Summary Of Evidence

Significance

Evidence Of Benefit

SUMMARY OF EVIDENCE

Nonmelanoma skin cancer:

Evidence suggests that reduction of exposure to ultraviolet (UV) radiation will reduce the incidence of nonmelanoma skin cancer. Sun exposure can be reduced by changing patterns of outdoor activities to reduce time of exposure to high-intensity UV radiation, and by using adequate amounts of sufficiently protective sunscreens or wearing protective clothing when exposed to sunlight.[1]

Levels of Evidence for preceding statement: 1b,3aii,5

Evidence obtained from at least one well-designed and conducted randomized controlled trial with a generally accepted intermediate endpoint

Evidence obtained from well-designed and conducted cohort or case-control analytic studies, preferably from more than one center or research group, with a cancer incidence endpoint

Opinions of respected authorities based on clinical experience or reports of expert committees

Evidence suggests that avoidance of sunburns, especially in childhood and adolescence, may reduce the incidence of cutaneous melanoma. Sunburn can be avoided by changing patterns of outdoor activities to reduce time of exposure to high-intensity UV radiation, by wearing protective clothing when exposed to sunlight, and by using adequate amounts of sufficiently protective sunscreen. Sunscreen is not a substitute for avoidance of sun exposure.[1,2]

Levels of Evidence for preceding statement: 3aii,4aii,5

Evidence obtained from well-designed and conducted cohort or case-control analytic studies, preferably from more than one center or research group, with a cancer incidence endpoint

Ecologic (descriptive) studies with a cancer incidence endpoint

Opinions of respected authorities based on clinical experience or reports of expert committees

References:

1. Vainio H, Miller AB, Bianchini F: An international evaluation of the cancer-preventive potential of sunscreens. International Journal of Cancer 88(5): 838-842.
2. Autier P, Dore JF, et al, for the European Organization for Research and Treatment of Cancer Melanoma Cooperative Group: Sunscreen use, wearing clothes, and number of nevi in 6- to 7-year-old European children. Journal of the National Cancer Institute 90(24): 1873-1880, 1998.

SIGNIFICANCE

The visible evidence of susceptibility to skin cancer (skin type, precancerous lesions) and of sun-induced skin damage (sunburn, solar keratoses), and the ability of an individual to modify sun exposure provide the basis for implementation of programs for the primary prevention of skin cancer.

References:

1. American Cancer Society: Cancer Facts and Figures-1999. Atlanta, Ga: American Cancer Society, 1999.
2. Greenlee RT, Hill-Harmon MB, Murray T, et al.: Cancer statistics, 2001. CA: A Cancer Journal for Clinicians 51(1): 15-36, 2001.
3. Koh HK: Cutaneous melanoma. New England Journal of Medicine 325(3): 171-182, 1991.
4. Preston DS, Stern RS: Nonmelanoma cancers of the skin. New England Journal of Medicine 327(23): 1649-1662, 1992.
5. Hall HI, Miller DR, Rogers JD, et al.: Update on the incidence and mortality from melanoma in the United States. Journal of the American Academy of Dermatology 40(1):35-42, 1999.
6. English DR, Armstrong BK, Kricker A, et al.: Case-control study of sun exposure and squamous cell carcinoma of the skin. International Journal of Cancer 77(3): 347-353, 1998.

EVIDENCE OF BENEFIT

It is not known, however, if reduction of exposure to UV radiation through use of sunscreens and/or protective clothing or through limitation of exposure time can reduce the incidence of nonmelanoma skin cancer in humans. One study has shown that regular sunscreen use can reduce the incidence of solar keratoses (precursors of squamous cell carcinoma) and increase remissions of existing lesions.[3] In Australia, 588 persons 40 years and older who attended a free skin cancer screening clinic and had 1 to 30 solar keratoses were enrolled in a randomized, controlled trial assessing the effect that the regular use of sunscreen (Sun Protection Factor 17) could have on solar keratoses; 431 persons completed the study. Persons in the sunscreen group developed significantly fewer new lesions and had significantly more remissions of existing lesions than persons in the base-cream group. Amount of sunscreen used was related to development of new lesions and remission of existing lesions in the sunscreen group; no such effect was observed in the base-cream group.

The relationship between UV radiation exposure and cutaneous melanoma is less clear. Rather than cumulative sun exposure, it is intermittent acute sun exposure that seems to be more damaging; such exposures in childhood or adolescence may be particularly important.[4] Results from a collaborative European case-control study and one animal study, however, suggest that sunscreens that protect against sunburn may not protect against UV radiation-associated cutaneous melanoma.[5,6] Non-modifiable host factors, such as propensity to burn, a large number of benign melanocytic nevi, and atypical nevi may also increase the risk of developing cutaneous melanoma.[4]

Several groups have conducted studies to learn more about possible intervention strategies for reduction of exposure to UV radiation. The best weapon seems to be education about the risks associated with sun exposure and sunburn and education about sun protection strategies.[7,8] Although long-term "reminders" regarding recommendations for sun protection may have had some impact on reducing sun exposure in individuals who had been treated for nonmelanoma skin cancer, it was the educational intervention at the time of treatment that seemed to have had the greatest impact - a time when an individual may have recognized his or her susceptibility to skin cancer.[7] Even in this high-risk group, it was difficult for many individuals to maintain sun protective behaviors. A community skin cancer screening study found that although regular use of sunscreens was not related to personal or family history of skin cancer, it was more common among persons who perceived themselves to be at moderate or high risk of developing melanoma.[8] Sun protective strategies may include avoiding sun exposure at times of the day when the exposure is more intense and wearing clothing that protects skin from sun exposure.

Self-examination for skin pigmentary characteristics associated with melanoma (e.g., freckling status) may be a useful way to identify individuals at increased risk of developing melanoma.[9] Skin type (propensity to burn after sun exposure, tanning ability), alone or with other physical characteristics such as hair color, has been used as a measure of sun sensitivity in epidemiologic studies.[10]

The efficacy of chemopreventive agents (isotretinoin, beta carotene) has been assessed in individuals at increased risk of developing nonmelanoma skin cancer. High-dose isotretinoin was found to prevent new skin cancers in individuals with xeroderma pigmentosum.[11] A randomized clinical trial of long-term treatment with isotretinoin in individuals previously treated for basal cell carcinoma, however, showed that such treatment did not prevent the occurrence of new basal cell carcinomas but did produce side effects characteristic of isotretinoin treatment.[12,13] A randomized clinical trial of long-term treatment with beta carotene in individuals previously treated for nonmelanoma skin cancer showed no benefit for the occurrence of new nonmelanoma skin cancers.[14] For both of these 2 trials, it is not known if treatment would benefit individuals at high-risk (sun-damaged skin) who have not yet developed skin cancer or if longer follow-up would show a long-term effect in the prevention of subsequent skin cancers.

A multicenter, double-blind, randomized, placebo-controlled trial of 1312 patients with a history of basal-cell or squamous-cell skin cancer and a mean follow-up of 6.4 years showed that 200 ug selenium (in brewer's yeast tablet) did not have a significant effect on the primary endpoint of the development of basal-cell or squamous-cell carcinoma of the skin.[15]

References:

1. Preston DS, Stern RS: Nonmelanoma cancers of the skin. New England Journal of Medicine 327(23): 1649-1662, 1992.
2. English DR, Armstrong BK, Kricker A, et al.: Case-control study of sun exposure and squamous cell carcinoma of the skin. International Journal of Cancer 77(3): 347-353, 1998.
3. Thompson SC, Jolley D, Marks R: Reduction of solar keratoses by regular sunscreen use. New England Journal of Medicine 329(16): 1147-1151, 1993.
4. Koh HK: Cutaneous melanoma. New England Journal of Medicine 325(3): 171-182, 1991.
5. Autier P, Dore JF, Schifflers E, et al.: Melanoma and use of sunscreens: an EORTC case-control study in Germany, Belgium and France. International Journal of Cancer 61(6): 749-755, 1995.
6. Wolf P, Donawho CK, Kripke ML: Effect of sunscreens on UV radiation-induced enhancement of melanoma growth in mice. Journal of the National Cancer Institute 86(2): 99-105, 1994.
7. Robinson JK: Compensation strategies in sun protection behaviors by a population with nonmelanoma skin cancer. Preventive Medicine 21(6): 754-765, 1992.
8. Berwick M, Fine JA, Bolognia JL: Sun exposure and sunscreen use following a community skin cancer screening. Preventive Medicine 21(3): 302-310, 1992.
9. Gruber SB, Roush GC, Barnhill RL: Sensitivity and specificity of self-examination for cutaneous malignant melanoma risk factors. American Journal of Preventive Medicine 9(1): 50-54, 1993.
10. Weinstock MA: Assessment of sun sensitivity by questionnaire: validity of items and formulation of a prediction rule. Journal of Clinical Epidemiology 45(5): 547-552, 1992.
11. Kraemer KH, DiGiovanna JJ, Moshell AN, et al.: Prevention of skin cancer in xeroderma pigmentosum with the use of oral isotretinoin. New England Journal of Medicine 318(25): 1633-1637, 1988.
12. The Isotretinoin-Basal Cell Carcinomas Study Group, Tangrea JA, Edwards BK, et al.: Long-term therapy with low-dose isotretinoin for prevention of basal cell carcinoma: a multicenter clinical trial. Journal of the National Cancer Institute 84(5): 328-332, 1992.
13. The Isotretinoin-Basal Cell Carcinoma Study Group, Tangrea JA, Adrianza E, et al.: Clinical and laboratory adverse effects associated with long-term, low-dose isotretinoin: incidence and risk factors. Cancer Epidemiology, Biomarkers and Prevention 2(4): 375-380, 1993.
14. The Skin Cancer Prevention Study Group, Greenberg ER, Baron JA, et al.: A clinical trial of beta carotene to prevent basal-cell and squamous-cell cancers of the skin. New England Journal of Medicine 323(12): 789-795, 1990.
15. Clark LC, Combs GF Jr,Turnbull BW, et al.: Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin: a randomized controlled trial. JAMA: Journal of the American Medical Association 276(24): 1957-1963, 1996.

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