Nashville, Tenn. — The difficulty of treating multiple actinic keratoses (AKs) and squamous cell carcinomas (SCCs) on the legs demands that dermatologists consider multiple modalities and monitor patients closely for invasive SCC, an expert says.

Though multiple AKs and SCCs occur most commonly on the head and neck, "They also occur on the lower extremities," says Michel A. McDonald, M.D., M.B.A., director of cosmetic dermatology surgery and Mohs micrographic surgery at Vanderbilt University, Nashville, Tenn.

It's also common for females to have more than 25 lesions per extremity, she says.

Such patients often possess histories of prolonged tanning up to 20 years before their AKs or SCCs began developing, Dr. McDonald explains. Radiation exposure represents another common denominator. She reveals that one patient she has treated played extensively with an x-ray machine as a child.

In treating multiple lower-extremity AKs and SCCs, Dr. McDonald says that because definitive answers remain elusive, "I try everything — cryosurgery, field treatment with topical agents, photodynamic therapy (PDT), potentially laser therapy for more involved cases, then biopsy and electrodessication and curettage (EDC) times three."

Cryotherapy can be effective for smaller numbers of AKs, she says. "In a large retrospective review of 1,000 AKs treated with this therapy, 98 percent remained cured at one year (Lubritz RR; Smolewski SA. J Am Acad Dermatol. 1982 Nov;7(5):631-2.)"

A similar German study showed recurrence rates of 2.1 percent at one year and up to 11.5 percent at three years (Zouboulis CC, Röhrs H. Hautarzt. 2005 Apr;56(4):353-8. Review.)

However, Dr. McDonald notes, "The problem with cryosurgery is that it doesn't allow for field treatment. And when the patient has 20 or 30 lesions on the lower extremities, it's hard to utilize cryosurgery alone."

Imiquimod and five-fluorouracil (5-FU) facilitate field treatment, as well as greater patient control of therapy, she says. Although various studies support different treatment regimens, Dr. McDonald says, "I tend to prescribe imiquimod three days a week for 16 weeks. But I'll often do cyclic therapy — four weeks on, four weeks off. We're often doing courses of this multiple times during the year," treating different areas of the legs rather than the whole leg at once.

Imiquimod is not approved for SCC in situ, but studies show 93 percent clinical clearance with daily use, she says. However, she adds, "I don't believe my patients would tolerate this very well."

With 5-FU, "I tend to prescribe 5 percent cream twice a day for two to four weeks." Because patients can experience intense responses to this drug, "I've had to discontinue it on the legs as field treatment, and I rarely use it as field treatment over the entire leg at once.", Dr. McDonald says.

In case reports involving three patients with diffuse AKs and SCCs, applying five percent 5-FU under Unna wraps for four to 20 weeks cleared many of the AKs before investigators performed surgery on the invasive SCCs (Mann M, Berk DR, Peterson J. J Drugs Dermatol. 2008 Jul;7(7):685-8. )

"Patients also experienced a reduction in clinical lesions for up to three years." Such a treatment puts more control into the physician's hands if patients are noncompliant, she says.

Photodynamic therapy (PDT) has achieved clinical clearance rates between 68 percent and 75 percent for AKs located on the head and neck, Dr. McDonald says. "But 71 percent of patients with clinical clearance on the head and neck have only partial response in the lower extremities."

Similarly, she says that in experience, "I do not find the same response on the lower extremities as I do on the head and neck."

Accordingly, she states, "Patient selection is very important. Hyperkeratotic AKs do not respond as well."

She suggests pretreating these AKs with curettage, imiquimod or 5-FU before applying PDT.

"Sometimes I'll also treat patients after PDT with imiquimod. Often, PDT is not the only thing I'm doing."

Dr. McDonald says that in other body locations, she incubates the aminolevulinic acid photosensitizer for one hour.

"That works fairly well for me on the head and neck. But since I wasn't getting the same response in the lower extremities, I've increased incubation to three hours and started occluding some patients."

The biggest challenge with such treatments is having patients spend a full day in the office, she says. "We use the blue light (417 nm), initially for 16 minutes, then increase as tolerated."

For more difficult cases, including hyperkeratotic AKs, Dr. McDonald says, "Laser resurfacing is something to consider."

Initially, she says she used a CO2 laser (UltraPulse, Lumenis) for this purpose, though more recently she has switched to other lasers for treating the lower extremities.

In one case, "The patient didn't like the hypopigmentation that occurred after cryosurgery." As an alternative, Dr. McDonald says she tried a Q-switched Nd:YAG (532 nm) laser, followed by phototherapy, which proved effective and satisfied the patient.

However, Dr. McDonald says that whatever modality one uses, "I worry in these patients — am I treating AK or SCC? In many of these patients, we're probably treating at least SCC in situ, not just AK."

To help ensure that she isn't missing invasive SCC, she performs periodic biopsies in patients undergoing multiple courses of treatment. Rather than excision, Dr. McDonald says she often uses EDC times three for invasive SCC.

"This is the one patient population where I biopsy EDC times three on the same day. Because I'm biopsying 16 to 18 suspected SCCs on the same day, I'm not going to bring them back and do that later."

Dr. McDonald says she also prefers Mohs surgery for locations including the pre-tibial region, foot or digit because these areas carry a higher risk of metastasis and are difficult to close.

"The criteria that influence me toward doing Mohs surgery are the same criteria we use in the head and neck — tumor site, large tumor size, tumor differentiation and the presence of spindle cells, desmoplasia or perineural invasion."

Furthermore, she recommends biopsy for anything that appears suspicious. "Because these patients can have a whole field of SCC in situ, you can be fooled and end up with a more aggressive tumor than you suspected clinically."DT

Disclosure: Dr. McDonald reports no relevant financial interests.