The Surgical Management of Colorectal Metastases

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11th July 2017 Bowel Cancer UK The Surgical Management of Colorectal Metastases Ben Cresswell MD(Res) FRCS Consultant HPB Surgeon The Basingstoke Hepatobiliary Unit United Kingdom

Surgical Management of Colorectal Metastases The problem in context Selection for liver resection Strategies to improve operability Timing of liver resection Extra-hepatic disease

Bowel Cancer Facts Lifetime Risk Males - 1 in 14 Females - 1 in 19

Bowel Cancer Facts Despite the rising incidence, survival is also increasing 50% Improvement in 10 year survival since 1970s Quality of surgery Quality of staging Improved chemotherapy Better treatment of metastatic disease

Colorectal Liver Metastases 15-20% present with synchronous metastases 1 ~50% will develop liver metastases 2 ~30% the liver is the only site of metastatic disease 3 1. Fong Y, Kemeny N, Paty P et al. Semin Surg Oncol 1996; 12:219-51. 2. Steele G, Ravikumar TS. Ann Surg 1989; 210:127-38. 3. Weiss L, Grundmann E, Torhorst J et al. J Pathol 1986; 150:195-203.

CRLM - Natural History % Survival Untreated 1 Year 2 Years 5 Years Wagner et al 1984 Strangl et al 1994 Rougier et al 1995 74 42 3 46 14 2 60 30 3 Median Survival 6-9 Months Few Survive to 5 Years

Resection of CRLM 5 Year Survival - 40-50% 90 Day Mortality - ~1%

CRLM - Improving Survival Better Detection Better Selection Accurate Systemic Staging Accurate Liver Specific Staging Appropriate Adjunctive Therapies Strategies to Improve Resectability High Quality Precision Surgery

Detection of Liver Metastases Follow-up practice is highly variable - often nihilistic Cochrane Review 2007 (8 Studies) 5 Yr Survival benefit to intensive F/U Similar number of recurrences, but detected significantly earlier 5 Yr Survival benefit with regular liver imaging Significantly more surgical interventions with curative intent with intensive F/U

Follow-up After Colorectal Surgery Trial Need to intensively Follow-up 12-20 Pts to detect 1 curable recurrence Primrose et al 2014

The Importance of Liver Staging Extent of Liver Involvement Define Anatomy Before commencing any adjuvant treatment Disappearing lesions Cystic transformation of lesions

Detailed Pre-treatment Imaging Changed stage 56% Reduced intra-hepatic recurrence (at diff site) 48 vs 65% Reduced rate of re-resection 13 vs 25% Knowles et al 2012

Biopsy has NO Role for Resectable Lesions Biopsy is less sensitive and specific than high quality imaging 1 Biopsy reduces matched 5 Yr survival due to seeding 2 1 Cresswell et al 2009 2 Jones et al 2005

Selection - 1999 Unilobar disease <5cm Maximum size <4 Metastases >1cm Margin Absence of Extra-hepatic Disease Age

Selection - 1999 Unilobar disease <5cm Maximum size <4 Metastases >1cm Margin Absence of Extra-hepatic Disease Age Only 10% would be resectable

Selection - 2017 The ability to preserve a sufficient volume of liver parenchyma with adequate inflow and outflow structures Complete excision of lesions (1mm margin) 1 Liver only disease or the presence of treatable extrahepatic disease General fitness for surgery 1 Hamady et al 2014

Selection - 2017 The ability to preserve a sufficient volume of liver parenchyma with adequate inflow and outflow structures Complete excision of lesions (1mm margin) 1 Liver only disease or the presence of treatable extrahepatic disease General fitness for surgery >50% Resectable 1 Hamady et al 2014

Define the Anatomy

Define the Anatomy

Strategies for Improving Resectability Neoadjuvant Chemotherapy Portal Vein Embolisation Staged Resection ALPPS Procedure Resection & Ablation Topical Neo-adj Treatment (Chemo / Radioembolisation)

Conversion Chemotherapy Neoadjuvant Chemotherapy 16% Inoperable Patients Liver Resection 39% 5 Yr Survival

Conversion Chemotherapy

Conversion Chemotherapy Folprecht et al 2005

Effect on Bilobar Disease

Effect on Bilobar Disease

Effect on Large / Poorly Located Disease

Effect on Large / Poorly Located Disease

Chemotherapy Associated Liver Injury

Chemotherapy Associated Liver Injury Increased Infection Increased Hepatic Insufficiency More Difficult Surgery - Increased Blood Loss Karoui et al 2006 Majority of effect in 3-4 cycles Increased morbidity after 5 cycles Limit duration of Chemotherapy to achieve required effect

Timing of Liver Surgery

Timing of Liver Surgery Metachronous Disease Straight to resection

Timing of Liver Surgery Inoperable Disease Straight to Conversion Chemotherapy 6 Cycles Re-stage after Cycle 5

Timing of Liver Surgery - Synchronous Non-critically Located Peri-operative chemotherapy 1 Critically Located Straight to surgery Liver before primary 2 1 In Press 2017 2 Welsh et al 2016

Timing of Liver Surgery Disappearing Lesions Non - Critically Located - Trial of Time off chemo Critically Located - 6 weeks after stopping chemo

Extra-hepatic Metastatic Disease - Dogma

Extra-hepatic Metastatic Disease - Dogma Improved chemotherapeutic options Better understanding of tumour biology Safer surgery and better preoperative care

The Basingstoke Ethos To offer resection if all tumour sites can be treated (resected / ablated) with acceptable risks of morbidity

Overall Survival

Peritoneal Disease

An Approach - Select the Winners Accurate diagnosis and staging CT / MRI / PET / Laparoscopy Assess tumour biology Trial of time Trial of chemotherapy Histology of primary Plan treatment for all sites of disease Resection (+/- HIPEC) Ablation DXT

Take Home Messages Very few people are definitely inoperable - please refer everyone Get good quality liver imaging up-front - this is our road map NO BIOPSIES - please Limited extra-hepatic disease is no contra-indication

NHS Patients linda.hillman@hhft.nhs.uk 01256 313566 Private Patients amanda.thomas@bmihealthcare.co.uk 01256 377701