Dr Adam Bartlett. General Surgeon Senior Lecturer University of Auckland Auckland City Hospital

Transcription

1 Dr Adam Bartlett General Surgeon Senior Lecturer University of Auckland Auckland City Hospital 11:05-11:15 Hepatic Metastectomy is Associated with Improved Survival

2 Where is everyone?

3 Hepatic Metastectomy is Associated with Improved Survival Adam Bartlett PhD, FRACS Department of Surgery, University of Auckland New Zealand Liver Transplant Unit, Auckland City Hospital HPB/UGI Unit, Department of General Surgery, Auckland City Hospital

4 Counting the cost of cancer surgery Advanced caner that would previously been declared inoperable are increasingly coming into the hands of surgeons Surgery is not necessarily more effective than chemotherpay The responsiveness to chemotherapy has provided an opportunity to re-consider surgery Whether the chemotherapy or surgery are the most important it is not possible to determine The burden of care and cost to the patient and family increase exponentially with increasing complexity

5 So much for that! She plots the course, from diagnosis to death, of a woman with abdominal mesothelioma in present-day America. Fourteen months after being given a 1-year expectation of life, her doctors run out of options and the family runs out of money. The oncologist comforts her bankrupt husband saying we ve probably extended her life a good three months. The bitter irony of good strikes the spouse, but seems lost on the doctor. Shriver L. So Much for That. Harper Collins: New York, 2010.

6 Is more treatment better? Veronesi et al conclusively found that radical mastectomy was not associated with increased survival (N Eng J Med 1981) Second- look laparotomy for colorectal cancer was found to increase the burden of care without extending survival (JAMA 1994) Patients with pleural mesothelioma live a little longer and somewhat better if radical surgery is not performed (Lancet Oncol 2011) The assumption that more treatment must be better treatment has not stood up to the fair test in those instances.

7 Liver metastases from CRCa Liver Metastases (50% of patients) Resectable 20% to 25% Non-resectable 75% to 80% Size Location Number Downsizing tumour Increasing liver remnant Survival Benefit 30% to 60% at 5 years 15% at 10 years Resectable 10% to 20% Leonard GD, et al. J Clin Oncol. 2005;23:

8 Resection of CRCa liver metastases 5-Year Survival in selected Reports (n 100) Study Last Year Included Span, Years Patients, N 5-Year OS, % Adson Registry* Jamison Nordlinger* Gayowski Scheele Jenkins Kato* Fong Choti Bramhall Wei Abdalla Fernandez Pawlik* Adam* Figueras *Patients included from multiple institutions (vs single-institution series).

9 538 patients with colorectal liver metastases 247 underwent liver resection and 291 had palliative chemotherapy 7.8% of non-operated patients survived for 5 years compared to 32.9% of the liver resection group patients are probably not directly comparable because those patients who did not undergo liver surgery due to distribution of disease or fitness had, by definition, biologically aggressive disease or a weak host and their survival would therefore be ex-pected to be worse

10 Principal fear Insert slide of blood loss ++++.the operative records described in brief and controlled terms what were apparently uneventful lobectomies for patients whose anesthesia records, in contrast document transfusion of enormous quantities of blood, with several episodes of cardiac arrest and massive resuscitation efforts. Foster and Berman, 1977

11 Liver resection and mortality Over the decades, postoperative mortality rate has decreased 1,2,3 Figure 3. Postoperative mortality rate of liver resection over the decades Postoperative mortality 20% 18% 16% 14% 12% 10% 8% 6% 4% 2% 0% Savage AP, et al Annals of Surgery, 1991;214(6):689-95; 2. Dimick JB, et al. J Am Coll Surg. 2004;199(1): Virani S, et al. J Am Coll Surg. 2007;204(6):

12 The liver ain t no tomato

13 Joining the dots

14 Survival after hepatic resection has improved over time Lower operative mortality ~ 1% with experienced hepatobiliary surgeons Improved patient selection CT, MRI, PET, PET/CT Improved surgical techniques IOUS, PVE, Thermal ablation More frequent and better perioperative chemotherapy Conventional, immunomodulatory Increased rates of repeat hepatectomy following recurrence

15 Traditional selection criteria: Challenged Traditional criteria 3 metastases Unilobar disease Metastases <5 cm Metachronous lesions Dukes A or B primary Contemporary view Poorer prognosis with >3 lesions Bi-lobar disease not a contraindication Poorer prognosis with lesions >5 cm Synchronous lesions not a contraindication Dukes C have worse prognosis but may still be potentially curable >1 cm Resection margin Microscopically clear margin acceptable No extra-hepatic disease Patients <65 years Exceptions - resectable pulmonary metastases, hepatic recurrence, diaphragmatic invasion Co-morbidity more important

16 New Criteria defining Resectability of CRCa liver metastases Ro treatment is feasible with either resection ± ablation Vascular inflow, outflow and biliary drainage can be preserved Sufficient future liver remnant (>20% of TLV) No extra-hepatic tumour except direct invasion of diaphragm local recurrence - resectable pulmonary metastases Abdalla EK, et al. Ann Surg Oncol. 2006;13: Pawlik TM, et al. J Gastrointest Surg. 2007;11:

17 Concept of adequate functional liver mass Quantity (FLR) Quality Functional liver mass Or both together

18 Accepted future liver remnant volume sflr = Remnant liver volume Standard liver volume 20% Normal liver parenchyma 30% Chemotherapy induced liver injury 40% Chronic liver disease (Child-Pugh A)

19 Typical spread of common cancers

20 Hepatic resection for other liver metastases Annuals of Surgery 2006; 244(4)

21 Breast cancer liver metastases (BCLM) Isolated liver metastases rare (2-12%) 1,2, Treatment with chemotherapy Median survival 8-25 months 1,2 5-yr survival 8-12% 1,2 Treatment intent is palliative 1. Er O, et al. Cancer J. 2008;14(1): Pentheroudakis G, et al. Breast Cancer Res Treat. 2006;97(3)

22 Figure 1. Overall survival and time to progression of 500 patients with breast cancer liver metastases treated with chemotherapy 4 2 years Pentheroudakis G, et al Breast Cancer Res Treat. 2006;97(3):

23 Quorum diagram Potentially relevant citations identified n = 1705 Abstracts excluded (n = 1193) Manuscripts identified describing patients with non-colorectal and nonneuroendocrine liver metastases n = 512 Manuscripts meeting study criteria n = 33 Manuscripts excluded that did not include patients with liver metastases from breast cancer n = 479 Manuscripts found from searching references n = 10 Final number of manuscripts meeting study criteria n = 43 Bartlett et al, in press

24 Results - survival Median survival 36 months months 1-yr survival 90% % 3-yr survival 56% 31-79% 5-yr survival 37% 11-61% Bartlett et al, in press

25 Results - complications Morbidity Mortality 20% 0.7%

26 n= % Survival at 36 months Postoperative mortality Non Surgical Treatment Surgical Treatment Independent predictors of Survival RR = 3.04 (p<0.0001) Hepatic resection Bone metastases not treated Nodal status of primary Number of cycles of chemotherapy

27 Ablation Percutaneous ethanol injection (PEI) Cryotherapy Microwave coagulation therapy (MCT) Laser induced thermotherapy (LITT) Radiofrequency ablation (RFA) Microwave ablation (MWA) Nano-knife

28 Liver directed therapies Femoral artery puncture

29 Summary All cancer treatments harm patients. To be effective, benefit must exceed harm by a measurable and useful margin. Multimodality treatments multiply harm and make it impossible to see the signal from the noise. Definition of resectability has changed however the evidence of effectiveness is lacking. Hepatic resection can be performed with low morbidity & mortality but one needs to be mindful of the social and other costs of cancer treatment. Biological understanding of cancers imperative to predict likelihood of success Multi-disciplinary patient selection and management paramount

30 Conclusion In select patients, the resection of liver metastases may be associated with a genuine survival benefit.

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