Welcome to the lecture dedicated to the prevention and screening for specific type of skin cancer, cutaneous melanoma. This will be presented in two videos. In these videos, I will present: the burden and public health importance of melanoma, the role of primary prevention, the evidence about screening, an example of a screening program, and issues to be considered for the future. Nowadays, melanoma is considered as a multifactorial disease resulting from interaction between genetic susceptibility and environmental exposure. Ultraviolet radiation is the main causal factor for melanoma. Melanoma affects predominantly fair skin populations and shows of all cancers the greatest variation and risk across countries. Indeed, of 232 cells and new cases of melanoma and of 55,000 deaths from melanoma, which are recorded each year in the world, over three quarters occurred in Europe, North America, Australia, and New Zealand. In these countries, melanoma represent a public health issue for five major reasons. First, melanoma is one, if not the cancer, with the largest increase in incidence over the last 50 years in industrialized countries. Some have called this phenomenon the melanoma epidemic. Second, in countries with the highest incidence, such as Australia, and New Zealand, and Switzerland, melanoma is now one of the five most frequent cancers in both men and women. Third, compared with most cancers, melanoma occurs at a relatively young age with the median age of diagnosis around 55. In high-incidence countries, it is the most frequent cancer in adults below age 30 and the single most frequent in adults below age 40. Fourth, melanoma represent only 10 to 15 percent of all skin cancers. It is by far the deadliest type of skin cancer. Fifth, costs of treatment and management of melanoma are high and growing. Deaths from melanoma leads, on average, about 15 years of life lost, which is as much as cirrhosis and twice the possible life-years lost due to diabetes. The varying importance of melanoma in different countries has of course implications on the prevention efforts dedicated against this cancer. But prevention strategies for melanoma are generally universal and combine primary and secondary prevention. Primary prevention is avoiding overexposure to sun and reducing intermittent sun exposure altogether. Recommendations are to avoid peak irradiance hours, stay in the shade, wear protective clothing including a hat and sunglasses, and, as a last protective measure, to put on sunscreen. But clear emphasis is directed toward protection of children whose skin is most vulnerable to excessive ultraviolet exposure. Awareness of the harmful effects of solar ultraviolet light and sun protection knowledge in the general population has tremendously increased over time so longstanding primary prevention campaigns. The impact of prime prevention against cancer takes time to observe because of the latency period between exposure to carcinogenic agent and cancer development. Melanoma is no exception. It is only recently the decrease in incidence of melanoma in young adults has been reported, first in Australia, then in the US, two countries where primary prevention efforts have been sustained for several decades. These reductions were preceded by the observation over several years of living off melanoma incidents, which is the first interesting sign of a favorable change in trend. A similar pattern of incidence has been observed in other Caucasian populations, and currently decrease in incidents of melanoma is expected in the near future, at least in countries where primary prevention has been conducted for many years. In Thailand, multi-tiers for melanoma has stabilized and started to slightly decrease, first and mostly, in those countries where primary prevention has been sustained over a long time period. We, therefore, have accumulated consistent but indirect evidence from observational studies that changes in sun exposure behavior could lead, in the long run, to a decrease in the melanoma burden. What about screening? The reason for screening is to detect melanoma earlier in its kind of course that would happen with usual care, potentially allowing for earlier and more effective treatment. Melanoma is a good candidate for screening as it is accessible for visual examinations, which is safe, cheap, non-evasive, and well-accepted screening test. Last but not least, screening for melanoma also enables the detection of non-melanoma skin cancer. Total or partial body skin examination can be performed by the patient alone preferably with a mirror to access less visible skin areas by a partner or by a clinician, a dermatologist or primary care physician. Clinical visual examination assesses skin lesions generally using the ABCDE rule, which involves looking for asymmetry, border irregularity, nonuniform color, diameter, and evolution over time. How effective is screening for melanoma in reducing mortality? Currently, there's no evidence from a randomized controlled trial, so the purpose of screening for melanoma leads to a reduction in mortality. A cluster randomized trial was initiated in Australia but was stopped due to lack of funding. This trial intended to compare melanoma mortality after 15 years between communities randomized in two groups. The intervention group received the three-year screening program, couples of promotion of thorough type screening, total body skin examination by a doctor, and open access to skin cancer screening clinics. The other group received usual care. The trial was designed to detect a 20 percent reduction in melanoma mortality between the two groups in the 15 years from the start of the intervention. A similar initiative was recently envisaged in Norway. The European country has the highest incidence of melanoma after Switzerland. The most realistic scenario was to target 40,000 people aged about 50, corresponding to around 200 general practitioners practices, and randomized them between the screening versus the usual care group. However, the statistical power was found insufficient for such a trial to be conclusive even when assuming an expected 30 percent difference in melanoma mortality after 15 years between the two groups. Given the compatibility low-risk rate for melanoma even among high-risk groups conducting inadequately powered randomized controlled trial is challenging. It is unlikely that such a trial for melanoma screening in a general population will be conducted in the near future. What other evidence do we have in absence of randomized control trial? There's one ongoing National Skin Cancer Screening Program. It is in Germany, where 77 percent of all physicians have taken part in a training program and have already screened over 20 million people age 35 or above. The initial implementation of the screening program was decided in November 2007 by the government. A randomized controlled trial was deemed impossible because of the contamination from opportunistic screening. Indeed, most of the evidence came from a pilot program conducted in 2003 and 2004 in the northern Germany states of Schleswig-Holstein during which 26,000 residents were screened with a visual skin examination performed primarily by non-dermatologist. The first ecological studies looking at trends in melanoma mortality over 10 years, that is, the five years preceding and the five years following the intervention indicated a very impressive decrease of 50 percent just in Schleswig-Holstein compared with other areas of Germany and neighboring Denmark. This primary result raised curiosity and interest for many countries. Some epidemiologists and public health specialists considered this five-year result as representing compelling evidence that total body skin examination could be effective for screening. Others were more skeptical mainly for three reasons. First, the mortality benefit occurred very early. The latency period of at least five to seven years is expected before observing any screening impact on cancer mortality. Second, the magnitude of the effect was very large, 50 percent reduction in mortality with the low perception of over 20 percent is unprecedented in cancer screening. Is such a large benefit plausible? Third and last but not least, the ecological design bears several intrinsic limitations for the interpretation of the results. The evaluation of screening programs will indeed be covered in more detail in module eight. The latest trend analysis show that melanoma mortality in Schleswig-Holstein has after 10 years returned with pre-screening level. The drop in mortality was transient. It has mainly been explained by temporal underreporting of melanoma as the underlying cause of deaths. Physicians receive a financial incentive to perform screening also filled the death certificates without being blinded the screening status of subjects. Given the updated weak evidence from the German pilot program, some have questioned the justification of this nationwide program.
