837 E D I T O R I A L Counterpoint Cost-Effectiveness of Hepatic Artery Infusion Chemotherapy Boris W. Kuvshinoff, M.D. Division of Surgical Oncology, Ellis Fischel Cancer Center, University of Missouri, Columbia, Missouri. T See referenced original article on pages 882– 8, this issue. Address for reprints: Boris W. Kuvshinoff, M.D., Division of Surgical Oncology, Ellis Fischel Cancer Center, University of Missouri, 115 Business Loop, 70 West, Columbia, MO 65203. Received March 31, 1998; accepted April 6, 1998. © 1998 American Cancer Society he issue of the cost-effective use of health care resources in oncology is an important one, yet there is relatively little written regarding this topic. Consequently, health care administrators and insurers currently are making decisions that influence cancer treatment without sufficient data regarding cost-effectiveness or outcome. In this issue of Cancer, Durand-Zaleski et al. address these issues through the detailed acquisition of hospital and societal treatment costs, quality of life analysis, and survival data.1 The treatment of unresectable liver metastases from colorectal carcinoma is a good example of the difficulties encountered when comparing cancer treatments. Hepatic arterial infusion (HAI) chemotherapy is associated with higher response rates than systemic 5-fluorouracil-based therapy, yet there is conflicting evidence in prospective randomized studies regarding a benefit in survival.2,3 A recent meta-analysis of these studies could not identify a survival advantage for HAI compared with systemic chemotherapy, although there was a survival benefit when studies that included untreated controls were included in the analysis.4 Critics of HAI cite the lack of improved survival together with the inconvenience and risk of an additional laparotomy as reasons why HAI may not be justified. Proponents of HAI argue that the studies conducted thus far lack the design and power to resolve the issue sufficiently. Some of these problems include small sample sizes, treatment crossover, and heterogenous control groups. Clearly, a well designed prospective randomized study comparing HAI and systemic chemotherapy in untreated patients is necessary to settle this controversy. Given the difficulties in showing a survival difference between HAI and systemic chemotherapy, the issues of cost-effectiveness and quality of life have taken on added significance. Durand-Zaleski et al. address both health care and societal costs of HAI and systemic chemotherapy as well as symptom control using data from two randomized trials within the same center.5 Despite the limitations inherent in comparing cost and outcome data from two separate trials, to my knowledge this type of in-depth cost analysis in the treatment of unresectable colorectal liver metastases has not been performed before and the authors should be commended for gathering this information. When total health care costs per patient were analyzed in the study by Durand-Zaleski et al., HAI was the most expensive (£18,762), compared with systemic chemotherapy (£6089) or symptom control 838 CANCER September 1, 1998 / Volume 83 / Number 5 (£2136). The authors take the analysis one step further by determining the cost-effectiveness of each therapy, taking into consideration both survival and quality of life. Comparing HAI with systemic chemotherapy, the health care costs per life-year gained for HAI was £24,604 and the health care costs per normal quality of life-year gained was £24,218. It would appear that the higher total cost of HAI was offset by improvements in both overall and normal quality survival time for the HAI.5 It is especially noteworthy that these treatment costs are well within the range of those reported for other advanced malignancies.6,7 When interpreting this cost analysis, it is important to realize that it was performed within a national health care system, and caution should be taken in applying these results to the U. S. fee-for-service system. Clearly, U. S. health care insurers would not reimburse for a 12.5-day hospital stay for placement of a hepatic artery pump nor the inpatient placement of a venous access port under general anesthesia. The authors recognize this difficulty and provide a sensitivity analysis using a relative value scale for nursing and shorter hospital stays, but these adjustments again should be viewed with a critical eye when extrapolating to other health care delivery systems. Although health care costs can be calculated and are reasonably definable, the interpretation of societal costs for the various treatments is less clear. Societal costs in the current study primarily were based on workdays lost and disability living allowance. The societal cost of HAI was £12,897 per patient compared with £9143 and £8090 for systemic chemotherapy and symptom control, respectively. This difference was present despite a tenfold increase in the median days worked for patients receiving HAI compared with those receiving systemic chemotherapy. Thus, although the majority of HAI patients continued to work, the monetary cost to society still was greater due to more lost workdays as a consequence of their prolonged survival. I agree with the authors that comparing societal cost is problematic, both from a monetary and sociologic perspective. It remains unclear whether the societal costs of various cancer treatments can ever be adequately compared, especially when one considers the complexity of social attitudes toward terminal illness displayed among different cultures and health care systems. The current study would suggest that HAI and systemic chemotherapy are equally cost-effective in providing normal quality survival for health care resources expended. However, it also is evident that the overall health care cost of HAI is considerably more than systemic chemotherapy or supportive care. Health care providers undoubtedly are concerned about issues such as cost-effectiveness with regard to survival and quality of life, but how will third-party payers interpret these data? They may be more concerned with total costs rather than cost-effectiveness. The treatments discussed in the article by DurandZaleski et al. appear to prolong survival but they ultimately are palliative, not curative. For example, from the payor’s point of view HAI is three times more expensive than systemic chemotherapy without a proven significant benefit in survival. From the provider’s point of view, HAI would appear to provide a modest improvement in survival time with acceptable quality of life and reasonable cost-effectiveness. The cost analysis presented by Durand-Zaleski et al. is an important contribution to our understanding of the treatment of unresectable colorectal liver metastases. The cost-effectiveness of both systemic chemotherapy and HAI therapy are well within the range of other commonly utilized palliative cancer treatments. However, caution is needed in extrapolating data from a national health care system to a fee-forservice system. Until survival, quality of life, and cost data can be evaluated from a single prospective randomized study comparing HAI with systemic chemotherapy, the actual cost-effectiveness remains speculative. REFERENCES 1. 2. 3. 4. 5. 6. 7. Durand-Zaleski I, Earlam S, Fordy C, Davies M, Allen-Mersh TG. Cost-effectiveness of systemic and regional chemotherapy for the treatment of patients with unresectable colorectal liver metastases. Cancer 1998;83:882– 8. Kemeny N, Seiter K. Hepatic arterial chemotherapy. In: Cohen AM, Winawer SJ, Friedman MA, Gunderson LL, editors. Cancer of the colon, rectum and anus. New York: McGrawHill, 1995:831– 43. Venook AP. Update on hepatic intra-arterial chemotherapy. Oncology 1997;11:947–70. Meta-Analysis Group in Cancer. Reappraisal of hepatic arterial infusion in the treatment of non-resectable liver metastases from colorectal cancer. J Natl Cancer Inst 1996;88: 252– 8. Allen-Mersh TG, Earlam S, Fordy C, Abrams K, Houghton J. Quality of life and survival with continuous hepatic artery floxuridine infusion for colorectal liver metastases. Lancet 1994;344:1255– 60. Smith TJ, Hillner BE, Desch CE. Efficacy and cost-effectiveness of cancer treatment: rational allocation of resources based on decision analysis. J Natl Cancer Inst 1993;85:1460 – 74. Glimelius B, Hoffman K, Graf W, Haglund U, Nyren O, Pahlman L, et al. Cost-effectiveness of palliative chemotherapy in advanced gastrointestinal malignancies. Ann Oncol 1995;6:267–74.