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STANFORD, Calif., Aug, 22 -- For patients with too many facial actinic keratoses to freeze them all off with liquid nitrogen, a face-to-face comparison of three alternative approaches gave the edge to a chemical peel by a nose.

Yet there were no statistically significant outcome differences among the three treatments -- laser removal, chemical peel, and a topical cream -- in a study of 34 high-risk patients, said Susan M. Swetter, M.D., a Stanford dermatologist. Each of the three therapies tested was sufficiently effective to remove lesions and prevent future skin cancer, Dr. Swetter and colleagues reported in the August issue of the Archives of Dermatology.

None quite approached the effectiveness of freezing off the lesions with liquid nitrogen, which is the current standard of care.

The chemical peel stood out from the pack as being better tolerated and having a "markedly lower" rate of new skin cancers after five years. However, the investigators could not be sure of the significance of the latter result because of the study's small sample size, they said.

All patients in the study had either a history of non-melanoma skin cancer or numerous pre-malignant facial actinic keratoses, making them at high risk for new primary skin cancers. They were randomized to one of the three treatment arms for removal of their lesions. Five of the seven patients who declined treatment served as controls. Patients were evaluated every three months for two years and underwent routine surveillance for an additional three years.

The topical cream contained 5% Adrucil (fluorouracil) and the chemical peel consisted of a 30% solution of trichloroacetic acid.

Each treatment significantly reduced the mean lesion count at three months compared with the control group. Laser removal reduced the count by 92% (P=0.03), the acid peel by 89% (P=0.004), and the topical cream by 83% (P=0.008).

However, statistical analysis found no significant difference among the three treatment groups for this outcome (P=0.31).

The current study did not include a test of cryotherapy with liquid nitrogen, but this procedure is 98.8% effective at eliminating actinic keratoses, according to a review article cited by the authors.

In the current study, an intention-to-treat analysis found that new skin cancer incidence rates were also significantly reduced in all treatment groups compared with placebo (P<0.001 for all three). New cancer incidence rates were 1.57 per patient-year in the control group, 0.15 in the laser group, 0.04 in the acid peel group, and 0.21 in the topical cream group.

But as before, no statistically significant differences were found among the three treatments for this outcome (P=0.26).

"Notable, though, is the nearly 40-fold lower rate of subsequent non-melanoma skin cancers in the trichloroacetic acid arm compared with the control population and that significant difference existed between each treatment group and the control," the authors said.

The study did not address adverse events in detail. However, two patients dropped out of the study because they could not tolerate the laser procedure, the authors noted.

"In general, laser resurfacing and chemical peel with trichloroacetic acid are extremely safe procedures associated with limited morbidity," the authors said. "However, if concentrations of trichloroacetic acid greater than 50% are used, scarring may result."

"Subjective assessment of patient preference for the treatment modality revealed less discomfort, fewer patient complaints, and faster time to healing in the trichloroacetic acid arm compared with the laser resurfacing or fluorouracil arms," the authors said, although data on this were not presented.

In addition to the small sample size, another limitation of the study was that the control group consisted of patients who declined treatment. There may have been a bias in the comparisons with the control group because patients were not randomized to the control group, the authors said.

"Despite these limitations, the reductions observed in non-melanoma skin cancer development suggest efficacy in skin cancer prevention for each of these treatments," the authors said.

"Improved patient compliance in the trichloroacetic acid arm, ease of performance in the outpatient setting, and subjective measures of better tolerance for this procedure make it an attractive alternative to repeated courses with topical agents or laser resurfacing," they concluded.

A larger study comparing trichloroacetic acid with laser resurfacing "would help validate the superiority of this resurfacing technique over the carbon dioxide laser" and determine its cost-effectiveness compared with other treatments, they added.

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