A recent study published in JAMA Dermatology found that a conventional course of fluorouracil to the face and ears substantially reduces surgery for squamous cell carcinoma for 1 year without significantly affecting the corresponding risk for basal cell carcinoma.

The Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial was a randomized, double-blind, placebo-controlled trial of topical fluorouracil for chemoprevention of keratinocyte carcinoma. Participants, recruited from May 2009 to September 2011 from 12 Veterans Affairs medical centers and followed until June 30, 2013, were veterans (n = 932) with a history of at least two keratinocyte carcinomas in the past 5 years. Almost all participants were white males and the median age was 70 years.

Participants applied fluorouracil 5% (n = 468) or vehicle control cream (n = 464) to the face and ears twice daily for two to four weeks upon randomization.

Of 932 participants, 299 developed a basal cell carcinoma end point (95 in year 1) and 108 developed a squamous cell carcinoma end point (25 in year 1) over 4 years (median follow-up, 2.8 years). Over the entire study, there was no difference between treatment groups in time to first keratinocyte, basal cell, or squamous cell carcinoma. During the first year, however, five participants (one percent) in the fluorouracil group developed a squamous cell carcinoma vs 20 (four percent) in the control group, a 75% risk reduction. The 11 percent reduction in basal cell carcinoma risk during year 1 (45 [10 percent] in the fluorouracil group vs 50 [11 percent] in the control group) was not statistically significant, nor was there a significant effect on keratinocyte carcinoma risk. However, a reduction in keratinocyte carcinomas treated with Mohs surgery was observed.