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Vascular Invasion (VI) is a better prognostic
indicator in pT4 colorectal cancer than
subtyping into pT4a v. pT4b: analysis of 276
cases and validation in an independent
patient cohort
Sreekumar R, Bhome R, Turck R, Bruce A
Bullock M, Cheung T, Yano H, Mirnezami AH
Content
Background
Hypothesis
Methodology
Results
Conclusion
Background
AJCC TNM 7th
ed.
pT4a = Penetrates to the surface
of visceral peritoneum
pT4b = Directly invades or is
adherent to neighbouring organs
AJCC Cancer Staging Manual, 7tth
ed. 2009
pT4a pT4b
SEER Data 2010
1. Gunderson LL, Jessup JM, Sargent DJ et al Revised TN Categorization for Colon Cancer Based
on National Survival Outcomes Data. J Clin Oncol 2010 28:264-71
2. Compton C, Fenoglio-Preiser CM, Pettigrew N, et al. American Joint Committee on Cancer
Prognostic Factors Consensus Conference: Colorectal Working Group. Cancer. 2000;88:1739–
1757.
• pT4a superior 5-yr outcomes by nodal
status
• Contrary to previous AJCC data
• Long term outcomes unpredictable
• Need for additional prognostic markers
Vascular Invasion
Smith NJ, Shihab O, Arnaout A et al. MRI for detection of
extramural vascular invasion in rectal cancer. AJR 2008;
191:1517-22
“Presence of
malignant cells
within endothelial
cell-lined vessels
beyond muscularis
propria”
Objectives
1. Evaluate a prospective database of pT4 CRC for clinico-
pathological variables and survival outcomes
2. Compare survival outcomes for pT4a v. pT4b and pT4 VI+ v. VI-
3. Assess external validity in an independent patient cohort
Hypothesis/ Objectives
Vascular Invasion is a better prognostic marker of survival in
pT4 CRC than subtyping into T4a and T4b
Methods
Prospective database of all T4 CRC resections with curative intent (University Hospitals Southampton, 2004-2011)
Relevant clinico-pathological and follow up data evaluated
(i) Vascular Invasion status (ii) pT4a/b subtype
correlated with long-term outcomes
Kaplan-Meier survival curves generated
Multivariate Cox regression analysis undertaken
Validate findings in an independent patient cohort (National Centre for Global Health and Medicine Japan)
Outcome data for T4a v. T4b (UK)
n = 270
T4a = 214
T4b = 56
p=0.508
T4a
T4b
Cancer specific survival (Months)
Cu
mu
lati
ve
su
rviv
al
T4b
T4a
Outcome data for Vascular Invasion status (UK)
n = 270
VI positive = 106
VI negative = 164
p<0.001
VI -ve
VI +ve
Cancer specific survival (Months)
Cu
mu
lati
ve
su
rviv
al
VI +ve
VI -ve
Outcome data for T4a v. T4b (Japan)
n = 207
T4a = 144
T4b = 63
p=0.783
T4a
T4b
Cancer specific survival (Months)
Cu
mu
lati
ve
su
rviv
al
T4a
T4b
Outcome data for Vascular Invasion status (Japan)
n = 207
VI positive = 135
VI negative = 72
p<0.001
VI +ve
Cancer specific survival (Months)
Cu
mu
lati
ve
su
rviv
al
VI -ve
Multivariate Analysis
Characteristic Hazard Ratio CI p-value
Vascular Invasion (UK) 2.433 1.630-3.633 0.001
Vascular Invasion (Japan) 2.553 1.379-4.725 0.003
T4a v. T4b (UK) 1.517 0.950-2.421 0.081
T4a v. T4b (Japan) 0.950 0.563-1.604 0.847
Cancer specific survival
Conclusion
• Vascular invasion is a better
prognostic indicator in pT4 CRC than
subtyping into pT4a and pT4b
• No significant survival difference
between T4a and T4b
• Vascular invasion not yet considered
in AJCC/ TNM
Clinico-pathological correlation (UK)
Factor CATEGORIES
Vascular invasion +VE Vascular invasion -VE p – value
Age (yrs) <50
>50
5
103
6
159
0.683
Sex M
F
60
83
48
82
0.39
SITE ASC.
DESC.
RECTUM
59
44
5
80
68
17
0.213
Resection
margin
R0
R1
R2
89
18
1
145
19
0
0.220
STAGE II
III
IV
20
53
30
73
64
24
0.001
NM status N0M0
N+M0
N+M+
20
53
30
73
64
24
0.001
Differentiation POOR
MOD-POOR
MODERATE
MOD-WELL
WELL
26
11
28
41
2
21
7
45
85
7
0.016
T4a v. T4b T4A
T4B
15
93
42
121
0.019
Clinico-pathological correlation
(Japan) Factor CATEGORIES
Vascular invasion -VE Vascular invasion +VE p – value
Age <60
>60
13
57
57
110
0.65
Sex M
F
39
35
69
63
0.95
SITE RIGHT
LEFT
RECTUM
7
6
7
46
53
33
0.64
Resection margin R0
R1
R2
47
5
22
69
8
55
0.23
STAGE DUKES B
DUKES C
DUKES D
24
26
24
23
43
66
0.01
N STAGE N0
N1
N2
N3
31
28
10
5
42
44
30
16
0.17
T4a v. T4b T4A
T4B
52
22
90
42
0.76
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