Extramural Vascular Invasion (EMVI) is a better prognostic ...€¦ · Sreekumar R, Bhome R, Turck R, Bruce A Bullock M, Cheung T, Yano H, Mirnezami AH . Content Background Hypothesis

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