Aks and occult SCC

February 1, 2007

One in 25 clinically diagnosed AK lesions that were identified by the investigators (board-certified dermatologists) were occult early stage squamous cell carcinomas on histological assessment.

It is a well known fact that actinic keratoses pose a real danger of malignant transformation, if left untreated. Most specialists would agree that diagnosing and treating AK is not very challenging for the experienced dermatologist. But the question may still be asked - how does clinical diagnosis actually correspond with histopathology? And what is the long term safety and efficacy of aminolevulinic acid (ALA)-based photodynamic therapy (PDT) on the lesions?

Clay J. Cockerell, M.D., and Torsten Ehrig, M.D., of Cockerell and Associates Dermatopathology Laboratories, Dallas, and Daniel J. Piacquadio, M.D., and Sydney H. Dromgoole, Ph.D., of Therapeutics Inc., San Diego, strove to address these questions. They conducted a phase IV, multicenter study that was designed to characterize the histopathology of clinically diagnosed AK lesions, and assess the long term safety and efficacy of ALA-based PDT on the lesions.

According to Dr. Piacquadio, "The ability to clinically diagnose AK lesions has been taken for granted for quite some time.

"As the importance of the malignant potential of these lesions has become more evident, the ability to properly diagnose and then treat these lesions has grown in importance," Dr. Piacquadio tells Dermatology Times.

According to the study data, one in 25 clinically diagnosed AK lesions that were identified by the investigators (board-certified dermatologists) were occult early stage squamous cell carcinomas on histological assessment.

The study was composed of 110 patients, with 220 clinically diagnosed untreated AKs at baseline, plus 51 AKs unresponsive to treatment.

In the study, six to 12 clinically diagnosed AK lesions on the face or scalp were randomized to receive either biopsy or ALA-PDT. Two of the lesions identified on enrollment were randomized to biopsy for each patient, and the remaining lesions were treated with ALA-PDT at baseline.

Quantifying frequency

Results showed that the clinical diagnosis and the histopathology matched in 91 percent of the lesions biopsied.

Of the biopsied lesions, 4 percent (11/271) showed benign changes and 5 percent (14/271) showed occult cutaneous malignancy (12 of which were squamous cell carcinoma and two of which were basal cell carcinoma).

"It may be that dermatologists know of the potential malignant transformation of AKs, but this study quantified the frequency of the actual occurrence, which again weighs in on the importance of effective and immediate treatment of these lesions," Dr. Piacquadio says.

The applicator sticks (Kerastick by Levulan; Dab-O-Matic by Dab-O-Matic Corp.) used in the study were designed to deliver 20 percent ALA HCL topical solution to the designated lesions. Retreatment of any remaining target lesion was done at month two, and biopsies of all nonresponding lesions were done at month three. All patients were treated with 10 J/cm2 visible blue light delivered at 10 mW/cm2 from a PDT illuminator. Patients in the study were followed up monthly for one year.

According to the data, more than 91 percent of the clinically diagnosed target lesions, including the baseline biopsy reference lesions and nonresponding lesions, were diagnosed as actinic keratoses.

The results point out that there was little difference between the incidence of all types of SCC at baseline and subsequent nonresponding lesions. This suggests that the treatment of ALA-PDT did not necessarily select out more severe lesions as one might have suspected. Furthermore, the study results also imply that ALA-PDT treatment does not have any cancer-promoting effects.