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Multimodality therapy
for rectal cancer
Carlo Aschele
Oncologia Medica B
Istituto Nazionale per la Ricerca sul Cancro - Genova
Highlights in the management of gastrointestinal cancer
Roma - May 21-22, 2010
LOCAL FAILURE AND SITE
OF RECTAL CANCER
tumor
site
odds
ratio
upper
third
0.43
middle/
lower
third
1.0
95%
c.i.
0.24-0.77
p=0.004
Hermanek, 1995
EFFECT OF RT ON LOCAL FAILURE
AND SITE OF RECTAL CANCER
Dutch TME trial
cm from
anal verge
2-y LR, %
RT+TME
TME
p
0-5
5.8
10
0.05
5-10
1.0
10.1
<0.001
10-15
1.3
3.8
0.17
NEJM, 2001
CHI?
• SOTTO LA RIFLESSIONE PERITONEALE
• ENTRO 12 CM DALLA RIMA ANALE
INTERVENTO- RETTOSCOPIA (STR RIGIDO)-RMN
età-sesso-altezza-peso-condizioni
ginecologiche ed ostetriche
(nord vs sud europa)
anteriore vs posteriore
Locally advanced rectal cancer
• perirectal fat penetration
• adjacent organ invasion
• lymphnode infiltration
• mesorectal fascia (CRM) involvement
TRUS - CT scan - MRI
Tx neoadiuvante del carcinoma del retto
Patient selection
- tumor location
- tumor stage
Standard treatment
Chemotherapy
– role (concomitant and adjuvant)
– simplification / potentiation
Surgery / pathology
Standard vs selective approach
Tx neoadiuvante del carcinoma del retto
Patient selection
- tumor location
- tumor stage
Standard treatment
Chemotherapy
– role (concomitant and adjuvant)
– simplification / potentiation
Surgery / pathology
Standard vs selective approach
IMPACT OF POST-OP CMT
T3 and/or N+
local failure, %
5-y survival, %
GITSG 7175
Mayo/NCCTG
79-47-51
86-47-51
11
INT 0114
14
64
NSABP R-02
9
62-65
Compared
to surgery alone:
~ 50
~ 15-25
14
9-11
54
53
60-70 (4-y)
LOCALLY ADVANCED RECTAL CANCER.
IMPACT OF ADJUVANT CMT ON SURVIVAL
(NCCTG 794751, 864751; NSABP R01, R02; INT 0114. N=3791)
Gunderson, L. L. et al. J Clin Oncol; 22:1785-1796 2004
Copyright © American Society of Clinical Oncology
Post-op chemoradiation
Compliance
46-76 %
Acute toxicity
(grade III-IV)
Long-term toxicity
26-53 %
46-56 %
NCCTG 79-4751 / 86-4751; GITSG 7175 ; NSABP R02; CAO/ARO/AIO 94
CAO/ARO/AIO-94
50.4 Gy
CI FU
TME
FU x 4 cy
TME
50.4 Gy
CI FU
FU x 4 cy
R
CAO/ARO/AIO-94
TME SURGERY
5-y outcome
Post-op
(n=394)
Pre-op
(n=405)
p
Survival %
LF %
74
13
76
6
0.80
0.006
acute toxicity
chronic toxicity
40
24
27
14
0.001
0.01
NEJM 2004
PRE-OP CHEMORADIATION:
IMPACT ON SPHINCTER SAVING
CAO/ARO/AIO-94
declared to
require APR
sphincter-saving
surgery
Post
78
19 % (15/78)
Pre
116
39 % (45/116)
p
0.004
NEJM 2004
Standard treatment of locally
advanced rectal cancer
T3-4 and/or N+
RT
CT
45-50.4
Gy
T
M
E
Pre-op RT vs. surgery alone:
Risk of local recurrence in phase III trials
Role of chemotherapy
PRE-OP RT +/- CONCOMITANT CT
pCR, %
RT
RT + CT
EORTC
5
14
FFCD
3
10
Bosset, NEJM 2006; Gerard, JCO 2006
Role of chemotherapy
PRE-OP RT +/- CONCOMITANT CT
5-y LR, %
RT
RT + CT
EORTC
17
8
FFCD
16
8
Bosset, NEJM 2006; Gerard, JCO 2006
NSABP R-04
RT + Capecitabine +/- oxaliplatin
R
S
RT + CI 5-FU +/- oxaliplatin
N=1460
STAR-01
R
n=747
ypT0(N0)
RT 50.4 Gy
FU 225 mg/m2/day PVI
16%
6-8
wks
RT 50.4 Gy
FU 225 mg/m2/day PVI
OXA 60 mg/m2 weekly x 6
T
M
E
p=0.94
16%
ACCORD
R
n=598
RT 45 Gy
CAPE 1600 mg/m2/day
14%
6-8
wks
RT 50 Gy
CAPE 1600 mg/m2/day
OXA 50 mg/m2 weekly x 5
T
M
E
p=0.11
19%
ASCO ‘09
Standard treatment of locally
advanced rectal cancer
T3-4 and/or N+
RT
CT
45-50.4
Gy
T
M
E
Blunt dissection
LR
20–40%
TME
5–10%
Fascial plane
In mesorectum
In/on muscularis
Dataset for colorectal cancer (2° edition), RCOP, 2007
SURGERY QUALITY:
EFFECT OF THE PLANE OF SURGERY ON
LOCAL RECURRENCE
Circumferential resection margin
LOCAL RECURRENCE AND CRM
Nagtegaal, I. D. et al. J Clin Oncol; 26:303-312 2008
Copyright © American Society of Clinical Oncology
Standard treatment of locally
advanced rectal cancer
T3-4 and/or N+
RT
CT
45-50.4
Gy
T
M
E
FU-based adjuvant chemotherapy in rectal
cancer patients. QUASAR study (n=948).
survival
Effect of FU-based adjuvant chemotherapy in
colon and rectal cancer patients. QUASAR study
Recurrence
n = 3239
Effect of adjuvant FU-based chemotherapy
in rectal cancer patients included in the
QUASAR study
Recurrence at any time
n = 948
Lancet 2008; 371: 1503
CAO/ARO/AIO-94
50.4 Gy
CI FU
TME
FU x 4 cy
TME
50.4 Gy
CI FU
FU x 4 cy
R
LOCALLY ADVANCED RECTAL CANCER.
IMPACT OF ADJUVANT CMT ON SURVIVAL
(NCCTG 794751, 864751; NSABP R01, R02; INT
0114. N=3791)
+ Adj Chemo
Surg +/- RT
Gunderson, L. L. et al. J Clin Oncol; 22:1785-1796 2004
ECOG 5204
* RT + bolus or CI FU ± LV, or Cape
or NSABPR 04
Effect of adjuvant chemotherapy in pts with good
and poor response to pre-op treatment
DFS
JCO, 2007
Tx neoadiuvante del carcinoma del retto
Patient selection
- tumor location
- tumor stage
Standard treatment
Chemotherapy
– role (concomitant and adjuvant)
– simplification / potentiation
Surgery / pathology
Standard vs selective approach
Standard treatment of locally
advanced rectal cancer
RT
CT
45-50.4
Gy
T
M
E
Optimal for every LARC patient?
n=188 (TRUS 130 / MRI 58)
22 % node + after pre-op CRT
n
3-y LR
5-y LR
routine pre
674
4%
5%
selective post
676
11%
12 %
HR=0.39 (95% CI 0.27-0.58); p<0.0001
•pT3<5mm, N any
T2 and early T3
tumours <5mm
have 85-90% 5
year cancer
specific survival.
MERKEL et al 2001
STANDARD vs SELECTIVE
APPROACH
• almeno 7-8 cm dalla rima anale
• infiltrazione grasso < 5 mm (MERCURY)
• non evidenza di linfonodi patologici
• margine radiale atteso di almeno 2 mm
• chirurgo dedicato
• TME con mesoretto integro e CRM • pT3a-bN0 (almeno 12 linfonodi negativi)
• G1-G2
patients’ preference
Rectal cancer:
adjuvant / neoadjuvant treatment
STOMA THERAPIST
NURSE
RADIOTHERAPIST
SURGEON
CURE
QOL
RADIOLOGIST
PATHOLOGIST
MEDICAL ONCOLOGIST