy
current 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 CANCER
AS BREAST CANCER:
PARADIGM FOUND?
pensa globalmente…
…agisci localmente
RECTAL CANCER
LOCAL 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 therapy
results
25
local
recurrence
(%)
14
3
T1
T1: local excision
T2: local excision plus chemoradiation
T2
CALGB 8984
local excision vs.
radical surgery
100
local
recurrence
(%)
local excision
radical surgery
47
50
18
6
0
0
T1
T1: local excision
T2: local excision; no chemoradiation
T2
Garcia-Aguilar 2000
“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 recurrence
local excision T1 rectal cancer
25
%
18
15
17
UMN 2000
MSKCC 2005
CCF 2005
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 involvement
resected colorectal cancer
T stage
T1
T2
T3
T4
positive nodes
0-18%
avg 8%
12-38% avg 22%
36-67% avg 60%
53-88% avg 65%
risk stratification
within T stage
positive nodes
differentiation
T1
T2
well
4%
12%
moderate
9%
20%
poor
13%
48%
submucosal invasion
Japanese classification
nodal metastasis
Japanese classification
Kikuchi
Sm1
Sm2
Sm3
0%
10%
39%
7.5%
23%
Nivatvongs 2.9%
local excision is
first a complete
excisional
biopsy
local excision
pathologic exclusion criteria
•
•
•
•
T stage > T1 Sm3
positive or equivocal margins
poor differentiation
lymphovascular invasion
SALVAGE SURGERY
STATUS
29 patients
unresectable hepatic mets
additional recurrence
free of disease
(positive margin, NED 3*)
*follow-up 12 months
1
11
17
Friel 2002
SALVAGE SURGERY
AFTER 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 excision
preoperative chemoradiation?
• downstages tumor
–? curative in some patients
• may reduce risk of tumor
implantation at excision site
rectal cancer therapy
morbidity
mortality
optimal
function
cure rate
rectal cancer
conclusions
• 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