Melanoma accounts for the majority of skin cancer deaths worldwide and has dramatically increased in incidence over the past halfcentury. 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.
Over 55,000 white adults in the United States are expected to develop invasive cutaneous malignant melanoma in 2004, and 7,900 patients will die from metastatic disease within the next year. The estimated lifetime risk for melanoma is currently 1 out of 68 Americans, and this number is expected to rise to 1 in 50 by the year 2010. Risk factors including greater occupational and recreational sun exposure have resulted in an increased incidence of melanoma over the past 50 years, although earlier detection and treatment of thinner lesions have contributed to improved patient survival, particularly in younger individuals.[3,4]
The most striking differences in melanoma incidence and mortality occur in individuals over age 65, although modest differences in age-specific incidence and mortality are notable in those over age 50. Older individuals are both more likely to acquire and to die from melanoma, and the elderly should therefore be a primary target for secondary melanoma prevention, ie, early detection and screening to reduce melanoma mortality. Treatment options in the elderly may also be limited due to decreased inability to tolerate medication side effects or toxicity, comorbid medical conditions, increased likelihood of drug interactions, and potential exclusion from clinical trials based on age eligibility criteria.
Melanoma Incidence and Mortality in the Elderly
Early clinical detection of malignant melanoma has the greatest impact on prolonged survival and potential eradication of disease. Earlier diagnosis and treatment of thinner cutaneous melanomas has contributed to a decreased case-based fatality rate in the United States over the past 50 years, despite an overall increase in melanoma incidence.[5,6] Risk factors for development of melanoma include fair skin type, strong family history of melanoma, significant sun exposure (particularly blistering sunburns), the presence of numerous and/or clinically atypical moles, and importantly, older age.
The reasons for the increasing melanoma incidence have yet to be fully defined; it remains controversial whether increasing melanoma incidence is real or simply reflects improved detection of earlier, thinner lesions. For example, in a recent analysis of the Surveillance, Epidemiology, and End Results (SEER) program from 1973 to 1997, the incidence of thin melanomas (< 1 mm depth) increased significantly in all age groups except for men under age 40. Most importantly, this study showed that rates of thick melanomas (≥ 4 mm) have increased significantly only in males aged 60 years and older.
Additional analyses of the SEER mortality (1969-1999) and incidence (1973-1999) databases has yielded notable results regarding the effect of age on melanoma risk and outcome. Analyses were age-adjusted and rates were expressed as deaths per 100,000 and standardized to the 2000 US population.[ 8,9] Data were analyzed separately for white men and women in the following age groups, 20-44, 45-64, and 65+ years. Trends were analyzed separately for each of the six sex/age groups and overall. All age-specific trends and differences between men and women were significant at P < .01 (Figure 1).
Overall, melanoma mortality rates rose from 2.0 per 100,000 in 1969 to 3.0 in 1999, but with striking differences by age and sex. Mortality rates rose 19% in middle-aged women (45- 64 years, 2.6 to 3.1 per 100,000) and 66% in middle-aged men. Most alarming, mortality rates increased 157% in older men (7.5 to 19.3 per 100,000), more than threefold greater than the increase for older women. Incidence data generally paralleled mortality data for the same period, revealing a threefold increase among middle-aged men (13.5 to 40.5 per 100,000) and a nearly fivefold increase in older men (18.8 to 91.9 per 100,000) but less than a doubling for younger men (6.8 to 11.6 per 100,000). Incidence also increased for women, with the same pattern of greater increases in older age groups but less strikingly than in men.
This analysis also yielded important differences in tumor thickness and histology by gender and age. Median tumor- thickness measurements were as follows: 0.54 mm for younger women, 0.64 mm for older women, 0.64 mm for younger men, and 0.67 mm for older men. For all histologic subtypes other than lentigo maligna melanoma, men 50 years of age and older (compared with other age/sex groups) were most likely to be diagnosed with thick (≥ 2.0 mm) tumors. In contrast, younger women had fewer thick melanomas in all histologic subtypes.
Among men age 50 and above, 19% of all melanomas were ≥ 2 mm, more than double the 8% rate among younger women. Women ≥ 50 years old had thicker nodular melanomas than women under age 50 (median: 2.29 vs 1.79 mm). Likewise, men ≥ age 50 had thicker nodular melanomas compared to women less than age 50 (median: 2.39 vs 2.04 mm). Among men and women ≥ age 50, nodular melanoma greater than 2 mm comprised 60% and 57% of all nodular melanomas vs 57% and 45% for men and women less than age 50. These age- and gender-based differences in tumor depth and histogenetic subtype emphasize the need for early detection efforts aimed at the elderly population and older men in particular.
Malignant melanoma may arise de novo or from a precursor melanocytic nevus. A changing nevus is the most important risk factor for melanoma, and variation in size, shape, or color of the preexisting nevus, or onset of bleeding, pain, or pruritus within a mole is noted by over 80% of melanoma patients at the time of diagnosis.[ 11] Precursor lesions include congenital nevi (particularly the giant or "bathing trunk" type), common nevi, clinically atypical (or dysplastic) nevi, and melanoma in situ (lentigo maligna, superficial spreading melanoma in situ, and acral lentiginous melanoma in situ).
Although most patients with primary melanoma report preexisting pigmented lesions, the actual percentage of melanomas confirmed histologically to arise from a preexisting nevus is unclear. Most studies suggest that only about one-third of melanomas arise from a precursor nevus (common, dysplastic, or congenital), although the percentage may actually be higher (≥ 50%) due to possible histologic obliteration of the underlying nevus by deeper melanomas.[12-14]
Elderly patients tend to have fewer nevi in association with their melanomas, likely related to differences in melanoma subtype prevalence, ie, fewer superficial spreading melanomas relative to other histogenetic types in older individuals.[15,16] It has also been suggested that more melanomas arise de novo with increasing age. However, the risk for tranformation of a single nevus into melanoma may be greater with age in part due to declining nevus counts in the older population. Regardless of whether a melanoma arises de novo or from a preexisting nevus, patients and practitioners will often recognize it as a "changing mole," and certain clinical features may aid in prompt and accurate diagnosis.
Physician and patient education regarding the warning signs of early melanoma has been promoted in the United States with the use of the "ABCD" criteria for a changing mole, which includes asymmetry ("A"), border- notching ("B"), color variegation ("C") with black, brown, red, blue, or white hues, and diameter ("D") greater than 6 mm (commonly referred to as greater than the size of a pencil eraser) or any noted growth of a preexisting pigmented lesion. Lesions exhibiting these features should be considered potential melanomas, although severely dysplastic nevi may be difficult to distinguish clinically.
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