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Penn Cancer Center. Surgical and Ablative Strategies for Treatment of Metastatic Colorectal Cancer. Kim M. Olthoff, MD Associate Professor of Surgery Liver Transplantation and Hepatobiliary Surgery University of Pennsylvania Philadelphia, Pennsylvania, USA. Colorectal Cancer Demographics.
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Penn Cancer Center Surgical and Ablative Strategies for Treatment of Metastatic Colorectal Cancer Kim M. Olthoff, MD Associate Professor of Surgery Liver Transplantation and Hepatobiliary Surgery University of Pennsylvania Philadelphia, Pennsylvania, USA
Colorectal Cancer Demographics • Fourth most common cancer in the United States • Second leading cause of cancer death • An estimated 146,940 cases will be diagnosed, with 56,700 deaths resulting from CRC • Lifetime risk of developing CRC is 6% • 90% of CRC cases occur in patients over 50 years old • Poor long-term survival in Stage IV disease (<5%) • Only 40% of patients in the United States detected through screening Cancer Facts & Figures 2004. American Cancer Society. Treatment Algorithms: Colorectal Cancer 5th Edition. Datamonitor 2003.
CRC Stage at Diagnosis 13.7% Stage I 21.2% Stage IV 27.9% Stage II 37.2% Stage III Treatment Algorithms: Colorectal Cancer 5th Edition. Datamonitor 2003.
CRC: Treatment by Stage • Stage I • Surgery • Stage II • Surgery, adjuvant chemotherapy (controversial) • Stage III • Surgery and adjuvant chemotherapy • Stage IV • Primary chemotherapy; resection of metastatic disease when possible Treatment Algorithms: Colorectal Cancer 5th Edition. Datamonitor 2003.
Colorectal Metastases to the Liver • The most common site of metastases from CRC • 50%-75% of patients with advanced CRCwill develop liver metastases • 15%-25% of patients have liver metastases at presentation • 20%-35% of patients have metastatic disease confined to the liver Kemeny and Fata. J Hepatobiliary Pancreat Surg. 1999;6:39.Seifert et al. J R CollSurg Edinb. 1998;43:141. Borner. Ann Oncol. 1999;10:623.
Colorectal Cancer Metastatic to the LiverOutline • Surgical indications • Surgical approaches • Strategies to increase resectability • Adjuvant therapy • Ablative therapy
Strategies for Metastatic Colorectal Cancer Surgical Decision Making Metastatic Disease Assessment of Resectability Tumor conference discussion Resectable Unresectable Surgery Neoadjuvant ? Chemotherapy Ablative therapy Adjuvant
< Lobe > Lobe All n=370 n=631 n=1,001 Periop mortality (%) 0.5 4 2.8 Median survival (mos) 46 39 42 5 year survival (%) 40 33 37 Strategies for Metastatic Colorectal Cancer Prognosis 1,001 Patients at MSKCC 1985-1998 Fong et al, Ann Surg 1999; 230:309
Hepatectomy for Colorectal MetastasesSurgical Decision Making Multivariate Analysis of Survival (N=1,001) Factor % p Hazard > 1 Tumor 51 0.0004 1.5 CEA > 200 ng/ml 9 0.01 1.5 Size > 5 cm 45 0.01 1.4 Node + primary 60 0.02 1.3 Dz-free interval < 1 yr 49 0.03 1.3 Positive micro margin 11 0.004 1.7 Extrahepatic disease 9 0.003 1.7 Postop Preop Fong et al, Ann Surg 1999; 230:309
Hepatectomy for Colorectal Metastases Surgical Decision Making Preop Clinical Risk Score Predicts Survival Survival Score Median 5 year 0 74 months 60% 1 51 44 2 47 40 3 33 20 4 20 25 5 22 14 The problem with scoring: no one preoperative factor can be used to exclude Fong et al, Ann Surg 1999; 230:309
Number 5 year of tumors N survival (%) 4 49 33 5 38 22 6 - 8 23 19 9-20 45 14 155 23 Hepatectomy for Colorectal MetastasesSurgical Decision Making Liver Metastases >4 Conclusion: Take an Aggressive Surgical And Adjuvant Therapy Approach! Ann Surg Onc 2000; 7:643
Hepatectomy for Colorectal MetastasesStaged vs Simultaneous Operations No difference in major complications or survival Martin et al JACS 2003; 197:233
Hepatectomy for Colorectal MetastasesSurgical Decision Making: Laparoscopy 50 40 Unresectable Disease Present 30 % Identified at 20 Laparoscopy 10 0 Score < 3 Score > 3 N=57 N=45 Cancer 2001; 91:1191
Surgical Approaches: Intra-operative Ultrasound Operative U/S probes (open) T probe Finger-grip probe Microvascular flow probe Open abdomen curvilinear probe Laparoscopic U/S probes Rigid laparoscopic probe 4-way flexible laparoscopic probe End-fire probe
Intra-op U/S of IVC and 3 hepatic veins LHV MHV RHV IVC
Techniques for Dividing Liver Parenchyma/Achieving Hemostasis Monopolar cautery (bovie) Blunt fracture/clips Argon Beam Coagulator Ultrasonic dissector (CUSA) Harmonic scalpel Ligasure Endovascular stapler Fibrin glue Erbe Hydrojet TissueLink Floating Ball/ DS3.0/3.5
Surgical Approaches Laparoscopic resection of liver tumor
Hepatectomy for Colorectal MetastasesAdvantages of laparoscopic liver surgery • Band-aid sized incisions • Less pain • Shorter LOS • No blood transfusions • No oncological disadvantages
Port placement: lap. resection R. lobe 5 mm 5 mm 12 mm Old, open incision 11 mm 5 mm
X 5 mm - retractor X 12 mm - Stapler 12 mm - Scope X X Scissors TissueLink Argon Harmonic Suction irrig. 5 mm (working) Port Placement for Lap. resection of R. lobe tumor lesion
Laparoscopic partial R hepatic lobectomy 44 yo F, 5 cm lesion Ideal lesion
X 12 mm - Stapler X 5 mm - working X 12 mm - Scope Hand port Port sites for Lap. hand-assisted resection R. lobe tumor lesion
12 mm 5 mm 5 mm 12 mm Hand port No post-op pain, d/c’d home on POD #2
Lap. hand-assisted L lateral segmentectomy 72 yo WM, met to liver tumor Cut edge of liver tumor Resected LLS
Strategies to increase resectabilityof liver metastases • Portal vein embolization • 2 stage hepatectomy • In situ and ex vivo resection • Downstaging chemotherapy • 5-FU with leucovorin or folinic acid • Irinotecan hydrochloride (CPT-11) • Oxaliplatin • Local ablation techniques • Cryotherapy, RFA
Survival Outcomes in CRC Patients With Liver Metastasis: Role of Neoadjuvant Irinotecan- or Oxaliplatin-Based Therapy 100 80 58/77 patients had complete resection 60 % Survival 77 patients resected (complete and partial) after chemotherapy 40 20 74 nonoperative patients 0 0 1 2 3 4 5 6 7 8 9 Years CRC Patients With Resected Liver Metastasis after downstaging (n=77) CRC Patients With Liver Metastasis(n=151) 5-y survival (%) 28 50 Median OS (mo) 24 48 Topham and Adams. Semin Oncol. 2002:29:3.
Hepatic Resection of Colorectal MetastasesStrategies to increase resectability: Ablation • Goals of Ablation in metastatic CRC • Prolong survival • No proven benefit (yet) • Treat unresectable disease • Makes us feel like we did something • In combination with resection • To clear positive or narrow margin • To ablate residual tumor
Hepatic Resection of Colorectal MetastasesStrategies to increase resectability: Ablation • Experience still limited in downstaging process • No good studies to confer benefit or increase resectability rates • Wallace et al Surgery 1999 – Cryotherapy with surgery. Two-thirds recurrence by 2 years. • Pawlik et al ASO 2003 – combined RFA with surgical resection in 172 patients. Median f/u 21 months – 56% recurrence • RFA with less EBL, shorter LOS, but longer ablation times, higher recurrence for large lesions (> 3 cm)
Hepatic Resection of Colorectal MetastasesStrategies to increase resectability • Conclusions • Be aggressive in your approach • Consider preoperative adjuvant chemotherapy to increase resectability rates • Utilize ablative techniques as a complement to surgical resection when able to completely eradicate viable tumor