The goal of treatment for severely sun-damaged patients’ lesions is field therapy, which not only treats what dermatologists see, but also subclinical disease.
Treating severely sun-damaged patients’ individual lesions with cryotherapy alone is unlikely to lead to optimal outcomes. That’s because of a concept called field cancerization, which suggests that cancer does not arise as an isolated cellular phenomenon, but rather as an anaplastic tendency involving many cells simultaneously, according to Anokhi Jambusaria, M.D., M.S.C.E., staff dermatologist, Baylor Scott and White Health, Round Rock, Texas.
Dr. Jambusaria“In other words, some skin cancers are not happening as an isolated occurrence, but in a background of severely sun-damaged skin,” according to Dr. Jambusaria, who presented on the topic of extreme dermatoheliosis in July at the American Academy of Dermatology’s (AAD’s) Summer Meeting in Boston, Mass.
“The presence of field cancerization represents a high-risk population with subclinical invisible disease, multiple primary tumors and premalignant change. Oftentimes, they need multiple and repeated treatments, leading to significant morbidity. Treatment of patients with field cancerization, therefore, should involve targeting the entire area, not just the individual tumor.”
The main thing for dermatologists treating these patients to remember is that the goal of treatment is some type of field therapy, which not only treats what dermatologists see, but also subclinical disease. They should consider - even in the case of field disease - whether or not their treatment is penetrating deeply enough to treat the pathology, she says.
“Some patients develop such thick hyperkeratotic scale that application of topical 5 fluorouracil creams may not be getting to the targeted cell,” Dr. Jambusaria says.
Recently published reports suggest specific multimodal treatments effectively address field cancerization.
In a case series1 by Jambusaria-Pahlajani, et al, researchers described four transplant patients with field cancerization, who had failed topical chemotherapy and cryotherapy. The patients were treated with curettage of hyperkeratotic lesions, followed by topical 5 fluorouracil twice daily, followed by photodynamic therapy (PDT) with one hour incubation.
“All patients had excellent response rates, with total or near total clearing of their disease. This treatment was tolerated well by most patients and had a durable response [rate] of up to 18 months,” Dr. Jambusaria says.
In another study of 12 patients2 with numerous squamous cell carcinomas, cyclic photodynamic therapy administered every four to eight weeks for two years reduced SCC development by 95%, according to Dr. Jambusaria.
Chemowraps with 5 fluorouracil might also be a good treatment option for some patients, according to the dermatologist.
“Based on anecdotal experience, topical 5 fluorouracil applied to the legs yields less inflammation/irritation then when applied to the face,” she says. “These areas are also likely to have full thickness atypia in the form of SCCis and superficial invasive disease.”
Given these scenarios, dermatologists should consider using chemowraps with 5 fluorouracil. Hyperkeratotic lesions may be treated with curettage before applying the first chemowrap, according to Dr. Jambusaria.
“A liberal amount of 5 fluorouracil is applied to the area followed by [an] Unna boot. Application is typically on a Monday and the Unna boot is left on for five to seven days before removing. Patients are able to remove the Unna boot at home. If the plan is to keep the Unna boot on for the full seven days, patients are asked to remove the Unna boot the night before reapplication,” Dr. Jambusaria says.
“In my experience, I will leave the first Unna boot on for five days, and then have the patient come back to re-assess, given one case report where the patient developed exuberant ulceration from chemowraps leading to systemic 5 fluorouracil toxicity from absorption. If [the patient does] not have a significant reaction for the first two weeks, then I will have the patient leave [it] on for a full week, removing the Unna boot at home the night prior to coming back in,” she says.
Typically, these patients need three to four weeks of treatment to achieve moderate inflammation and minor superficial ulceration, which Dr. Jambusaria says is her treatment endpoint.
NEXT: Common scenarios
Dr. Jambusaria offers a few scenarios that dermatologists might typically encounter in practice.
Scenario #1: A patient with diffuse actinic keratosis/field cancerization on the face, many of which are hyperkeratotic, who failed treatment with topical 5 fluorouracil.
Treatment options include multimodality treatment with curettage of hyperkeratotic actinic keratosis, followed by five days of 5 fluorouracil twice daily, followed by photodynamic therapy with 1 hour incubation. The patient most likely failed treatment because of hyperkeratotic lesions, which made it impossible for the medication to penetrate below the scaling, she says. Another potential problem is many patients do not adhere to topical 5 fluorouracil treatment because of the therapy’s side effect profile, Dr. Jambusaria says.
“This multimodality treatment allows to direct aggressive treatment to the most hyperkeratotic areas by curettage and limits the length of therapy and time that the skin will be red/inflamed by priming the skin with topical 5 fluorouracil before photodynamic therapy,” she says. “Most patients are red/inflamed for 14 days total, with the worst being three days after PDT. This is in stark contrast to the anticipated three to four weeks quoted by most dermatologists who prescribe topical 5 fluorouracil (assuming a two-week use followed by [a] one-to-two week recovery period).”
Scenario #2: Patient develops five to 10 SCCs in one area in the past 12 months.
Treatment options include cyclic photodynamic therapy. In this treatment, patients get blue light photodynamic therapy with one hour incubation every four to eight weeks, for an extended period of time, according to Dr. Jambusaria.
“In a clinical trial of high-risk patients, cyclic PDT caused a 95 percent reduction in squamous cell carcinomas at the 2 year mark,” she says.
Another option is the use of oral retinoids. Based on anecdotal experience, patients who develop more than five SCCs in a 12-year period are good candidates to go on Soriatane (acitretin, Stiefel). In a study of 38 patients3 with multiple SCCs, half who were treated with Soriatane and half with placebo, Two of the 19 (or 11 percent) in the treatment group versus nine of 19 (47 percent) in the placebo group developed SCC during the study period.
Soriatane must be taken long term because if it is stopped, the rate of SCC development increases to what it was before the drug was started, according to Dr. Jambusaria.
Patients must be counseled on Soriatane risks and their lab work closely monitored, she says.
NEXT: Derms know best
Dermatologists understand cutaneous oncology better than any other physician, according to Dr. Jambusaria.
“We have the unique ability to look at a lesion, and … tell with reasonable accuracy if there is partial epidermal dysplasia (actinic keratosis), full thickness epidermal dysplasia (SCCis), or invasion into the dermis (invasive SCC). For this reason, we are able to correctly choose the appropriate therapies for patients and know when a biopsy is warranted or when empiric therapy can be done,” she says. “These patients can be time consuming, but with aggressive therapy, frequent visits and close monitoring, one can significantly decrease field cancerization, ultimately leading to development of fewer skin cancers and decreased morbidity for the patient.”
Disclosure: Dr. Jabmbusaria reports no relevant disclosures.
1 Jambusaria-pahlajani A, Ortman S, Schmults CD, Liang C. Sequential Curettage, 5-Fluorouracil, and Photodynamic Therapy for Field Cancerization of the Scalp and Face in Solid Organ Transplant Recipients. Dermatol Surg. 2016;42 Suppl 1:S66-72.
2 Willey A, Mehta S, Lee PK. Reduction in the incidence of squamous cell carcinoma in solid organ transplant recipients treated with cyclic photodynamic
therapy. Dermatol Surg. 2010 May;36(5):652-8. doi: 10.1111/j.1524-4725.2009.01384.x. Epub 2009 Nov 4
3 Bavinck JN, Tieben LM, Van der Woude FJ, Tegzess AM, Hermans J, ter Schegget J, Vermeer BJ. Prevention of skin cancer and reduction of keratotic skin lesions
during acitretin therapy in renal transplant recipients: a double-blind, placebo-controlled study. J Clin Oncol. 1995 Aug;13(8):1933-8.