Cost-Effectiveness of Hepatic Metastasectomy in Patients With Metastatic Colorectal Carcinoma: A State-Transition Monte Carlo Decision Analysis

ObjectiveTo evaluate the cost-effectiveness of hepatic resection (“metastasectomy”) in patients with metachronous liver metastases from colorectal carcinoma (CRC), and to investigate the impact of operative and follow-up strategies on outcomes, cost, and cost-effectiveness. Summary Background DataThere is substantial evidence that resection of CRC liver metastases can result in long-term survival in some patients. However, several unresolved issues are difficult to address using currently available clinical data. These include the appropriate threshold for resection, whether to perform repeat resection, and the relative cost-effectiveness of the procedure(s). MethodsThe authors developed a state-transition Monte Carlo decision model to evaluate the (societal) cost-effectiveness of hepatic metastasectomy in patients with metachronous CRC liver metastases. The model tracks the presence, number, size, location, growth, detection, and removal of up to 15 individual metastases in each patient. Survival, quality of life, and cost are predicted on the basis of disease extent. Imaging and surgery affect outcomes via detection and removal of individual metastases. Several patient management strategies were developed and compared with respect to cost, effectiveness, and incremental cost-effectiveness ($/quality-adjusted life year [QALY]). A reference strategy in which metastasectomy is not offered and imaging is not performed for the purpose of assessing resectability or operative planning (“no-surgery” strategy) was included for comparison. Extensive sensitivity analysis was performed to evaluate the impact of alternative model assumptions on results. ResultsA strategy permitting resection of up to six metastases and one repeat resection, with CT follow-up every 6 months, resulted in a gain of 2.63 QALYs relative to the no-test/no-treat strategy, at an incremental cost of $18,100/QALY. When additional surgical strategies were considered, the incremental cost-effectiveness ratio (ICER; relative to the next least effective strategy) of the six metastases, one repeat, 6-month strategy was $31,700/QALY. Across a range of model assumptions, more aggressive treatment strategies (i.e., resection of more metastases, resection of recurrent metastases) were superior to less aggressive strategies and had ICERs below $35,000/QALY. Findings were insensitive to changes in most model parameters but somewhat sensitive to changes in surgery and treatment costs. ConclusionsHepatic metastasectomy is a cost-effective option for selected patients with metachronous CRC metastases limited to the liver. When considering metastasectomy, more aggressive approaches are generally preferred to less aggressive approaches. Overall, surgeons should be encouraged to consider resection for all patients whose metastases can technically be removed.

[1]  T. Strohmeyer,et al.  The distribution of metastases of different primary tumors in the liver. , 2008, Liver.

[2]  D. S. Lind,et al.  Formal hepatic resection of colorectal liver metastases. Ploidy and prognosis. , 1992, Annals of surgery.

[3]  D. Ilstrup,et al.  Perioperative Blood Transfusion and Determinants of Survival After Liver Resection for Metastatic Colorectal Carcinoma , 1992, Annals of surgery.

[4]  A. Altendorf-Hofmann,et al.  Indicators of prognosis after hepatic resection for colorectal secondaries. , 1991, Surgery.

[5]  J R Beck,et al.  Markov Models in Medical Decision Making , 1993, Medical decision making : an international journal of the Society for Medical Decision Making.

[6]  D. Ilstrup,et al.  The Natural History of Hepatic Metastases from Colorectal Cancer: A Comparison with Resective Treatment , 1984, Annals of surgery.

[7]  C. Hagen,et al.  The distribution of liver metastases from colonic cancer , 1985, Virchows Archiv A.

[8]  M. Castagneto,et al.  The systematic use of operative ultrasound for detection of liver metastases during colorectal surgery , 1987, World Journal of Surgery.

[9]  S. Kawasaki,et al.  Calculation of child and adult standard liver volume for liver transplantation , 1995, Hepatology.

[10]  O. Garden,et al.  The use of operative ultrasound in surgery of primary liver tumors , 1987, World Journal of Surgery.

[11]  J. Ranstam,et al.  Pattern of recurrence in liver resection for colorectal secondaries , 1987, World Journal of Surgery.

[12]  G. Parker,et al.  Intraoperative Ultrasound of the Liver Affects Operative Decision Making , 1989, Annals of surgery.

[13]  S. Pauker,et al.  The Markov Process in Medical Prognosis , 1983, Medical decision making : an international journal of the Society for Medical Decision Making.

[14]  A Morabito,et al.  One hundred patients with hepatic metastases from colorectal cancer treated by resection: Analysis of prognostic determinants , 1991, The British journal of surgery.

[15]  P. Sakornpant,et al.  Major hepatic resection. , 1974, Journal of the Medical Association of Thailand = Chotmaihet thangphaet.

[16]  T. Starzl,et al.  Experience in hepatic resection for metastatic colorectal cancer: analysis of clinical and pathologic risk factors. , 1994, Surgery.

[17]  L H Blumgart,et al.  Treatment of colorectal cancer: hepatic metastasis. , 1996, Seminars in surgical oncology.

[18]  M. Weinstein,et al.  Recommendations of the Panel on Cost-effectiveness in Health and Medicine. , 1996, JAMA.

[19]  O. Matsui,et al.  Liver metastases from colorectal cancers: detection with CT during arterial portography. , 1987, Radiology.

[20]  B. Cady,et al.  Surgical therapy for recurrent liver metastases from colorectal cancer. , 1990, Archives of surgery.

[21]  M. Weinstein,et al.  The role of cost-effectiveness analysis in health and medicine. Panel on Cost-Effectiveness in Health and Medicine. , 1996, JAMA.

[22]  G J Marks,et al.  Intraoperative ultrasound of the liver. An important adjunctive tool for decision making in the operating room. , 1987, Annals of surgery.

[23]  R. Adkins,et al.  Major Hepatic Resection , 1981, Southern medical journal.

[24]  N Urban,et al.  Stage, age, comorbidity, and direct costs of colon, prostate, and breast cancer care. , 1995, Journal of the National Cancer Institute.

[25]  W. Longmire,et al.  Major hepatic resection. A 25-year experience. , 1983, Annals of surgery.

[26]  B. Nordlinger,et al.  Survival benefit of repeat liver resections for recurrent colorectal metastases: 143 cases. Association Francaise de Chirurgie. , 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  D. Elias,et al.  MRI of Liver Metastases from Colorectal Cancer vs. CT during Arterial Portography , 1993, Journal of computer assisted tomography.

[28]  T. Starzl,et al.  Liver resection for metastatic colorectal cancer. , 1986, Surgery.

[29]  B. V. Van Beers,et al.  Detection and segmental location of malignant hepatic tumors: comparison of ferumoxides-enhanced gradient-echo and T2-weighted spin-echo MR imaging. , 1997, AJR. American journal of roentgenology.

[30]  M. Reiser,et al.  Detection of hepatic masses in patients with carcinoma: comparative sensitivities of sonography, CT, and MR imaging. , 1991, AJR. American journal of roentgenology.

[31]  K. Shirouzu,et al.  Intraoperative ultrasonography in screening for liver metastases from colorectal cancer: comparative accuracy with traditional procedures. , 1987, Surgery.

[32]  Noriyuki Moriyama,et al.  The use of operative ultrasound as an aid to liver resection in patients with hepatocellular carcinoma , 1987, World Journal of Surgery.

[33]  M C Weinstein,et al.  Recommendations for reporting cost-effectiveness analyses. Panel on Cost-Effectiveness in Health and Medicine. , 1996, JAMA.

[34]  D. Ilstrup,et al.  Resection of hepatic metastases from colorectal cancer. , 1984, Archives of surgery.

[35]  B. Nordlinger,et al.  Survival benefit of repeat liver resection for recurrent colorectal metastases: 143 cases. , 1997, Wiadomosci lekarskie.

[36]  C. McArdle,et al.  Occult hepatic metastases in colorectal carcinoma , 1986, The British journal of surgery.

[37]  A. Altendorf-Hofmann,et al.  Factors influencing the natural history of colorectal liver metastases , 1994, The Lancet.

[38]  T. Ravikumar,et al.  Prospective comparison of preoperative imaging and intraoperative ultrasonography in the detection of liver tumors , 1989, Surgery.

[39]  F. R. Watson,et al.  Factors influencing survival in patients with untreated hepatic metastases. , 1968, Surgery, gynecology & obstetrics.

[40]  Shohachi Suzuki,et al.  Resection of Liver Metastases of Colorectal Carcinoma , 1997, World Journal of Surgery.

[41]  J. Foster Survival after liver resection for secondary tumors. , 1978, American journal of surgery.

[42]  R. Doci,et al.  Hepatic resections for colorectal metastases: The italian multicenter experience , 1991, Journal of surgical oncology. Supplement.

[43]  B. Nordlinger,et al.  Hepatic Resection for Colorectal Liver Metastases: Influence on Survival of Preoperative Factors and Surgery for Recurrences in 80 Patients , 1987, Annals of surgery.

[44]  K. Abrams,et al.  Quality of life and survival with continuous hepatic-artery floxuridine infusion for colorectal liver metastases , 1994, The Lancet.

[45]  P. Robinson,et al.  Hepatic lesion detection: comparison of MR imaging after the administration of superparamagnetic iron oxide with dual-phase CT by using alternative-free response receiver operating characteristic analysis. , 1999, Radiology.

[46]  Peter Schlag,et al.  Resection of the liver for colorectal carcinoma metastases , 1988, Diseases of the colon and rectum.

[47]  J. Aldrete,et al.  Hepatic Resection of Metastasis from Colorectal Carcinoma: Morbidity, Mortality, and Pattern of Recurrence , 1989, Annals of surgery.

[48]  R. Doci,et al.  Patterns of Failure Following Surgical Resection of Colorectal Cancer Liver Metastases: Rationale for a Multimodal Approach , 1987, Annals of surgery.

[49]  R. Klein,et al.  The Beaver Dam Health Outcomes study , 1993, Medical decision making : an international journal of the Society for Medical Decision Making.

[50]  L H Blumgart,et al.  A retrospective study of the natural history of patients with liver metastases from colorectal cancer. , 1976, Clinical oncology.

[51]  Milton C. Weinstein,et al.  The role of cost-effectiveness analysis in health and medicine. Panel on Cost-Effectiveness in Health and Medicine. , 1996 .

[52]  C. Glover,et al.  Relation between tumor size, quality of life, and survival in patients with colorectal liver metastases. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[53]  A. Altendorf-Hofmann,et al.  Hepatic metastases from colorectal carcinoma: Impact of surgical resection on the natural history , 1990, The British journal of surgery.

[54]  J. Daly,et al.  Hepatic resection for metastases of the colon and rectum. , 1986, Surgery, gynecology & obstetrics.

[55]  B. Cady,et al.  Experience with colorectal carcinoma metastatic to the liver. , 1989, The Surgical clinics of North America.

[56]  C. Balch,et al.  A multifactorial analysis of prognostic factors in patients with liver metastases from colorectal carcinoma. , 1983, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[57]  C. McArdle,et al.  Growth rate of hepatic metastases in colorectal carcinoma , 1988, The British journal of surgery.

[58]  J M Rubin,et al.  Comparisons of dynamic infusion and delayed computed tomography, intraoperative ultrasound, and palpation in the diagnosis of liver metastases. , 1993, American journal of surgery.

[59]  J. Heiken,et al.  Detection of focal hepatic masses: prospective evaluation with CT, delayed CT, CT during arterial portography, and MR imaging. , 1989, Radiology.

[60]  B. Langer,et al.  Examination of patient selection and outcome for hepatic resection for metastatic disease. , 1987, Surgery, gynecology & obstetrics.

[61]  K. Hughes,et al.  Resection of the liver for colorectal carcinoma metastases: a multi-institutional study of patterns of recurrence. , 1986, Surgery.

[62]  J. Figueras,et al.  Helical CT versus CT arterial portography in the detection of hepatic metastasis of colorectal carcinoma. , 1998, AJR. American journal of roentgenology.

[63]  S Bengmark,et al.  The natural history of primary and secondary malignant tumors of the liver I. The prognosis for patients with hepatic metastases from colonic and rectal carcinoma by laparotomy , 1969, Cancer.

[64]  N. Kemeny,et al.  Management of metastatic cancer to the liver. , 1989, Advances in surgery.

[65]  Y. Lee,et al.  Liver metastases from colorectal carcinoma: incidence, resectability, and survival results. , 1994, The American surgeon.

[66]  P. Jönsson,et al.  Natural history of patients with untreated liver metastases from colorectal cancer. , 1981, American journal of surgery.

[67]  B. Rubinsky,et al.  Society of Gastrointestinal Radiologists Roscoe E. Miller Award. Monitoring hepatic cryosurgery with sonography. , 1986, AJR. American journal of roentgenology.

[68]  P. Schlag,et al.  Resection of liver metastases in colorectal cancer--competitive analysis of treatment results in synchronous versus metachronous metastases. , 1990, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[69]  K. Hughes Resection of the liver for colorectal carcinoma metastases: a multi-institutional study of indications for resection. Registry of Hepatic Metastases. , 1988, Surgery.

[70]  Patient selection and factors affecting results following resection for hepatic metastases from colorectal carcinoma. , 1991, International surgery.

[71]  G. Mangiante,et al.  Repeated hepatic resection. , 1987, International surgery.

[72]  N. Petrelli,et al.  A prospective evaluation of hepatic resection for colorectal carcinoma metastases to the liver: Gastrointestinal Tumor Study Group Protocol 6584. , 1991, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[73]  A. Rogatko,et al.  The Influence of Intraoperative Hypotension and Perioperative Blood Transfusion on Disease‐free Survival in Patients with Complete Resection of Golorectal Liver Metastases , 1991, Annals of surgery.

[74]  J. Fortner,et al.  Multivariate Analysis of a Personal Series of 247 Consecutive Patients with Liver Metastases from Colorectal Cancer: I. Treatment by Hepatic Resection , 1984, Annals of surgery.

[75]  L H Blumgart,et al.  Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. , 1999, Annals of surgery.

[76]  R. Doci,et al.  Patterns of failure following surgical resection of colorectal cancer liver metastases: rationale for a multimodal approach. , 1988, Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer.

[77]  M. Choti,et al.  Portal-phase contrast-enhanced helical CT for the detection of malignant hepatic tumors: sensitivity based on comparison with intraoperative and pathologic findings. , 1996, AJR. American journal of roentgenology.

[78]  N. Petrelli,et al.  Morbidity and survival of liver resection for colorectal adenocarcinoma , 1991, Diseases of the colon and rectum.

[79]  P. gordon,et al.  Hepatic resection for colorectal liver metastases. , 1995, The American surgeon.

[80]  R. J. Marshall,et al.  Factors affecting survival in patients presenting with synchronous hepatic metastases from colorectal cancer: A clinical and computer analysis , 1985, The British journal of surgery.

[81]  N. Petrelli,et al.  Hepatic resection for isolated metastasis from colorectal carcinoma. , 1985, American journal of surgery.

[82]  R. Goslin,et al.  Factors influencing survival in patients with hepatic metastases from adenocarcinoma of the colon or rectum , 1982, Diseases of the colon and rectum.

[83]  G. White,et al.  Does intraoperative hepatic ultrasonography change surgical decision making during liver resection? , 1994, American journal of surgery.

[84]  M. Adson Resection of liver metastases—When is it worthwhile? , 1987, World Journal of Surgery.

[85]  L. Dionne,et al.  The pattern of blood‐borne metastasis from carcinoma of rectum , 1965, Cancer.

[86]  J R Beck,et al.  A convenient approximation of life expectancy (the "DEALE"). I. Validation of the method. , 1982, The American journal of medicine.

[87]  Jerome P. Kassirer,et al.  A Convenient Approximation of Life Expectancy , 1992 .

[88]  Milton C. Weinstein,et al.  Recommendations for Reporting Cost-effectiveness Analyses , 1996 .

[89]  J R Beck,et al.  A convenient approximation of life expectancy (the "DEALE"). II. Use in medical decision-making. , 1982, The American journal of medicine.

[90]  J. Boey,et al.  Carcinoma of the colon and rectum with liver involvement. , 1981, Surgery, gynecology & obstetrics.

[91]  M. Bernardino,et al.  Hepatic tumors: comparison of CT during arterial portography, delayed CT, and MR imaging for preoperative evaluation. , 1989, Radiology.

[92]  J. Fleshman,et al.  Liver resection for colorectal metastases. , 2004, Annals of the Royal College of Surgeons of England.

[93]  B. Nordlinger,et al.  Repeat liver resection for recurrent colorectal metastases , 1993, The British journal of surgery.