Synchronous Hepatic Colorectal Metastases: Old Dilemma, New Problems

1. Synchronous Hepatic Colorectal Metastases:Old Dilemma, New Problems Shaun McKenzie, MD Assistant Professor of Surgery University of Kentucky

2. Objectives Review the literature driving the controversies behind available approaches Emphasize the complexity involved in the multidisciplinary management of these patients Propose a baseline algorithm to scaffold an ever evolving treatment strategy

3. Definition: the presence of hepatic metastases identified at the time of diagnosis of the primary tumor or within 6 months of diagnosis Approximately 2400 US patients present with Synchronous CRC Hepatic Metastases annually These patients compromise 15-25% of new cases of CRC per year They compromise 25-50% of most large hepatic resection series for CRC They are believed to represent a patient population with aggressive biology and poor prognosis Synchronous Hepatic CRC

4. Is Synchronous Disease Worse • Many retrospective studies and clinical risk scores have incorporated disease free interval as a poor prognostic factor • Several recent series have questioned whether synchronous resectable disease is worse than metachronous resectable disease • Bockhorn et al compared 63 pts with synchronous disease to 63 pts with metachronous disease: no difference in DFS or OS • Minagawa et all show no difference in survival comparing 3,5,10 year survival of 187 vs. 184 pts respectively • Capisotti et al noted 5 year survival of 30% for patients with resected synchronous disease Reddy et al. Ann Surg Oncol 2009; 16:2395-2410

5. Survival Comparison after Hepatectomy

6. Synchronous Versus Metachronous Disease in All Patients

7. Reddy et al. Ann Surg Oncol 2009; 16:2395-2410

8. Unresectable Hepatic Metastases Muratore et al. Ann Surg Oncol 2007; 14:766-70

9. Leave the Primary Poultsides et al

10. Adam et al. JCO 2009; 27:1829-1835

11. Resectable Hepatic Metastases Aloia, Fahy. Clin Colorectal CA 2008; 7:197-201

12. EORTC Intergroup Trial 40983 RCT 182 patients per arm 6 cycles FOLFOX 4 pre and post resection vs. hepatectomy alone Need for Chemotherapy Nordlinger et al. Lancet 2008; 371:1007-17

13. Timing of Chemotherapy: Do we know? P<0.001

14. Gallagher et al.

15. Simultaneous Vs Staged Resections Reddy et al. Ann Surg Oncol 2007; 14:3481-3491

16. Simultaneous versus Staged: Louisville Experience Martin et al

17. Liver First Mentha et al. Br J Surg 2006; 93:872-78

18. Case by Case Decision Making Broquet et al. JACS 2010, 210:934-941.

19. High Risk Disease

20. The Prognostic Primary

21. Preoperative chemotherapy induces a liver injury that may increase perioperative morbidity and postoperative hepatic dysfunction Portal Vein Embolization allows hypertrophy of the Future Liver Remnant (FLR) in patients requiring extended resections or after prolonged courses of prehepatectomy chemotherapy Requires a 4-6 week waiting period prior to resection Concerns exist regarding its effectiveness during chemotherapy and its oncologic effect PVE

23. Pamecha et al.

25. Two Stage

26. The Evolving Algorithm Synchronous Hepatic CRC Unresectable hepatic disease Resectable disease Minor Hepatectomy Needed Major hepatectomy Needed chemotherapy Simultaneous resection Followed by chemotherapy Inadequate response Resectable Colon Primary Rectal Primary Bilobar disease Colon Resection Hepatectomy Chemotherapy Continue chemotherapy Or enter a trial R/S Neoadjuvant CRT + rectal resection P N1 N2 Primary +FLR dz First, +/-PVE, hepatectomy Hepatectomy then chemo Chemo then hepatectomy Chemo

27. Questions