We developed a state-transition model to assess melanoma disease progression with time and used it to estimate the impact and value of various melanoma screening programs. We found that 1-time melanoma screening by dermatologists in the US general population at age 50 years and screening of siblings of patients with melanoma every 2 years have cost-effectiveness ratios of $10 100/QALY gained and $35 500/QALY gained, respectively. These ratios are comparable to those for other types of cancer screening, including breast, cervical, and colorectal cancers, all of which are recommended by the US Preventive Services Task Force ().29
If screening costs could be reduced below the base case estimate of $41 per screening, screening would be even more cost-effective.
Cost-effectiveness of Cancer Screening Programs and US Preventive Services Task Force Ratings
Cost-effectiveness analysis is particularly useful when randomized controlled trials cannot be done because of ethical or logistic considerations. In the case of melanoma, the low overall disease prevalence and incidence would require more than 360 000 study participants followed up for 10 years to identify statistically significant differences in the outcome of screening. Cost-effectiveness analysis is most often used when decisions are being made in the absence of randomized trials with mortality end points and when the best available data can be combined from numerous sources to inform policy. Such analyses have been used to guide clinical decision making in colon cancer screening, breast cancer screening, and human immunodeficiency virus disease management, among others.28,30,31
Using this method, interventions in the United States are generally considered cost-effective at less than $50 000/QALY gained or less than $100 000/QALY gained.32,33
Several previous studies have estimated the cost-effectiveness of melanoma screening. Freedberg et al13
estimated a cost-effectiveness ratio of $39 600/YLS for 1-time screening in a population at high risk. That study was limited to 1-time screening, was applied in a younger population, and did not account for increased progression and recurrence of melanoma. Beddingfield34
estimated a cost-effectiveness ratio of $220 700/YLS for 1-time screening of a white population of all ages at average risk. However, the cost-effectiveness for older patients was much lower, at $28 700/YLS. While this estimate differs from that in the current analysis, owing to differences in defining the higher risk population and screening cost, the policy recommendations are similar. Other cost-effectiveness analyses of melanoma prevention strategies have been done in Australia and Italy. The Australian study, by Girgis et al,35
found the cost-effectiveness of screening every 2 years for melanoma by family practice physicians (60% sensitivity) to be $15 000/YLS for men aged 50 years and $25 800/YLS for women aged 50 years. While these results are similar to those in the current study, this is likely owing to both the increased prevalence and incidence of melanoma in Australia compared with the United States and the lower sensitivity of screening by family practice physicians in their study.35
Cristofolini et al,36
in Italy, evaluated the cost-effectiveness of an educational campaign for early diagnosis of melanoma and did not address screening strategies.
Several US national committees have debated melanoma screening but have not included it in recommended guidelines. The Third United States Preventive Services Task Force in 2001 concluded that “evidence is lacking that skin examination by clinicians is effective in reducing mortality or morbidity from skin cancer,”37 (p44)
but called for studies to help identify patients, especially the elderly, at high risk for melanoma.37
The Institute of Medicine reached similar conclusions in 2000 about general screening recommendations but conceded that “clinicians and patients should continue to be alert to the common signs of skin cancer with a particular emphasis on older white males and on melanoma.”38(p62)
To our knowledge, there are no trials of melanoma screening in the United States, and melanoma screening was not included as part of the National Cancer Institute Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.39
Without conclusive evidence, committees have had to rely on observational evidence that suggests but does not prove the effectiveness of melanoma screening in the detection of thinner melanomas, the main determinant of prognosis.40
This study has several limitations. Although they represent the best available published data, these data were derived from multiple sources. Lead-time and length bias may have a role in survival benefit from earlier diagnosis of melanoma, although sensitivity analyses suggest that these have modest effects on the general policy conclusions of this analysis. The actual rate of melanoma progression is unknown; while this had little effect on 1-time screening, the results of screening every 2 years were sensitive to the progression rate. Although in the base-case analysis our model assumed a constant progression rate of 10% from one stage to another, results of the sensitivity analysis confirmed that varying the progression rate between stages did not affect the conclusions. Because the progression rate for any malignancy is unknown, researchers must make specific assumptions about progression rates to examine the cost-effectiveness of screening strategies. Assumptions similar to ours were used in analyses of the cost-effectiveness of screening for breast and colon cancers.24,41
The comprehensive set of sensitivity analyses varying progression rate in this article provides important insight into the role of the progression rate in assessment of the cost-effectiveness of screening for malignant melanoma ().
Recent evidence also suggests that patients with a family history of melanoma are at increased risk for second primary melanomas.42
While not explicitly modeled in this analysis, to the extent that second primary cases represent a major problem and that the incidence of a second primary melanoma in a patient with melanoma is higher than the incidence of a first primary melanoma in otherwise similar patients, screening programs will be even more cost-effective.42,43
While costs of false-positive results are included in this analysis, quality-of-life decrements are not. Given that false-positive results are observed in only about 1% of persons screened and that a false-positive result provides only a small decrement in overall quality of life, the effect of false-positive results on the quality-adjusted life expectancy of the cohort is minimal. Finally, the model did not account for the detection of nonmelanoma skin cancer, which is approximately 20 times more common than melanoma and shares many of the same risk factors.44
Nonmelanoma skin cancer may be diagnosed in a melanoma screening program, adding both costs and benefits. Because the benefits from detection of these lesions are uncertain and there are insufficient data to quantify them, they were not included. Furthermore, the study by Beddingfield,34
which included costs of non-melanoma skin cancer, reported that, while the cost-effectiveness ratio increased by about 25% ($16 900/YLS), the policy recommendations did not change.
The improvements in life expectancy suggested by the results of this study were moderate because only those individuals who develop melanoma gain a survival benefit from screening. Since the prevalence of melanoma in the United States is low, mean life expectancy improvements across the population were limited. In general, increases in life expectancy as a result of screening are smaller than increases as a result of treatment because all patients receiving treatment have the disease.45
What is the future of melanoma screening? The Institute of Medicine did not endorse screening because of lack of efficacy data, yet there is no ongoing effort to obtain such data in the United States. This study suggests that 1-time screening of the general US population at age 50 years for malignant melanoma is very cost-effective and that screening every 2 years of siblings of patients with melanoma may also be cost-effective, depending on disease progression rates. Either screening programs should be expanded or efforts to perform a definitive efficacy trial should be initiated.