Should pulmonary metastases from colorectal cancer

be resected?

Tom Treasure MD MS FRCS FRCPClinical Operational Research UnitUCL (Department of Mathematics)

London

http://www.ctsnet.org/home/ttreasure

My starting point:

If I get colorectal cancer• I would be grateful for

your skill to control the primary cancer

• I’d hope for a cureBUT• If you fail to cure me ...

I will want to know the evidence base for any further treatment offered

Antony Gormley’s“Field”

Reported series with 40% 5 year survival• not a random sample• are from an unknown denominator• with great variation amongst individuals

A solitary nodule – what is it?• Colorectal metastasis• Primary lung cancer• Something else

1. Clinical context2. Smoking history3. Radiological review (Lindell Radiology 2007)4. Tissue diagnosis5. If intraoperative diagnosis

work up with NSCLC in mind

Evaluation

• Patient– Age– Sex– Symptoms – FEV1

• Cancer– Date of primary CRC resection (interval)– Stage of primary at CRC resection– Present control/status (including PET)– Number of metastases– Carcinoma embryonic antigen (CEA)

When not to offer metastactomy?

• Short interval – how short?• Multiple metastases – how many?• Raised CEA – mixed messages!

Annals Thoracic Surgery 2009;87:1685

N=3781998 to 2007DukeMSK-CC

When not to offer metastactomy?

• Short interval – NOT < 12 months• Multiple metastases – NOT > 3• Raised CEA – the CEA paradox

Annals Thoracic Surgery 2009;87:1685

N=3781998 to 2007DukeMSK-CC

Survival by CEA

0

10

20

30

40

50

60

70

80

90

100

1960 1970 1980 1990 2000

Mid-point of reported series

Prop

ortio

n of

pat

ient

s su

rviv

ing

to 5

yea

r

CEA Norm <50

CEA Norm 50-100

CEA Norm >100

CEA High <50

CEA High 50-100

CEA High >100

JAMA 1994;272:31JTO 2010;5:S179

Where is the evidence?

• 51 surgical follow up studies• 3504 patients• 1960s to 2000s

Survival

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10 11

years

Perc

enta

ge o

f sur

vivi

ng p

atie

nts

Series <50

Series 50-100

Series >100

Median survival <50

Survival averages 40%... in selected patients

Evidence based on *• 60% solitary metastasis• 36 months interval

* JRSM 2010;103:60** JTO 2008;3:1257

Practice 146 ESTS members ** • Multiple no obstacle 85%• <12 months alright 93%• Synchronous alright 73%

Increasing interval between the primary resection and the metastasectomy

ManyMets

OneMet

J Thorac Oncol 2010; 5(6 Suppl 2):S200-S202

A thought experiment ...

Modelling outcomes on Thames Cancer Registry data

Country

Year Patients 5 YS Reported(95% confidence

intervals)

5 YS byModel

USA 1992 144

Japan 1996 159

Arch Surg 1992; 127:1403J Thorac Cardiovasc Surg 1996; 112:867

“Better out than in” Utley et al. Proceedings of the 33rd International Conference on Operational Research Applied to Health Services

0

0.1

0.2

0.3

0.4

0.5

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0.7

0.8

0.9

1

0 12 24 36 48 600

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

0 12 24 36 48 60 72 84 96 108 120

Survival

Time following resection of primary

Modelling withThames Cancer Registry data

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

0 12 24 36 48 60 72 84 96 108 120

Dukes A

Dukes B

Dukes C

unknown

Dukes D

Thanks to South Thames Cancer Registry, UK

5 yr survival 75% - 10%

Months

Proportion of patients still alive

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

0 12 24 36 48 60

Proportion of patients still aliveJ Thorac Cardiovasc Surg. 1996 Oct;112(4):867-74

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

0 12 24 36 48 60

Proportion of patients still alive

Modelling outcomes on Thames Cancer Registry data

Country

Year Patients 5 YS Reported(95% confidence

intervals)

5 YS byModel

USA 1992 144 55%

Japan 1996 159 50%

Arch Surg 1992; 127:1403J Thorac Cardiovasc Surg 1996; 112:867

“Better out than in” Utley et al. Proceedings of the 33rd International Conference on Operational Research Applied to Health Services

Modelling outcomes on Thames Cancer Registry data

Country

Year Patients 5 YS Reported(95% confidence

intervals)

5 YS byModel

USA 1992 144 40% (32%-48%) 55%

Japan 1996 159 41% (33%-48%) 50%

Arch Surg 1992; 127:1403J Thorac Cardiovasc Surg 1996; 112:867

“Better out than in” Utley et al. Proceedings of the 33rd International Conference on Operational Research Applied to Health Services

Two closing thoughts

• Belief is more powerful than evidence• But trials can bring a surprise

33

Blalock 1944• Ranks 13th of 293 unique cited papers• Cited by 14/51 index papers

(High five 31,30,27,22,22)

34

New England J Medicine1944; 231:261-267

35Annals of Thoracic Surgery 1980;30:378

36

N = 100, 385, 121, 208

2007 MD Anderson 2008 New York collected 2009 Boston 2007 MSK-CC

And finally: thank you for you interest!

If I get colorectal cancer• I would be grateful for

your skill to control the primary cancer

• I’d hope for a cureBUT• If you fail, please do

NOT use up the rest of my days in unavailing therapies.