Hepatic Colorectal Metastasis: How Curable Metastatic Colorectal Cancer Much Progress Have We Made? Definition •cure \ ’ ky ù r\ n [ME, fr. OF, fr. ML &L; ML cura , fr. L, care ](14c) …a complete or permanent solution or remedy… vb… to restore to health or normality; to free from something harmful… William R. Jarnagin, MD, FACS Curable Metastatic Colorectal Cancer Definition •Treatment of metastatic colorectal cancer: • How is cure achieved? ‘While several series have reported 5-year survival rates � Complete resection of all disease of 25%, comparison has been made only with has been � Imperfect: recurrence in 80% made only with retrospective data, an invalid control. � Chemotherapy may improve results of resections Thus, it is not known if resection of these lesions is appropriate... •Surgery for metastatic colorectal cancer (liver): The morbidity and mortality of resection come close to • What are the real long-term results? offsetting any advantage of resection…’ � Is cure a realistic objective? � Are we curing patients or deferring recurrence? Arch Surg 1989;124:1021 1
Hepatic Resection Results of contemporary series Study n 5-yr Surv (%) “Before you can prove Hughes, 1986 607* 33 Scheele, 1991 219 39 that an operation is valuable, Rosen, 1992 280 25 Scheele, 1995 469 39 you must be able to do it Nordlinger, 1995 1568* 28 Jamison, 1997 280 27 without killing people” Fong, 1999 1001 37 Choti, 2002 226 40 de Jong, 2009 1669* 47 Leslie H. Blumgart House, 2010 1600 43 * - Multicenter study Hepatic Resection Hepatic Resection: Patient Selection Long-term survival: divergent outcomes 1.0 Clinical risk score (CRS): risk stratification 1985 – 94 612 Patients with follow-up � 10 yrs .8 • Node (+) colorectal primary Median Survival = 44mos % Surviving ● • Disease-free interval < 1 year .6 <2 yrs • More than 1 hepatic tumor .4 • Largest hepatic tumor > 5 cm 2-5 ● yrs • CEA > 200 ng/mL .2 5-10 yrs >10 yrs n=101 1 point for each criterion 0 Clinical risk score = sum 0 5 10 15 Years Fong et al Ann Surg 1999;230:309 Tomlinson et al JCO 2007;25:4575 2
Hepatic Resection: Patient Selection Hepatic Resection: Patient Selection 10-year survival stratified by CRS What precludes long-term survival? 1 .0 Survival < 2 Years > 10 years 0 .8 Proportion Surviving Node (+) Primary 63% 50% > 1 Hepatic Tumor 59% 39% 0 .6 Disease-Free Interval < 1Year 51% 36% CRS Low CRS 0 0 .4 1 n = 359 Largest Tumor Size > 5cm 53% 35% 2 Resection extent ( � Lobe) 63% 68% 0 .2 3 High CRS � 4 Hepatic Tumors 4 23% 5% n = 161 5 0 .0 Margin (+) Hepatic Resection 20% 0% 0 60 1 2 0 1 8 0 2 40 Months Tomlinson et al JCO 2007;25:4575 Tomlinson et al JCO 2007;25:4575 Metastatic Colorectal Cancer Resectability •Definition of resectable is a moving target • 1970 ’ s – Noone • 1980 ’ s – � 3 unilobar tumors • Gene expression profile • 19 genes identify low/high risk groups • Molecular risk score (MRS) • 1990 ’ s – Multiple bilobar tumors • MRS combined with CRS • 2000 and beyond… • Effective stratification of survival after resection � Major impact of contemporary systemic agents � Redefined traditional definition of resectability PLoS 2012;8(12) 3
Systemic Chemotherapy Metastatic Colorectal Cancer More active agents for patients with incurable disease This patient underwent a complete resection of all disease February 2009 November •Dramatic improvement in efficacy 2013 •Progressive increase in survival Metastatic Colorectal Cancer Systemic Chemotherapy Improvement in outcome over time Impact on patients with resectable disease Recurrence-Free Survival • Retrospective review of 279 Taiwanese patients • Era I: pre-2003 • What are the benefits in patients with potentially resectable tumors? • Era II: post-2003 • Is the same improvement in outcome being realized? Era 2 • Median FU: 27 months Era 1 • Recurrence: 75% (median 9 months) • Perception that chemotherapy is greatly improving survival Era I Era II Overall Survival • Is this valid? Variable (n=128) (n=151) p • Resulting in cure or delayed time to recurrence? Age 59 y 63 y 0.009 Era 2 Multiple tumors 24% 44% <0.0001 Contemporary chemotx 31% 88% <0.0001 Resection of recurrence 10% 30% 0.003 Era 1 Chan et al. World J Surg Oncol 2011;9:174 4
Metastatic Colorectal Cancer Two-Stage Hepatic Resection Two-stage hepatic resection for advanced liver disease Hepatic resection in the face of extrahepatic disease PVE Before • 75 patients • R0 resection of liver metastases plus extrahepatic disease • Extrahepatic sites: peritoneum, lymph nodes, lung, ovary After • Extensive use of chemotherapy • 29% NED, median FU = 5 years Elias et al Ann Surg Onc 2004;11(3):274 Kianmanesh et al. JACS 2003 197:164 Metastatic Colorectal Cancer ‘ Neo-adjuvant ’ chemotherapy •Chemotherapy prior to hepatic resection • With 1 o in situ if asymptomatic • 107 Patients with liver and peritoneal dz • 1995 – 2006 • Hepatic resection •Rationale • Cytoreduction • IP Chemotherapy • No delay in starting treatment • Extensive systemic chemotherapy • ‘ In vivo ’ assessment of response • Better patient selection/improved results of resection • Overall Survival • 5-year = 35% � ? Improved survival with response • 10-year = 15% � ? No benefit of resection with no response Ann Surg 2013;257:1065 Allen P et al. J Gastrointest Surg 2003;7:109 5
Metastatic Colorectal Cancer ‘ Neo-adjuvant ’ chemotherapy Before • 196 patients with initially unresectable disease • FOLFOXIRI – 11 cycles, median = 5.5 months • Response rate = 70% After • Complete resection = 20% (37 patients) � 5-year overall survival = 42% � Disease recurrence in 31 of 37 (84%) •Potential to improve resectability Masi et al. Ann Surg 2009;249:420 • Analysis of patients treated with preoperative chemotherapy • Analysis of published studies (n = 503) • Resectable disease • Patients with initially unresectable disease • Irinotecan- or oxaliplatin-based • Treated with systemic chemotherapy • 5-year survival correlated with treatment response • Strong correlation between treatment response • Complete (n = 25) - 75% and overall resection rate • Major (n = 97) - 56% • Minor (n = 149) - 33% 6
Hepatic Resection: Safety Study n Mortality (%) Hughes, 1986 607* NS Scheele, 1991 219 6 Rosen, 1992 280 4 Optimism meets reality Scheele, 1995 469 4 Nordlinger, 1995 1568* 2 Jamison, 1997 280 4 Fong, 1999 1001 3 Choti, 2002 226 1 de Jong, 2009 1669* NS House, 2010 1600 2† * - Multicenter study. † - 90 day mortality ‘ Neo-Adjuvant ’ Chemotherapy Hepatic Resection: Safety Operative mortality (n = 1010) The other side of the sword: Liver injury 6 5 4 % 3 2 1 0 1992-97 1998-99 2000-01 Steatosis/steatohepatitis Sinusoidal congestion (n=550) (n=245) (n=215) Jarnagin et al. Ann Surg 2002;236:397 7
‘ Neo-Adjuvant ’ Chemotherapy Steatosis/steatohepatitis and operative morbidity • Major hepatectomy in 89 patients • Resectable disease •406 patients treated with pre-operative chemotherapy • Preoperative chemotherapy • 5-FU, FOLFOX or FOLFIRI • Chemotherapy •Steatohepatitis (34 patients) • Increased operative morbidity • Associated with preoperative irinotecan � 38% vs. 14%, p =0.03 � 20% vs. 4% for no chemotherapy (p < 0.001) • Correlation between morbidity and • Higher 90-day mortality # cycles � 15% vs. 2% for no steatohepatitis Vauthey et al. JCO 2006;24:2065 Karoui et al. Ann Surg 2006;243:1 ‘ Neo-Adjuvant ’ Chemotherapy Morbidity after Hepatic Resection Impact on long-term outcome Steatosis/steatohepatitis and operative morbidity 75 MSKCC: Matched control study (n = 485) ■ Morbidity (p<0.01) Overall Survival • Prospective trial ■ Infections (p<0.01) • Major resections (>3 segs) 50 No Complications (n=50) ■ Mortality (p=NS) Complications (n=50) • Equivalent disease extent % • CRS � 3 in 43% and 45% % 25 • Postoperative morbidity N=160 N=223 N=102 • Independent predictor 0 Normal Mild Marked Steatosis Steatosis Time (months) •Mortality: 3.1% � 3.6% � 5.9% Kooby et al. JOGS 2003;7:1034 Correa et al 2013 Ann Surg Oncol 8
Recommend
More recommend
