Screening for cutaneous melanoma

Current data do not support widespread population-based screening for melanoma. While the incidence of melanoma is high, the overall mortality is low, and thus any potential benefit of screening the general population is hard to demonstrate. No randomized controlled trial showing reduction in mortality has ever been completed and, given the expense and time necessary for such a trial, probably will never be completed. The idea of skin screening remains appealing for this common, visible malignancy which is eminently treatable when detected early. Efforts should be focused on populations at particularly high risk of developing melanoma and on those at high risk of death from melanoma once diagnosed. Persons in kindreds of familial melanoma, and persons who have atypical mole syndrome, those who have a prior diagnosis of melanoma, or those who have diagnosed atypical nevi are all reasonable candidates for routine screening, based on lower-level evidence in the absence of randomized clinical trials targeting these groups. Programs targeting persons of low socioeconomic status and targeting white men over the age of 50 could address groups known to beat especially high risk of melanoma mortality.     

Screening and early detection of skin cancer

Skin cancer is the most common type of cancer in the United States. US incidence of malignant melanoma is increasing faster than any other type of cancer. To minimize increasing morbidity and mortality rates, it is imperative that appropriate screening and early detection of skin cancer become more widespread. All physicians who see patients clinically have the potential for detecting skin cancers. The scope of skin cancer as a health-care problem is discussed. Evidence for the effectiveness and necessity of skin cancer screening and early detection is presented. Costs of screening and detection are discussed in relation to impact on treatment costs and overall costs of skin cancer burden. Current methods and recommendations for skin cancer screening and detection are reviewed, especially with regard to individuals and populations that may require more specialized or intensive screening and follow-up. Newer approaches involving instrument-assisted screening and detection of skin cancer are under intense development, and these exciting emerging technologies are reviewed.     

Characteristics associated with early and late melanoma metastases

BACKGROUND:

Differences in risk factors for metastases at different time intervals after treatment have been described in several malignancies; however, to the authors' knowledge, no extensive study examining this issue in melanoma has been conducted to date.

METHODS:

The authors performed a nested case‐control study of patients with melanoma who presented with only local disease. Patients in the case group included 549 patients who developed metastases ≥6 months after surgery. Of these, 320 patients developed metastasis within 3 years after undergoing definitive surgery (early metastases [EM]), and 70 patients developed metastasis ≥8 years after undergoing definitive surgery (late metastases [LM]). For each case, a control patient was chosen who had melanoma but who did not develop metastases in the same interval. Univariate and conditional multivariate logistic regression were used in the analysis of 34 clinical and tumor characteristics.

RESULTS:

Multivariate analysis confirmed previously established risk factors for metastases, such as increasing tumor thickness. In addition, the authors discovered that a personal history of nonmelanoma skin cancer (P = .006) and a history of cancer other than skin cancer (P = .020) also were associated with metastasis. In comparing the 320 EM patients with the 70 LM patients, EM patients were more likely to have thicker lesions (P < .001), ulcerated lesions (P = .016), and a history of nonmelanoma skin cancer (P = .024).

CONCLUSIONS:

In this study, 2 potentially novel risk factors for melanoma metastases were identified, and different profiles of risk factors were constructed for EM versus LM. These differences may be important in future risk identification and stratification for clinical trials and for the management and treatment of patients with melanoma. Cancer 2010. © 2010 American Cancer Society.     

The many unanswered questions related to the German skin cancer screening programme

In 2008, the first nationwide skin cancer screening (SCS) programme in the world was established in Germany. The main reason to implement the SCS programme in Germany was the expected reduction of costs of care due to earlier detection of skin cancer. The aim of this commentary is to raise and discuss several unanswered questions related to the German SCS programme. The evidence of a temporary mortality decline of skin melanoma after SCS in Schleswig-Holstein is lower than previously assumed and the temporary decline may have been caused by other factors than screening (e.g. awareness effects, selection bias, data artifact, and random fluctuation). The evaluation of the nationwide effect of SCS on skin cancer mortality is hampered by birth cohort effects and low quality of the routine cause-of-death statistics. The nationwide skin melanoma mortality did not decrease from 2007 through 2014. The time interval between screenings after a screening without pathological findings is unclear. Appropriate research designs are needed that monitor and evaluate the effect of SCS not only on skin cancer mortality but also on other factors that may help to judge the potential benefits and harms of SCS including aggressiveness of therapy, costs of care, quality of life, and stage-specific incidence rates of skin cancer. Furthermore, SCS may profit from a high-risk strategy instead of population-wide screening and from newer technologies for early detection of skin cancer (e.g. dermoscopy).     

Strategies for improving melanoma education and screening for men age >or= 50 years: findings from the American Academy of Dermatological National Skin Cancer Sreening Program

BACKGROUND: Recently, the Institute of Medicine (2000) and the Third United States Preventive Services Task Force (2001) called for studies to help clinicians identify patients, especially elderly patients, who are at high risk for melanoma. In the current study, the authors sought to identify factors associated with a high yield in skin cancer screening and to explore strategies for improving mass screenings for melanoma. METHODS: The authors analyzed the data base of the 242,374 skin cancer screenings conducted on more than 206,000 Americans who attended the American Academy of Dermatology National Skin Cancer Screening Programs during the period 1992-1994. RESULTS: Ninety-six percent of 3476 screenees with a presumptive diagnosis of melanoma or possible melanoma were contacted, and follow-up records were obtained for 73% of screenees. Of these, 363 screenees had histologically proven melanoma. Middle-aged and older men (age >or= 50 years) comprised only 25% of screenees but comprised 44% of those with a confirmed diagnosis of melanoma. The overall yield of melanoma (the number of confirmed diagnoses per the number of screenees) was 1.5 per 1000 screenings (363 diagnoses of 242,374 screenees) compared with a yield of 2.6 per 1000 screenings among men age >or= 50 years. The yield was improved further for men age >or= 50 years who reported either a changing mole (4.6 per 1000 screenings) or skin types I and II (3.8 per 1000 screenings). The predictive value of a screening diagnosis of melanoma was more than twice as high for men age >or= 50 years with either a changing mole or skin types I and II compared with all other participants. CONCLUSIONS: The yield of mass screening for melanoma would be improved by outreach to middle-aged and older men, with particular focus on men with changing moles or with skin types I and II. Primary care physicians should be attuned to the risk factors among all of their patients but should be alerted in particular to the heightened risk of melanoma for men age >or= 50 years. Formal assessment of the impact of targeted screening on mortality warrants further study.     

Nucleotide excision repair as a marker for susceptibility to tobacco-related cancers: a review of molecular epidemiological studies

DNA repair is a complicated biological process consisting of several distinct pathways that play a central role in maintaining genomic stability. Research on DNA repair and cancer risk is a vital, emerging field that recently has seen rapid advances facilitated by the completion of the Human Genome Project. In this review, we described phenotypic and genotypic markers of nucleotide excision repair (NER) that have been used in molecular epidemiology studies. We summarized the population-based studies to date that have examined the association between DNA repair capacity phenotype and genetic polymorphisms of the NER genes and risk of tobacco-related cancers, including cancers of the lung, head and neck, prostate, bladder, breast, and esophagus. We also included studies of melanoma and nonmelanoma skin cancers because individuals with defective NER, such as patients with xeroderma pigmentosum (XP) are highly susceptible to ultraviolet light (UV)-induced melanoma and nonmelanoma skin cancers. The published data provide emerging evidence that DNA repair capacity may contribute to genetic susceptibility to cancers in the general population. However, many of the studies are limited in terms of the size of the study populations. Furthermore, all published findings are still considered preliminary, the assays used in the studies have yet to be validated, and the results need to be confirmed. Large and well-designed population-based studies are warranted to assess gene-gene and gene-environment interactions and to ultimately determine, which biomarkers of DNA repair capacity are useful for screening high-risk populations for primary prevention and early detection of tobacco-related cancers.     

Increase in skin cancer screening during a community-based randomized intervention trial

Survival from cutaneous melanoma is mainly dependent on the thickness of the lesion at diagnosis. Skin screening may increase detection of thin lesions and hence improve survival. Within a community-based randomized controlled trial of a population screening program for melanoma in Queensland, Australia, 9 communities were randomly assigned to the 3-year intervention and 9 communities to the control group. Skin screening prevalence was monitored by cross-sectional surveys at baseline, 1, 2 and 3 years into the intervention and 2 years later. At baseline, prevalence of whole-body clinical skin examination was similar in intervention and control communities. In intervention communities, the prevalence of whole-body skin examinations increased to 29.2%, an absolute difference of 18% from baseline, with a peak of 34.8% 2 years after baseline, and began to decline again at the end of the intervention period. The largest increases were seen in men and women > or =50 years. Uptake of screening did not differ according to melanoma risk factors; however, the decline in screening was less in participants who reported a number of melanoma risk factors. The prevalence of skin self-examination remained stable during the intervention program. No changes were observed in the control communities. These results indicate that the intervention program significantly increased the prevalence of whole-body clinical skin examinations in intervention communities. Once the intervention program ceased, and particularly after skin clinics ceased, levels of skin screening began to decline. The provision of specialized skin screening clinics may be needed to achieve sufficient screening rates should population based screening for skin cancer be considered.     

Association of surface ultraviolet B radiation levels with melanoma and nonmelanoma skin cancer in United States blacks.

Ultraviolet B (UVB) radiation exposure increases the risk of skin cancer in whites. Motivated by indications that United States geographic variation of relative skin cancer risk in blacks approaches that in whites, we used Poisson regression to estimate the risk of skin cancer in blacks as a function of average annual surface-levels of UVB radiation, measured by Robertson-Berger meters. United States data were used on deaths in 506 state economic areas, 1970-1994, and on incident cases in the nine areas of the Surveillance, Epidemiology, and End Results Program, 1973-1994. For black males, the age-adjusted relative risk of mortality for a 50% increase in UVB radiation was significantly above one for malignant melanoma, 1970-1994 (1.16; 95% confidence interval, 1.02-1.32) and nearly so for nonmelanoma skin cancer, 1970-1981 (1.18; 95% confidence interval, 1.00-1.39), for which the time period was chosen to avoid AIDS-related deaths from Kaposi's sarcoma. However, for black females, the relative risk of mortality was not significantly elevated for either skin cancer, and, for both black males and females, the relative risk of incidence was not significantly elevated for melanoma in the period 1973-1994. Incidence data on nonmelanoma skin cancer were not available. Although the public health implication is uncertain because of the much lower absolute risk of skin cancer in blacks compared with whites, the findings suggest that sunlight exposure increases skin cancer risk in blacks.     

Pr?vention des malignen Melanoms

The incidence of cutaneous melanoma is rising steadily in Germany and worldwide. Primary prevention of melanoma comprises UV protection as the central environmental factor for melanoma development. A significant step forward in secondary melanoma prevention was seen with the inclusion of skin cancer screening in the standard benefits of public health insurances in Germany. Additionally, patients with a high melanoma risk should be examined using dermoscopy and, when indicated, with digital dermoscopic follow-up. This enables the early diagnosis of melanoma at a curable stage.     

Dermoscopy for skin cancer detection

PURPOSE OF REVIEW: The worldwide incidence of melanoma and nonmelanoma skin cancers is increasing alarmingly. The development of new techniques such as dermoscopy leads to a consequent progress in skin cancers screening. The purpose of this review is to highlight recent advances in dermoscopy, reviewing primary research articles published in the last year. RECENT FINDINGS: With the recent standardization of diagnostic procedures obtained by the Consensus Net Meeting on Dermoscopy and the definition of new melanoma-specific criteria, the efficacy in early melanoma diagnosis is improved. Dermoscopy is cost effective, leading to a decreased number of excised benign lesions, and the dermoscopic follow-up allows early detection of melanomas. However, the technique must be performed by experts in order not to miss melanomas. For this reason, instruction in dermoscopy is mandatory. Moreover, computer-aided diagnosis has been tested to be a valid support for physicians. Teledermoscopy is a new tool that allows a second expert opinion to manage atypical lesions. SUMMARY: Dermoscopy opens up a new dimension on clinical morphology of skin lesions. Digital follow-up examinations, computer-aided diagnosis, and teledermoscopy are new facilities that will change the current management of skin cancers in general and melanoma in particular. Dermoscopy in the hands of experienced physicians has higher discriminatory power than naked-eye examination to detect skin cancers.     

Evidenz für ein Hautkrebsscreening

Background

In 2008 Germany was the first country to introduce a nationwide population-based skin cancer screening after a pilot project in Schleswig-Holstein had shown promising results.

Objectives

This article gives an overview of the current evidence for the effectiveness of a German skin cancer screening program.

Material and methods

The number needed to screen was derived from data of the pilot project. The impact of screening on melanoma incidence and mortality was analyzed based on cancer registry data and on mortality statistics from Schleswig-Holstein and adjacent regions.

Results

A malignant tumor of the skin was found in 1 out of 116 screening participants and a melanoma in 1 out of 620. The intensified search for skin cancer resulted in an increase in melanoma incidence during the pilot project and a subsequent decline, as expected. A reduction in melanoma mortality was observed in Schleswig-Holstein but not in any of the adjacent regions.

Conclusion

The current evidence suggests that a population-based skin cancer screening is feasible and effective; however, further research is urgently needed: Open questions concern the benefit-harm relationship of the skin cancer screening, interval carcinomas and cost-effectiveness.     

Increased incidence of melanoma in renal transplantation recipients

BACKGROUND: It is well established that the incidence of nonmelanoma skin carcinoma is increased in renal transplantation recipients. However, existing studies are not in agreement over whether patients who undergo transplantation have an increased risk of melanoma. The objective of this study was to estimate the risk of melanoma among immunosuppressed renal transplantation recipients and to determine whether that risk is associated with patient and transplantation characteristics. METHODS: The authors studied 89,786 patients who underwent renal transplantation between 1988 and 1998 using the United States Renal Data System. Age standardized (to the United States 2000 population) incidence rates for melanoma were computed as diagnoses per 100,000 population and were compared with rates from the Surveillance, Epidemiology, and End Results (SEER) data. Incidence rates also were stratified to examine differences by age and gender. RESULTS: Of the 89,786 patients who underwent transplantation, 246 patients developed melanoma. The age-adjusted incidence rate of melanoma among renal transplantation recipients was 55.9 diagnoses per 100,000 population. This represented an increase in age-adjusted, standardized risk that was 3.6 times greater than the SEER population. Stratified analysis suggested that the risk of melanoma accelerated in male transplantation recipients as age increased, but the risk leveled off with age among female transplantation recipients. Finally, there was a trend for patients who experienced at least 1 acute rejection episode to develop melanoma (odds ratio = 1.34; P = 0.059). CONCLUSIONS: Renal transplantation recipients were nearly 3.6 times more likely to develop melanoma than the general population. Physicians who care for renal transplantation recipients should be vigilant in screening for melanoma.     

Italian Euromelanoma Day Screening Campaign (2005-2007) and the planning of melanoma screening strategies

Although no study has definitively shown that unfocused screening of skin cancer is effective, many campaigns have been organized with the aim of increasing awareness on melanoma risk factors. The objective of this study was to analyse the results of the Skin Cancer Screening Day in Italy during the period 2005-2007, to determine the priorities for melanoma control plans in a Mediterranean country. A total of 5002 patients were screened by dermatologists in 31 cities. Individuals who considered themselves to have many naevi and those with a family history of melanoma showed a higher number of common and atypical naevi. Ten melanomas, 20 basal cell carcinomas and two squamous cell carcinomas were histopathologically confirmed. Our observations provide the following suggestions for melanoma prevention strategies: (a) an unfocused campaign is suitable to inform the public about the importance of self-examination of the skin, but is not useful to identify a larger number of melanomas; and (b) melanoma screening campaigns should focus on a selected population, which meets rigorous risk criteria to maintain higher cost-effectiveness. The financial support to effective melanoma screening programmes could be increased, especially in southern populations where lower levels of self-surveillance and socioeconomic conditions represent risk factors for late identification of melanoma.     

Evaluating the usefulness of self-reported risk factors in a skin cancer screening program

The objective of this study was to describe the risk factor profile of skin cancer screening participants and to determine whether there is an association between the number of skin cancer/melanoma risk factors and the likelihood of diagnosis of a malignant melanoma. Seventy skin cancer screening clinics were held by the Lions Cancer Institute in predominantly rural areas of Western Australia between 1996 and 2003. Participants were self-selected and voluntary, responding to an advertisement seeking people at 'high-risk' of melanoma. The Lions Cancer Institute skin screening clinics targeted participation by individuals with three or more of the established risk factors for skin cancer/melanoma. Questionnaires collecting information on the self-report of nine risk factors were completed by 5950 participants who were screened for melanoma between 1996 and 2003. The number and type of risk factors, and of provisionally diagnosed and histopathologically confirmed malignant melanomas were measured. Of 5950 participants, 18 histopathologically confirmed malignant melanomas were detected. A participant's total number of risk factors showed some association with the provisional melanoma diagnosis given at the time of screening. No relationship, however, was observed between the number of risk factors and a melanoma that was histopathologically confirmed after screening. The risk factor method is effective in selecting a 'high risk' population, but does not seem to have high value in predicting who will be diagnosed with melanoma as a result of screening. Further studies are needed to verify this finding owing to the rarity of melanoma and the small number of confirmed melanomas in this study.     

Melanoma in the older person

Melanoma accounts for the majority of skin cancer deaths worldwide and has dramatically increased in incidence over the past half-century. Despite recent trends showing improved survival, and stabilization of incidence rates in younger Americans, melanoma incidence and mortality continue to rise unabated in older individuals, particularly in men over age 65. Efforts at early clinical detection of melanoma in older individuals should take into account the differences in melanoma subtypes in older individuals, potentially reduced access to medical specialists in this population, as well as comorbidities that may affect ability to undergo treatment for advanced disease. Secondary melanoma prevention should be focused on targeted education to older men and their spouses for early detection and reduction of mortality in this extremely high-risk group.     

Malignant melanoma, breast cancer and other cancers in patients with Parkinson's disease

Previous studies report an atypical cancer pattern among patients with Parkinson's disease. Here, we evaluate the cancer pattern among people diagnosed with Parkinson's disease in an extension of our previous cohort study. For this Danish population-based cohort study, we identified 20,000 people with Parkinson's disease diagnosed in 1977-2006, from the National Danish Hospital Register. Cohort members were followed up for cancer in the Danish Cancer Registry until December 31, 2008, and their incidence rates of cancer were compared to age-, sex- and calendar period-specific rates in the general population as standardized incidence rate ratios (SIRs). In subanalyses, we estimated the risk for cancer among patients with early onset Parkinson's disease and we also compared breast tumor characteristics among women with Parkinson's disease to that of a control group. The overall cancer risk in our cohort was decreased [SIR = 0.86; 95% confidence interval (CI) = 0.83-0.90], as were those for smoking-related (SIR = 0.65; 95% CI = 0.60-0.70) and nonsmoking-related cancers (SIR = 0.79; 95% CI = 0.71-0.86). The cohort had increased risks for malignant melanoma (SIR = 1.41; 95% CI = 1.09-1.80), nonmelanoma skin cancer (SIR = 1.29; 95% CI = 1.18-1.39) and female breast cancer (SIR = 1.17; 95% CI = 1.02-1.34). Among patients with early onset Parkinson's disease, the risk for cancer was comparable to that of the general population. Of breast tumor characteristics, only grade of malignancy differed between Parkinson's disease women and controls. This study confirms a lower cancer risk among people with Parkinson's disease. Increased risks for malignant melanoma, nonmelanoma skin cancer and breast cancer might be due to shared risk factors with Parkinson's disease.     

An ecologic study of cancer mortality rates in Spain with respect to indices of solar UVB irradiance and smoking

There is increasing evidence that vitamin D reduces the risk of many types of cancer. Geographic variations in cancer mortality rates in Spain are apparently linked to variations in solar ultraviolet (UV) irradiances and other factors. Cancer mortality rates for 48 continental Spanish provinces for 1978-1992 were used in linear regression analyses with respect to mortality rates for latitude (an index of solar UVB levels), skin cancer (an index of high cumulative UVB irradiance), melanoma (an index related to solar UV irradiance and several other factors) and lung cancer (an index of cumulative effects of smoking). The 9 cancers with mortality rates significantly correlated with latitude for 1 or both sexes were brain, gastric, melanoma, nonmelanoma skin cancer (NMSC), non-Hodgkin's lymphoma (NHL), pancreatic, pleural, rectal and thyroid cancer. Inverse correlations with latitude were found for laryngeal, lung and uterine corpus cancer. The 17 cancers inversely correlated with NMSC are bladder, brain, breast, colon, esophageal, gallbladder, Hodgkin's lymphoma, lung, melanoma, multiple myeloma, NHL, ovarian, pancreatic, pleural, rectal, thyroid and uterine corpus cancer. The 16 correlated with melanoma are bladder, brain, breast, colon, gallbladder, leukemia, lung, multiple myeloma, NHL, ovarian, pancreatic, pleural, prostate, rectal, renal and uterine corpus cancer. The results for lung cancer were in accordance with the literature. These results provide more support for the UVB/vitamin D/cancer hypothesis and indicate a new way to investigate the role of solar UV irradiance on cancer risk. They also provide more evidence that melanoma and NMSC have different etiologies.     

Screening and Prevention Measures for Melanoma: Is There a Survival Advantage?

Controversy has emerged over the past decades regarding the value and impact of melanoma screening to detect early stage disease for improved prognosis. Those questioning the benefits of prevention efforts base their arguments on the absence of prospective, randomized studies demonstrating decreased melanoma mortality to justify the cost associated with screening and educational campaigns. For those in favor of melanoma screening, the lack of proven survival benefit is not a justification to abandon this approach, but rather a reflection of the lack of resources necessary to conduct a long-term trial. In 2009, the US Preventive Services Task Force (USPSTF)report did not recommend routine primary care screening for the general population given the absence of evidence. However, since the USPSTF report, a series of new studies are available, which support the potential benefit of screening and have the potential to significantly impact current policies regarding skin cancer screening, particularly for melanoma.     

Risk of melanoma among radiologic technologists in the United States

Our study examines the risk of melanoma among medical radiation workers in the U.S. Radiologic Technologists (USRT) study. We evaluated 68,588 white radiologic technologists (78.8% female), certified during 1926-1982, who responded to a baseline questionnaire (1983-1989) and were free of cancer other than nonmelanoma skin at that time. Participants were followed through completion of a second questionnaire (1994-1998). We identified 207 cases, 193 subjects who reported first primary melanoma and 14 decedents with melanoma listed as an underlying or contributory cause of death. We examined risks of occupational radiation exposures using work history information on practices, procedures, and protective measures reported on the baseline questionnaire. Based on Cox proportional hazards regression, melanoma was significantly associated with established risk factors, including constitutional characteristics (skin tone, eye and hair color), personal history of nonmelanoma skin cancer, family history of melanoma and indicators of residential sunlight exposure. Melanoma risk was increased among those who first worked before 1950 (RR = 1.8, 95% CI = 0.6-5.5), particularly among those who worked 5 or more years before 1950 (RR = 2.4; 0.7-8.7; p (trend) for years worked before 1950 = 0.03), when radiation exposures were likely highest. Risk was also modestly elevated among technologists who did not customarily use a lead apron or shield when they first began working (RR = 1.4; 0.8-2.5). Clarifying the possible role of exposure to chronic ionizing radiation in melanoma is likely to require nested case-control studies within occupational cohorts, such as this one, which will assess individual radiation doses, and detailed information about sun exposure, sunburn history and skin susceptibility characteristics.     

Reconstructing skin cancers using animal models

The American Cancer Society estimates that skin cancer is the most prevalent of all cancers with over 2 million cases of nonmelanoma skin cancer each year and 75,000 melanoma cases in 2012. Representative animal cancer models are important for understanding the underlying molecular pathogenesis of these cancers and the development of novel targeted anticancer therapeutics. In this review, we will discuss some of the important animal models that have been useful to identify important pathways involved in basal cell carcinoma, squamous cell carcinoma, and melanoma.