1. Should pulmonary metastases from colorectal cancer be resected? Tom Treasure MD MS FRCS FRCP Clinical Operational Research Unit UCL (Department of Mathematics) London http://www.ctsnet.org/home/ttreasure http://www.ctsnet.org/home/ttreasure

2. 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 cure BUT If you fail to cure me... I will want to know the evidence base for any further treatment offered

6. 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

8. A solitary nodule – what is it? Colorectal metastasis Primary lung cancer Something else 1.Clinical context 2.Smoking history 3.Radiological review (Lindell Radiology 2007) 4.Tissue diagnosis 5.If intraoperative diagnosis work up with NSCLC in mind

10. 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)

13. When not to offer metastactomy? Short interval – how short? Multiple metastases – how many? Raised CEA – mixed messages! Annals Thoracic Surgery 2009;87:1685 N=378 1998 to 2007 Duke MSK-CC

14. 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=378 1998 to 2007 Duke MSK-CC

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

18. Where is the evidence? 51 surgical follow up studies 3504 patients 1960s to 2000s

20. 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%

21. Increasing interval between the primary resection and the metastasectomy Many Mets One Met J Thorac Oncol 2010; 5(6 Suppl 2):S200-S202 A thought experiment...

22. Modelling outcomes on Thames Cancer Registry data Countr y YearPatients5 YS Reported (95% confidence intervals) 5 YS by Model USA1992144 Japan1996159 Arch Surg 1992; 127:1403 J 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

23. Survival Time following resection of primary Modelling with Thames Cancer Registry data

24. 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

25. J Thorac Cardiovasc Surg. 1996 Oct;112(4):867-74

26. Proportion of patients still alive

27. Modelling outcomes on Thames Cancer Registry data Countr y YearPatients5 YS Reported (95% confidence intervals) 5 YS by Model USA199214455% Japan199615950% Arch Surg 1992; 127:1403 J 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

28. Modelling outcomes on Thames Cancer Registry data Countr y YearPatients5 YS Reported (95% confidence intervals) 5 YS by Model USA199214440% (32%-48%)55% Japan199615941% (33%-48%)50% Arch Surg 1992; 127:1403 J 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

32. Two closing thoughts Belief is more powerful than evidence But trials can bring a surprise

33. 33 Blalock 1944 Ranks 13 th of 293 unique cited papers Cited by 14/51 index papers (High five 31,30,27,22,22)

34. 34 New England J Medicine 1944; 231:261-267

35. 35 Annals of Thoracic Surgery 1980;30:378

36. 36

38. N = 100, 385, 121, 208 2007 MD Anderson 2008 New York collected 2009 Boston 2007 MSK-CC

39. 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 cure BUT If you fail, please do NOT use up the rest of my days in unavailing therapies.