1. Treatment strategies for colon cancer at TNM stage IV Gunnar Arbman Department of Surgery Norrköping, Sweden Bergen June 2011

3. Definitions Stage IV colon cancer: Any T, any N, M1 (a + b) UICC: metastases diagnosed within 2 months from surgery are classified as synchronous R 0 resection: All tumour (primary + metastases) resected with microscopically clear margins

4. Should the primary tumour in stage IV be resected in patients who cannot be cured?

5. Treatment strategies Traditional strategy: Resect primary tumour and then start oncologic therapy Alternative strategy: Oncologic therapy directly, leave the primary tumour in place if possible

6. To treat the most serious aspect of the disease first, without having to wait for recovery after bowel surgery or complications, is appealing however to leave primary tumours with proven metastatic capacity may have consequences

7. The scientific support for both strategies is weak. Studies are retrospective and of different designs.

8. Palliative studies Years R/Ch Survival mo Difference Matheme et al73-9281/707,5/2,5-5 Liu et al86-9157/1111/3-8 Scoggins et al85-9766/2314,5/16,62 Cook et al88-00 17656/909711-16/2-6-9-10 Temple et al91-99 6469/254210/3-7 Terbutt et al90-00280/8214/8,2-6 Ahmed et al92-00594/2199,7/3,3-6 Konyalin et al91-0262/4712,3/4,5-8 Cummins et al89-0336/3811,5/4,5-7 Ruo et al96-99127/10316/9-7 Law et al96-99150/307/4-3 Stelzner et al95-01128/5811,4/4,6-7 Michel et al96-9931/2321/14-7 Benoist et al97-0232/2723/22-1 Galizia et al95-0542/2315,2/12,3-3 Kaufman et al98-03115/2122/15-7 Bajwa et al99-0532/3814/6-8 Koopman et al03-05368/15116,8/12,2-4 Cellini et al02-0822/932/375

9. Metaanalyses Scheer et al 20087 studies ”primary resection provides minimal palliative benefit, risk for major morbidity/mortality and delays chemotherapy” Eisenberg et al 2008 12 studies ”non-curative resection may prolong survival” Stillwell et al 2010 8 studies ”primary resection improves survival and avoids the need for emergency surgery”

10. Stent study Frago (2010): 52 patients with generalized left sided colon cancer and obstruction +/- perforation 12 patients resected because of perforation (6) or stent complications (6) 40 patients with primary tumour left i place with stents or stomas (5, due to stent complications) All had the same type of chemotherapy Median survival: Resected24 months Not resected4 months

11. Conclusion There is not enough evidence to state if the primary tumour should be resected or not, but it may be that removing the primary tumour prolongs life in the palliative situation. Randomized studies are needed to clarify this.

12. PGC-trial Swedish (Scandinavian) multicenter prospective randomized trial comparing the two strategies. Primary endpoint is median survival. www.clinicaltrials.gov Studies in GB and Australia/NZ as well