Transcript 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 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 cancer
pathologic evaluation
circumferential resection margin
% 100 50 CRM (+) CRM (-) 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 T Stage EUS Sensitivity Specificity 93% MRI/coil 89% 78% 79% N Stage EUS 71% MRI/coil 82% 76% 83% Kwok 2000
MRI staging
circumferential margin
Prediction of Involved CRM
Beets-Tan 2004
% 50
local recurrence
surgeon as risk factor
surgeon minimum 25 rectal cancer operations per surgeon Holm 1997
rectal cancer
know your surgeon!
circumferential resection margin
% 100 50 CRM (+) CRM (-) 0 local recurrence survival Adam 1995
% 0 25
rectal cancer surgery
impact of technique
p < 0.0001* p < 0.002* Stockholm I Stockholm II TME project 15 16 9 15 14 6 local recurrence cancer deaths * Stockholm I and II vs TME project 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
30 local recurrence (%) 15 rectal cancer
radiation + chemo
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
CT/RT surgery only BM / 24 hr nighttime BMs occasional incontinence frequent incontinence pad unable to defer BM 15' (%) 7 46 39 7 41 78 (%) 2 14 17 0 10 19 Kollmorgen 1994
short course rt
long-term morbidity
dvt femoral neck / pelvic fractures sbo fistulas RT (+) (%) 7.5
5.3
RT (-) (%) 3.6
2.4
13.3
4.8
8.5
1.9
p 0.01
0.03
0.02
0.01
Holm 1996
radiation therapy
controversies
• patient selection –
who needs adjuvant therapy?
• timing –
pre- or postoperative?
• technique –
short or conventional course?
% 0 27 surgery +/- rt
local recurrence
SRCT Dutch TME Trial 8 11 2 surgery/ RT surgery
100 % 50 82 surgery +/- rt
2-year survival
p=0.84
82 0 surgery surgery/ RT Dutch TME Trial
pre
• biology • downstaging – resectability – sphincter salvage – margins • sb complications • functional results rectal cancer
radiation timing
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 10% 2% 4% 4% 27% Post-Op 12% 3% 6% 12%* 40%* Sauer, NEJM 2005
German rectal cancer study Downstaging Sphincter Preservation Local Recurrence Survival * p<0.05
Pre-Op 8% 39% 6% 76% Post-Op 19%* 13%* 74% Sauer, NEJM 2005
short vs. long course United States: 45-54 Gy OR 6 weeks Europe: 25 Gy 1 week OR
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 (%) 50 47 18 0 0 T1 T1: local excision T2: local excision; no chemoradiation T2 6 local excision radical surgery 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 T 1 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% 36-67% 53-88% avg 22% avg 60% avg 65%
risk stratification
within T stage
differentiation well moderate poor 9% positive nodes T1 T2 4% 12% 20% 13% 48%
submucosal invasion
Japanese classification
Kikuchi nodal metastasis
Japanese classification
Sm 1 0% Sm 2 10% Sm 3 39% Nivatvongs 2.9% 7.5% 23%
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*) 1 11 17
*follow-up 12 months 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 function optimal 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