Tretinoin and the Prevention of Keratinocyte Carcinoma (Basal and Squamous Cell Carcinoma of the Skin): A Veterans Affairs Randomized Chemoprevention Trial

Abstract

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.

Guidelines of care for the management of basal cell carcinoma

“…Topical and oral retinoids are not recommended for reducing risk for subsequent BCC in patients with a history of BCC. Topical retinoids have not been found to reduce the incidence of keratinocyte cancers or actinic keratosis in those with a history of a keratinocyte cancer 123 or the incidence of BCC in those with Gorlin-Goltz syndrome. 124 In addition, topical retinoids used for prolonged periods were associated with increased mortality in a single study, although some investigators have discounted this result as spurious.…”

“…[116][117][118][119]123,[125][126][127][128][129][130][131][132][133][134][135][136][137][138][139][140][141] …”

Retinoids and rexinoids in cancer prevention: from laboratory to clinic

“…Premalignant skin lesions, including actinic keratosis and HPV-induced tumors are frequently treated with retinoids [44]. Patients at high-risk for skin cancer because of genetic disposition (xeroderma pigmentosum), organ transplantation or history of multiple tumors, may be treated with etretinate or acitretin for 6 months [45].…”

Psoriasis Therapies and the Risk of Cutaneous Malignancy

“…Topical regimens also do not appear efficacious in preventing malignancy. Recently, a randomized controlled trial of 1,131 patients from the Veterans Affairs system with a 5-year history of 2 or more NMSCs showed no statistically significant benefit of 0.1% topical tretinoin in precluding development of invasive NMSC or actinic keratosis 35 .…”