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Rapid Responses: Rapid Responses published:
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Making Molehills of Melanomas
- Deborah J. Merritt (10 August 2005)
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Re: Making Molehills of Melanomas
- Ellen C G Grant (11 August 2005)
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Melanoma Among Women, 25-29
- Deborah J Merritt (11 August 2005)
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Re: Melanoma Among Women, 25-29
- Ellen C G Grant (12 August 2005)
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Re to Welch et al: Real increases of melanoma observed in Europe
- Esther de Vries, Jan-Willem W. Coebergh (30 August 2005)
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Evidence needed for optimal melanoma follow-up methods
- Elizabeth K Delaney, Peter Murchie (4 September 2005)
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Skin Cancer Screening Can Help Save Lives
- Clay J. Cockerell, MD (9 September 2005)
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Deborah J. Merritt, John Deaver Drinko Chair in Law Moritz College of Law, The Ohio State University, 55 West 12th Avenue, Columbus, OH 43210 USA
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Careful studies of disease incidence and the efficacy of early diagnosis make important contributions to medical care. The current study, however, has flaws that seriously constrain its utility. First, while the study is based on adults 65 and older, melanoma is a disease of younger and middle-aged adults. The median age at diagnosis is 53, and it is the most common cancer among women aged 25-29. Although the authors note the age limits of their study, they do not mention the significant epidemiological data on melanoma. Second, as the authors concede, their database includes biopsies for basal and squamous cell carcinomas, as well as for cutaneous manifestations of all forms of systemic disease. Given the prevalence of these non-melanoma conditions in elderly Americans, the irrelevant biopsies undoubtedly predominate in the database. Contrary to the authors' claim, this does not bias their results "to the null." Melanoma is not a condition that can be detected by sampling skin from any part of the body; it is site specific. Indeed, melanoma is relatively uncommon on the face and head--sites where biopsies for other forms of cancer most frequently are performed. It would be very useful to know whether biopsies ordered specifically to rule out melanoma have increased at the same rate as melanoma diagnoses, but this study does not give us that information. Limitations in the data may have forced the authors to include such a large number of irrelevant biopsies in their analysis, but they should be more thoughtful in exploring those limits. Correlating diagnoses of melanoma with biopsies ordered for suspected basal cell carcinoma is not much different from correlating melanoma diagnoses with the prostate biopsies that the authors mention. Finally, mortality rates on melanoma are highly suspect. These rates, like many other disease-specific mortality rates, are drawn from death certificates prepared by individual physicians. Doctors receive no formal training in preparing death certificates and are notoriously poor at recording the cause of death. The attending physician often records the immediate cause of death (heart or kidney failure, sepsis, pneumonia) rather than the underlying disease triggering that final event. Since melanoma kills by metastasizing to other organs, where that cancer becomes the primary focus of concern, doctors may be even less likely to note melanoma as the cause of death. This is particularly true in an elderly population with extensive comorbidity. The relatively constant rate of melanoma mortality most likely reveals the low--and relatively constant--rate at which local physicians record melanoma as an immediate cause of death. It tells us little about how early diagnoses of melanoma might have affected morbidity and mortality in affected patients--particularly if the melanoma is caught before age 65, within the younger group where it is of greatest concern. In the end, this study tells us two things: that diagnoses of stage I and II melanomas are rising among older Americans, and that those diagnoses are rising at the same time that biopsies for all forms of skin disorders are increasing in the same group. Since the latter category is so large, and often unrelated to suspicion or demonstration of melanoma, that correlation does not lend much support to the authors' causal claims. We could also correlate increased diagnosis of melanoma with increased office visits, x-rays, CT scans, pap smears, and a host of other medical procedures. It probably is true that we are diagnosing more melanomas as access to medical care improves. But that fact alone does not help us very much in determining how much of the increased diagnosis is related to increased testing--much less in deciding whether the testing pays off for patients. Despite the significant limits in their study, the authors make sweeping suggestions for health care. The final sentence of their published report announces that "stable mortality in this population suggests that the bulk of these additional cases of melanoma may appear malignant on histology but are nonetheless biologically benign." The lead author has built upon this statement in the press, noting in today's NY Times that the efficacy of melanoma screening is the "million dollar question" and that his study "certainly raises questions about whether we're doing any good" through such screening programs. But this study has little to do with biologic activity and nothing at all to do with screening. The only evidence supporting the authors' suggestion that most stage I and II melanomas are "biologically benign" is the relatively flat mortality rate. To base recommendations on that figure, they at least owed us a thoughtful discussion of limitations in reporting melanoma as a cause of death. The study, meanwhile, includes no data at all on screening. The patients in this study were not screened; they were biopsied, largely for non-melanoma conditions. The only "screening" recommendation we could base on this study would be the nonsensical one that dermatologists could stop biopsying patients with facial lesions highly suspicious for basal cell carcinoma because primary care physicians rarely report melanoma (another disease entirely) as a cause of death. Screening for melanoma is an innocuous component of good medical care. "Screening" means simply that a patient's primary care physician examines the skin--the body's largest organ--along with other organs. Visual screens require no expensive tests and can identify a large number of possible disorders. It is hard to imagine a doctor performing a good physical without examining the skin. Biopsies are more costly, both economically and psychologically. But patients do not lightly allow their doctors to cut off patches of skin. Nor are most doctors eager to cut. Most doctors and patients undergo skin biopsies when there is a strong suspicion of illness--usually a disease other than melanoma. The best way to view the appropriate limits of this study, especially as applied to screening and the possible malignancy of stage I and II melanomas, is to pose the following questions: (1) Do you want your primary care physician to stop looking at your skin--or to stop referring you to a dermatologist if unusual lesions develop? (2) If you had a mole that fit the ABCD criteria for melanoma, would you refuse to have it biopsied because biopsies seem to correlate broadly with diagnoses--i.e., because the biopsy might reveal a melanoma? Would your decision be influenced by the fact that attending physicians rarely list melanoma as a cause of death on formal death certificates? And (3) if the biopsy showed a stage I or II melanoma, would you accept a recommendation just to wait and see if it metastasizes, rather than to have the mole excised with a small margin? I.e., does the fact that doctors rarely report melanoma as a cause of death in older Americans persuade you that the "bulk" of stage I and II melanomas are biologically benign? Competing interests: None declared |
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Ellen C G Grant, physician and medical gynaecologist Kingston-upon-Thames, KT2 7JU, UK
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Deborah Merritt writes that melanoma is the most common cancer among women aged 25-29. Does she know any reasons for this, apart from sunbathing? Competing interests: None declared |
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Deborah J Merritt, John Deaver Drinko Chair in Law Moritz College of Law, The Ohio State University, 55 W 12th Avenue, Columbus, Ohio 43210
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I'm not aware of any studies relating directly to your question, but can offer the following thoughts: First, melanoma may be the most common cancer among this age group in part because women of this age suffer from so few other cancers. By this age, diagnoses of childhood cancers have fallen while those of more typically adult cancers are not yet on the rise. Looking at the "SEER 9" statistics for the United States, for example, the incidence of leukemia is 7.7 per 100,000 among women aged 1- 4, but has dropped to 2.3 per 100,000 among those aged 25-29. Conversely, breast cancer is virtually nonexistent before age 20 and affects only 7.6 per 100,000 among those aged 25-29. Rates for breast cancer begin to rise with the next age groups: 26.8/100,000 among those 30-34 and 61.7/100,000 among those who are 35-39. Set against patterns like these, invasive melanoma becomes the most commonly diagnosed cancer among U.S. women aged 25-29 (9.9 cases per 100,000). But this is only a different way of saying that melanoma displays different epidemiologic patterns than other cancers, which brings us back to your question: Why is this so? Sunbathing may be part of the answer; lots of evidence suggests that sun exposure is linked to melanoma. (Although the link seems somewhat less direct than with other skin cancers, since melanoma often appears on parts of the body that have not themselves been exposed to the sun.) But teenaged men also expose themselves to the sun through sunbathing, sports, and other outdoor activities. It is possible, in fact, that under-30 men receive more sun exposure than under-30 women. They may be more likely to take outdoor jobs (e.g., construction, road work, yard work) than women and to expose more of their torsos while working. Yet the incidence of invasive melanoma among women exceeds that for men through age 44. The male/female incidence rates in the U.S., in fact, show an interesting pattern. Through age 29, the incidence among women is double that among men. E.g., in that 24-29 age group, the incidence among men is 5.5 while that among women is 9.9. Between 30 and 44, the men slowly close the gap. From age 45 on, the incidence of invasive melanoma among men is higher than among women, with the gap widening every 5 years. Starting at age 65, the gap becomes quite marked. The incidence of invasive melanoma among women levels off at that point, moving from 32.6 in the 65-69 group to just 36.3/100,000 in those 85 and over. In men, on the other hand, the incidence climbs markedly, from 67.3 in the 65-69 group to 106.6 in those 85 and older. What could lie behind this pattern? The answer might lie in sun exposure, as you suggest. It could relate to other kinds of life activities or environmental exposures that differ between the sexes. It might suggest a hormonal link, either in promoting or protecting from melanoma. Or it might reflect different patterns of detection: Younger women may be more likely to examine their skin and notice changing moles; doctors may be more likely to notice and remove suspicious moles among older men than women. Undoubtedly there are other sex differences that could explain the pattern. All of these suggestions, though, depend purely upon the recent U.S. incidence rates. A fuller answer would require both clinical and biochemical input. Comparisons with other countries would also be useful. All of the above figures come from the 1998-2002 SEER 9 areas in the U.S. If the sex and age patterns hold across countries, that might suggest a hormonal or other biochemical explanation. Different patterns in different countries might suggest sun exposure, life style, environmental, or detection differences. Or, of course, there can be complex interactions among both biological and environmental/lifestyle factors. Thanks for your inquiry. Perhaps someone else has comments on these epidemiologic questions? Competing interests: None declared |
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Ellen C G Grant, physician and medical gynaecologist Kingston-upon-Thames, KT2 KT2 7JU, UK
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The fact the male/female incidence rates of melanoma in the US are 5.5 for men but 9.9 for women, per 100,000 of those aged 24-29, suggests an effect from prolonged use of oral contraceptives. Several studies have confirmed this connection. In 1968 an increased risk of malignant melanoma with oral contraceptive use was first suggested by Ellerbroek.1 Pigmentation increases in pregnancy due to increases in hormone levels. Walnut Creek Contraceptive Drug Study authors,led by Professor Valerie Beral, reported that women who had used oral contraceptives, particularly long-term users, had higher rates of malignant melanoma and of a past history of skin cancer than those who had never used oral contraceptives in 1977.2 Professor Beral and colleagues also carried out a case control study of 287 young women aged 15-24 years with malignant melanoma and 574 matched controls, in Australia in 1984.3 Ever having used oral contraceptives was not associated with an increased risk of melanoma. However, women with melanoma were more likely to have taken oral contraceptives for long periods of time in the past, the relative risk associated with oral contraceptive use for a total duration of 5 years or longer which had begun at least 10 years before the melanoma was diagnosed being 1.5 (95% confidence interval 1.03 to 2.14) This elevated risk persisted after controlling for the reported hair and skin colour, frequency of moles on the body, place of birth, and measures of sunlight and fluorescent light exposure. Cases were nearly twice as likely as controls to have used hormones to regulate their periods. In the Royal College of General Practitioners' Oral Contraception Study, there were 31 cases of malignant melanoma among ever-users and 27 cases among never-users reported in 1990.4 Women who had used the pill for at least 10 years had an elevated RR of 1.77 (95% CI 0.80-3.90). A case-control study conducted in Italy between 1992 and 1994 did not find a link with hormone use in their study, of 316 women with melanoma and 308 controls.5 The Italian study was not restricted to women in their 20s but also included menopausal women. However, being age older than age 26 at first birth gave an increased odds ratio of 2.69 compared with being younger than age 23 years. Longer OC users may delay their first pregnancy. 1 Ellerbroek WC, Lee JAH. Oral contraceptives and malignant melanoma. JAMA 1968 14; 206:649-50. 2 Beral V, Ramcharan S, Faris R. Malignant melanoma and oral contraceptive use among women in California. Br J Cancer. 1977 ; 36: 804- 9. 3 Beral V, Evans S, Shaw H, Milton G. Oral contraceptive use and malignant melanoma in Australia. Br J Cancer 1984; 50: 681-5. 4 Hannaford PC, Villard-Mackintosh L, Vessey MP, Kay CR. Oral contraceptives and malignant melanoma. Br J Cancer 1991; 63: 430-3. 5 Naldi L, Altieri A, Imberti GL, et al. Cutaneous Malignant Melanoma in Women. Phenotypic Characteristics, Sun Exposure, and Hormonal Factors: A Case-Control Study from Italy. Ann Epidemiol 2005; 15: 545-550. Competing interests: None declared |
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Esther de Vries, Researcher Department of Public Health, Erasmus MC, P.O.Box 1738, 3000 DR Rotterdam, the Netherlands, Jan-Willem W. Coebergh
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Dear Sir, Welch et
al. recently suggested in this journal that the increased incidence of
cutaneous melanoma is a result of overdiagnosis because of increased diagnostic
scrutiny, rather than an increase in the true occurrence (1). They observed that incidence rates
of melanoma among American citizens aged 65 and older was strongly correlated
with biopsy rates and that mortality from melanoma remained stable. We would
like to comment on this from a European perspective. Although there is no doubt
that increased biopsy rates have emerged and contributed to increased detection
of melanomas, there are indications, at least in Europe, that at least part of
the increases of melanoma incidence is true. As a matter of fact, melanoma
mortality rates in Europe were not stable, pointing to real increases in the
incidence of melanoma. In many
European populations, mortality rates of melanoma have been, at least up until
1997, and in the Netherlands also up until 2002 (figures 1,2), continuously and
significantly increasing over time in all age-categories, but especially
amongst elderly men (2, 3). Moreover,
in many populations increases in incidence and mortality have been observed for
up to 5 decades (2), which also argues in favour of at
least part of the increases in melanoma incidence being real: For biopsy rates
to cause the observed linear increases over time, they would have to have been
increasing linearly for decades which we find unlikely. In
conclusion, taking into account the observed increases in mortality from
malignant melanoma in Europe, mainly amongst elderly men, part of the observed
increases in melanoma incidence seems to be ‘real’. References 1. Welch HG, Woloshin S, Schwartz LM. Skin biopsy rates and incidence of melanoma: population based ecological study. Bmj 2005. 2. de
Vries E, Bray F, Coebergh JWW, Parkin DM, ENCR. Changing Epidemiology of malignant cutaneous
melanoma in Europe 1969-1997: rising trends in incidence and mortality, but
recent stabilisations in Western Europe and decreases in Scandinavia. Int J
Cancer 2003, 107, 119-126. 3. de Vries E, Schouten LJ, Coebergh
JWW, Working Group of Cancer Registries. Rising trends in the incidence of and
mortality from cutaneous melanoma in the Netherlands: a Northwest to Southeast
gradient? Eur J Cancer 2003, 39, 1439-1446.
Figure 1: Age-specific incidence rates of cutaneous malignant melanoma
in the Netherlands
Figure 2: Age-specific mortality rates of cutaneous malignant melanoma
in the Netherlands
Competing interests: None declared |
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Elizabeth K Delaney, Academic Fellow Foresterhill Health Centre, Westburn Road, Aberdeen, AB25 2AY, Peter Murchie
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This paper by Welch et al provides us with a thought provoking conclusion and another potential explanation for the worldwide increase in malignant melanoma in caucasian populations. However, whatever the explanation for the observed increase in the incidence of malignant melanoma actually is, it seems unlikely that it will be known anytime in the near future. In the meantime UK health services will be required to cope with increasing numbers of people living with a diagnosis of malignant melanoma. Currently in the UK, following a diagnosis of melanoma most people are followed up regularly in secondary care for up to 10 years. This represents a considerable and increasing demand on the time of specialists, a fact compounded by increasing public awareness of skin cancer, and it seems likely, increasing referrals from primary care. Current follow-up methods are based on opinion rather than good evidence. It seems timeous therefore to consider where and by whom follow- up of melanoma should take place. Could routine melanoma follow-up in primary care by interested general practitioners is one potentially attractive option? Clearly developing an evidence base for the best way to follow-up people with malignant melanoma is a priority. Competing interests: None declared |
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Clay J. Cockerell, MD, President, American Academy of Dermatology Dallas, Texas, USA
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We read the September 2005 article entitled “Skin biopsy rates and incidence of melanoma: population based ecological study” with interest. We are encouraged that the study showed that the mortality rate from melanoma and the incidence of advanced skin cancer has remained consistent despite the increase in the number of melanomas diagnosed. It appears that we have made progress stemming the tide of melanoma. As dermatologists who see people die every day from melanoma, we know that early detection of skin cancer can result in a 95 percent cure rate. Skin cancer screening is a vital tool for detecting melanoma and other skin cancers in their earliest and most treatable stages. These screenings also enable dermatologists to teach people how to check their skin for warning signs and how to be smart in the sun, preventing further skin damage. The American Academy of Dermatology and its members feel so strongly about the value of skin cancer screenings that each year thousands of dermatologists volunteer to provide free skin cancer screenings to the public. In fact, over the past 20 years, more than 1.5 million people have been screened – resulting in the detection of more than 135,500 suspicious lesions, of which more than 15,600 were suspected melanomas. But more needs to be done. The Academy is dedicated to reducing the mortality rate and the incidence of skin cancer. We are exploring innovative ways to motivate people to protect themselves and be vigilant about their skin health. We are committed to continuing to identify suspicious lesions, hoping to catch skin cancer early and saving as many lives as possible. Sincerely, Clay J. Cockerell, M.D. President Competing interests: None declared |
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