Using data from a randomized, double blind, study of the efficacy of retinol or isotretinoin vs. placebo on recurrence of nonmelanoma skin cancer in high-risk subjects, a reanalysis of the original intent to treat analysis was performed in a dose-response format. Cox proportional hazards models describe the relationship between dose quartiles of isotretinoin and retinol use and time to first occurrence of squamous cell carcinoma (SCC) or basal cell carcinoma (BCC) in crude and adjusted models. Neither the isotretinoin nor retinol models showed any significance at any quartile for reduction in first BCC or SCC occurrence. Crude and adjusted retinol models show a statistically significant increase in risk of developing an SCC in the first quartile, whereas only the crude model shows a statistically significant increase in risk in the first quartile of the isotretinoin model. For retinol and SCC, hazard ratios (HRs) for the first quartile were as follows: HR = 2.92, 95% confidence interval (CI) = 1.67-5.10 crude; HR = 1.95, 95% CI = 1.00-3.80 adjusted. For isotretinoin and SCC, HRs for the first quartile were as follows: HR = 2.38, 95% CI = 1.35-4.19 crude; HR = 1.69, 95% CI = 0.87-3.31 adjusted. Test for trend was not significant in any of the models. These analyses confirm the results of the original intent to treat analyses and raise an interesting question related to the potential for increased risk for patients in the first quartile of retinol dose.
