Management of Stage IV Colorectal Cancer: Expanding the Horizon

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1 Management of Stage IV Colorectal Cancer: Expanding the Horizon May Tee, MD, MPH and Jan Franko, MD, PhD MercyOne Surgical Group (Mercy Surgical Affiliates) GI Oncology Conference 2019 March 1, 2019

2 Disclosures None

3 Objectives Surgical management of solitary and oligo-metastatic colorectal cancer (liver, lung, peritoneum) Surgical management of colorectal liver metastases Surgical management of colorectal peritoneal metastases

4 Surgical Metastectomy Liver Metastases Synchronous vs. metachronous Staged vs. concurrent resection with colorectal primary Liver resection Liver directed therapies Transplantation Peritoneal Metastases Cytoreductive curative intent surgery HIPEC (Heated Intraperitoneal Chemotherapy) PIPAC (Pressurized Intraperitoneal Aerosol Chemotherapy)

5 Colorectal Liver Metastases (CLM) Roughly 50% of colorectal cancer cases develop hepatic metastases Resection of colorectal liver metastases has the potential to provide durable cure: 5-Year Survival: 30-40% 10-Year Survival: 20-30% Median Survival: 3-4 years Clinical Epidemiology 2012; 4:

6 Synchronous versus Metachronous Metastases Prognosis of synchronous versus metachronous CLM Synchronous Same time May have more disseminated disease at presentation Metachronous Later time Longer disease free interval may indicate better biology Annals of Surgical Oncology 2006; 14:

7 Surgical Strategies for Synchronous Disease Classic: primary resected then liver disease Reverse: liver resected before primary disease Combined: primary and liver disease resected concurrently No differences in perioperative and overall survival outcomes J Am Coll Surg 2010; 210:

8 Combined Colorectal and Liver Resections J Gastrointestinal Surgery 2015; 19:

9 Resection versus Ablation Borrowed practice from hepatocellular cancer Local recurrence greater with ablation Survival lower with ablation? Annals of Surgery 2004; 239: Archives of Surgery 2008; 143:

10 Parenchymal Sparing versus Anatomic Many advantages Increasing use Equivalent oncologic outcomes (margin status, overall survival, recurrencefree survival) In patients that have recurrent CLM, 5-year survival improved Annals of Surgery 2016; 263:

11 Bilobar Hepatic Metastases Single stage: everything removed in one operation Two stage: usually left removed first then right (+/- portal vein embolization or ligation) Pros and cons to both Generally equivalent if remnant liver adequate British Journal of Surgery 2011; 98:

12 ALPSS Associating liver partition and portal vein ligation for staged hepatectomy LIGRO RCT from Sweden of 97 patients with bilobar CLM ALPPS resection rate 92% compared to 2 stage hepatectomy rate with or without portal vein embolization of 57% No differences in margins, morbidity, mortality Annals of Surgery 2018; 267:

13 HAI Hepatic Arterial Infusion RCT from MSKCC in 1990 s Compared HAI with systemic chemo versus chemo only HAI median survival 72 months compared to 59 months, recurrence free survival 90% compared to 60%, progression free survival 57% versus 42%. N Engl J Med 1999; 341:

14 Recurrent CLM 40% of patient will recur after resection of CLM Recurrence can be: at margin, hepatic, or extrahepatic Re-resection can improve survival but only if technically possible Annals of Surgery 2016; 263: Annals of Surgery 2005; 241:

15 Liver Directed Therapies Percutaneous Ablation Trans-Arterial Chemo- Embolization (TACE) Y-90 Radioembolization

16 Transplant for CLM Landmark observational study from Netherlands 21 patients offered transplant with liver only CLM, resected primary, and 6 weeks of systemic therapy 1 and 5 year survival: 95% and 60% Metastatic / local recurrence developed in 19 of 21 patients after median of 6 months! Annals of Surgery 2013; 257:

17 Cyto Reductive Surgery HIPEC (Hyperthermic Intraperitoneal Chemotherapy) PIPAC (Pressurized Intraperitoneal Aerosol Chemo)

18 HIPEC Dutch protocol for colorectal cancer with carcinomatosis 660 patients studied Perioperative mortality 3% and major morbidity 34% Median length of stay 16 days Median progression free survival: 15 months Overall median survival: 33 months 5-year survival: 31% Annals of Surgical Oncology 2013; 20:

19 PIPAC World Journal of Surgical Oncology 2016; 14:253

20 Summary Metastatic colorectal cancer where surgical extirpation of all disease is possible should be considered for curative resection Early referral to hepatobiliary / surgical oncology is important for all patients with colorectal liver metastases Peritoneal carcinomatosis is not a contraindication to curative intent surgery

21 Thank you MercyOne Surgical Group Surgical Oncology Phone: