Tretinoin and the prevention of keratinocyte carcinoma (Basal and squamous cell carcinoma of the skin): a veterans affairs randomized chemoprevention trial

J Invest Dermatol. 2012 Jun;132(6):1583-90. doi: 10.1038/jid.2011.483. Epub 2012 Feb 9.


Keratinocyte carcinoma (KC) is the most common cancer in the United States, with no proven means for prevention other than systemic retinoids, which have significant toxicity, and sunscreen. Topical tretinoin has been used for KC chemoprevention, although this use is unproven. Hence, we conducted the randomized Veterans Affairs Topical Tretinoin Chemoprevention Trial of high-dose topical tretinoin for KC prevention. We randomized 1,131 patients to topical 0.1% tretinoin or a matching vehicle control for 1.5-5.5 years. The primary outcomes were time to development of new basal cell carcinoma (BCC) and new invasive squamous cell carcinoma (SCC) on the face or ears. The effects were not significant (P=0.3 for BCC and P=0.4 for SCC). The proportions of the tretinoin and control groups who developed a BCC at 5 years were 53 and 54% and an invasive SCC at 5 years were 28 and 31%. These differences (95% confidence intervals) were: for BCC, 1.0% (-6.5, 8.6%); for SCC, 3.6% (-3.1, 10.3%). No differences were observed in any cancer-related end points or in actinic keratosis counts. The only quality of life difference was worse symptoms in the tretinoin group at 12 months after randomization. This trial in high-risk patients demonstrates that high-dose topical tretinoin is ineffective at reducing risk of KCs.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Topical
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Carcinoma, Basal Cell / epidemiology
  • Carcinoma, Basal Cell / prevention & control*
  • Carcinoma, Squamous Cell / epidemiology
  • Carcinoma, Squamous Cell / prevention & control*
  • Female
  • Humans
  • Keratinocytes / drug effects*
  • Male
  • Middle Aged
  • Quality of Health Care
  • Risk Factors
  • Skin Neoplasms / epidemiology
  • Skin Neoplasms / prevention & control*
  • Tretinoin / administration & dosage*
  • Tretinoin / adverse effects
  • Veterans / statistics & numerical data


  • Antineoplastic Agents
  • Tretinoin