In recent years, the massive economic burden of CRC has finally received increased attention. The societal benefit-cost returns on investments in CRC research and control can be evaluated through cancer economics specific studies . Despite limitations that can arise in cost evaluation, the availability of information on disease costing is crucial, because it forms the basis against which cost reduction strategies and cost-effectiveness analyses can be evaluated. It is possible to determine the opportunity costs to society of CRC, by translating illness and premature death into direct, indirect  and psychosocial costs .
Two approaches have been developed to measure the cost of cancer . The first one, generally known as the cost-of illness approach, tracks cost-generating events and is designed to provide an estimate of the annual aggregate, or prevalent economic impact of disease. A second approach, the incidence approach, is derived from the microeconomic field of project evaluation. It describes the longitudinal pattern of costs incurred by the average patient from the date of diagnosis as well as total lifetime costs of can cer treatment. Data based on this second approach are in demand for economic analysis. It is designed to ensure efficient use of increasingly constrained healthcare resources. Cost evaluations are influenced by many factors including: methods of cost attribution and differences in populations, treatment practices and the existing healthcare delivery patterns.
The overall economic burden of CRC is one of the highest among all neoplasms . The magnitude of CRC prevalence has a significant impact on the total cost, but particularly on the indirect costs of the disease. In the United States, the total direct and indirect costs of CRC have been estimated to be around 5-6 billion dollars . The total cost of CRC for France has been estimated at € 997 million . Social cost structure is reported in Fig. 5. The economic burden of CRC will increase in the future as the population ages and with the adoption of more advanced and expensive diagnostic techniques and treatments.
The longitudinal economic evaluation (using incidence approach) of CRC treatment costs can be phase specific or long term. The phase-specific approach tries to associate direct costs to three postdiagnostic time periods: the initial treatment during the first three months or year following diagnosis; maintenance care or continuing care between initial and terminal treatment (non-survivors) or cessation of care (survivors); and terminal treatment during the final year or six months prior to death. The expected lifetime or total cost is subsequently derived by summing all the cumulative expected medical costs over the entire period.
The distribution of healthcare costs for CRC care is not uniform over the natural history of the disease . The greatest costs are incurred during the first six months following diagnosis, which includes the
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Fig. 5. Cost structure of colorectal cancer for France (1999) (Adapted from )
costs of disease staging, primary treatment and adjunctive therapy. The next most expensive phase is in those patients who develop recurrent disease six months prior to death. The cost profile, given by the survival function for each individual, thus has the appearance of a "U" shaped curve, with the two vertical segments of the U representing initial and terminal phase costs, and the bottom of the U as continuing care costs [198, 199]. Major costs are due to hospitalisation , surgery and chemotherapy , which can be relatively cost-effective [202, 203]. Additional costs include: drugs, physician office visits, and the costs for home healthcare, hospice care and skilled nursing facilities care. Hospitalisation has been suggested to represent 65% and 61% of the lifetime cost of care delivery in colon and rectal cancer respectively .
There is not a monotonic relationship between stage and long-term cost. The costs of treating very early and very late stage cancers seem significantly lower than those of treating cancers in the intermediate stages. Costs are relatively high for stage II and III and lower for in situ, stage I and IV CRC . A screening programme that shifts cases towards earlier stages of diagnosis may produce substantial savings in terms of lower treatment costs. For CRC, initial care and total cancer related costs do not seem to vary according to gender. However, costs do appear to increase in the presence of comorbidities  and for younger patients . Costs seem to be somewhat higher for cancer of the rectum compared with cancer of the colon [198, 206]. This difference has been related to an increased use of new and expensive chemotherapy for the more advanced stages as well as the use of radiotherapy, which can be cost-effective , for stages II and III rectal cancer .
Several studies in North America and Europe addressed treatment cost issues of CRC [208-210]. Initial care costs have been estimated between US $18 000 and $ 22 500 [205, 211-213] and continuous care costs between US $1300 and $1500 per year [205, 213]. Costs are higher on an annual basis among persons with later stages of cancer and shorter survival time . Terminal phase costs have been estimated between US $12 000 and $15 000 [205, 213]. In Canada, the average treatment cost per case for all stages of colon and rectal cancer was estimated to be CAD $ 29 110 and $34 475 respectively . In this research, the average lifetime cost of managing patients with CRC ranged from CAD $20 319 per case for TNM stage I colon cancer to CAD $39 182 per case for stage III rectal cancer. Fig. 6 shows rectal cancer costs.
Research has shown that relatively high and nonuniform frequency of hospital admissions are associ-
ated with CRC [214, 215]. Hospitalisation may be more relevant in patients with advanced disease and worst prognosis . Extensive variation has been reported worldwide in resource utilisation among centres and, thus, costs [217-219]. The study of appropriateness in care settings and resource utilisation patterns may lead to better quality and cost-saving strategies. It is important to stress that higher costs do not necessarily mean higher quality of care.
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