Non-melanoma skin cancer (NMSCs) is the most common cancer in America, with over 2 million cases diagnosed annually. Despite the large population affected and resultant burden of disease, no effective chemopreventative strategies have been identified, especially among sun-damaged individuals with existing precancerous skin lesions who are at high risk of developing skin cancer. Actinic keratoses (AKs) are precancerous skin lesions that arise on sun-damaged skin and can progress to NMSCs. The two most widely used topical agents for the treatment of multiple AKs are 5- fluorouracil (5-FU) and imiquimod. Although visits for AKs accounts for over 3.7 million ambulatory care office visits per year in the US and their treatment poses a substantial financial burden to our healthcare system, costing over a billion dollars annually, no studies have compared the effectiveness of the these twp topical field-based therapies. We propose to compare the effectiveness of 5-FU and imiquimod in preventing NMSCs (primary aim) and AKs (secondary aim) using retrospective data from Kaiser Permanente Northern California (KPNC). We also seek to ascertain dose-response curves for each drug over a 5 year follow-up period. One of the unique features of the project is the setting, which allows for ascertainment of effectiveness in a real-world practice environment. KPNC also offers the added advantage of rich electronic databases, with a wealth of information of exposure (detailed pharmacy database), outcome (unique NMSC registry which identified non-reportable skin cancer), and potentially relevant co-variates. The other unique aspect of this proposal is the way in which the retrospective observational data is approached, utilizing novel biostatistical methodologies (point-treatment marginal structural models) to draw casual inference regarding the relationship between exposure and outcome as would be obtained in a clinical trial setting. These newly developed methods have not been previously used in Dermato-epidemiology. The goals of this project align with NIAMS's long-range planning goals of increasing skin related clinical research by performing """"""""comparative effectiveness of therapies, and combination therapy approaches for skin disease treatment."""""""" By accomplishing our study aims, we can help identify the most effective topical agent among high risk individuals for the prevention of the most common cancer in America.

Public Health Relevance

This proposal seeks to analyze existing data in a large healthcare plan to compare two different field-based topical treatments for multiple actinic keratoses in preventing non-melanoma skin cancer and subsequent actinic keratoses. This study is important because no previous studies in real-world setting have determined which of these two agents is better at preventing non-melanoma skin cancer. Identifying the most effective field-treatment for precancerous skin growths may help identify a superior chemopreventative agent for non- melanoma skin cancer.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Small Research Grants (R03)
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Special Emphasis Panel (ZAR1-EHB (M1))
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Baker, Carl
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Kaiser Foundation Research Institute
United States
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Neugebauer, Romain; Levandoski, Katherine A; Zhu, Zheng et al. (2018) A real-world, community-based cohort study comparing the effectiveness of topical fluorouracil versus topical imiquimod for the treatment of actinic keratosis. J Am Acad Dermatol 78:710-716
Storer, Molly; Zhu, Zheng; Sokil, Monika et al. (2017) Community-Based Practice Variations in Topical Treatment of Actinic Keratoses. JAMA Dermatol 153:468-470
Dai, Zhenpeng; Xing, Luzhou; Cerise, Jane et al. (2016) CXCR3 Blockade Inhibits T Cell Migration into the Skin and Prevents Development of Alopecia Areata. J Immunol 197:1089-99
Herrinton, Lisa J; Harrold, Leslie; Salman, Craig et al. (2016) Population Variations in Rheumatoid Arthritis Treatment and Outcomes, Northern California, 1998-2009. Perm J 20:4-12