Local recurrence after rectal cancer resection is strongly related to the plane of surgical (PoS) dissection and is further reduced by pre-operative short course radiotherapy Preliminary results of the MRC CR07/NCIC C016 randomised trial Phil Quirke on behalf of the trial investigators and the UK NCRI colorectal cancer study group
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Phil Quirke on behalf of the trial investigators and the UK NCRI colorectal cancer study group
Local recurrence after rectal cancer resection is strongly related to the plane of surgical (PoS) dissection and is further reduced by pre-operative short course radiotherapy Preliminary results of the MRC CR07/NCIC C016 randomised trial. Phil Quirke on behalf of the trial investigators - PowerPoint PPT Presentation
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Local recurrence after rectal cancer resection is strongly related to the plane of surgical (PoS) dissection and is further
reduced by pre-operative short course radiotherapy
Preliminary results of theMRC CR07/NCIC C016 randomised trial
Phil Quirke on behalf of the trial investigators
and the UK NCRI colorectal cancer study group
Phil Quirke
Randomise
Clinically operable adenocarcinoma of the rectum <15cm from anal verge; no metastases
Adjuvant chemotherapy given as per local policy
PRE POST
Pre-operative RT25Gy / 5F
Surgery
Surgery
Pathology (Pos)
CRM-ve CRM+ve
Post-op CRT45Gy / 25F
+ concurrent5FU
No RT
Trial Design
Pathology (PoS)
CRM-ve CRM+ve
Key questions
In terms of local recurrence, how important is:
• The surgical circumferential margin (CRM)?
• The plane of surgical dissection?
• Short course pre-operative radiotherapy?
High quality pathology
Prospective
Protocol defined specimen dissection and written proforma reporting
Individual pathology training days and central approval
Standardised pathology • circumferential margin • TNM version 5
CRM +ve ≤1mm
0
10
20
30
40
50
60
70
80
90
100
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5Time (years)
LR
ra
te %
LR by CRM status (all patients)
CRM +ve
CRM -ve
Events/N 3yr LR 5yr LR
CRM -ve 60/1107 6% 9%CRM +ve 18/139 18% 25%
HR 4.21 (95%CI 2.00,6.50) p=0.0001
CRM by treatment
0
10
20
30
40
50
60
70
80
90
100
0 12 24 36 48 60
CRM –ven=1107
CRM +ven=139
POST
0
10
20
30
40
50
60
70
80
90
100
0 12 24 36 48 60
POSTPRE PRE
Months Months
HR 2.91 (1.74-4.88) HR 1.56 (0.6-4.04)
Prospective assessment of the plane of surgical (PoS) dissection
Randomise
Clinically operable adenocarcinoma of the rectum <15cm from anal verge; no metastases
Adjuvant chemotherapy given as per local policy
PRE POST
Pre-operative RT25Gy / 5F
Surgery
Surgery
Pathology (PoS)
CRM-ve CRM+ve
Post-op CRT45Gy / 25F
+ concurrent5FU
No RT
Trial Design
Pathology (PoS)
CRM-ve CRM+ve
Abbreviated definitions of surgical plane (predefined and prospectively graded)
Mesorectal plane: intact mesorectum with only minor irregularities of a smooth mesorectal surface. No defect deeper than 5mm. No coning, smooth CRM on slicing
Intramesorectal plane: Moderate bulk to meso-rectum but irregularity of the mesorectal surface. Moderate distal coning. Muscularis propria not visible with the exception of levator insertion. Moderate irregularity of CRM
Muscularis propria plane: Little bulk to mesorectum with defects down onto muscularis propria and/or very irregular CRM
Plane of surgery n=1119 (83%)
Mesorectal Intra-mesorectal
Muscularis propria
n=596
53%
n=382
34%
n=141
13%
CRM+ve rate by year
0
5
10
15
20
25
1998 1999 2000 2001 2002 2003 2004 2005
Year
Perc
en
tag
e
Plane of surgery by year
Mesorectal plane Intramesorectal plane Muscularis propria plane
0
25
50
75
100
1998 1999 2000 2001 2002 2003 2004 2005
Year
Perc
en
tag
e
Associations with plane
PlaneMesorectal Intra- Muscularis
mesorectal propria
CRM +ve rate 9%12% 19%
Stage I 28%24% 28% Stage II 26%32% 30% Stage III 46%45% 42%
0
10
20
30
40
50
60
70
80
90
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5Time (years)
LR
rate
(%
)LR by plane of surgery
Events N 3yr LR 5yr LRMesorectal plane 22 596 4% 8%Intramesorectal plane 22 382 8% 9%Muscularis propria plane 16 141 15% 21%