Actinic Keratoses: Evaluating Management Strategies

W hen treating actinic keratoses (AKs), do you discuss multiple treatment options? Do you know what factors are most important to patients when choosing a therapy? How about your perspective: What’s most important to you when prescribing treatment? To answer these questions and more, we asked a mix of patients and physicians their thoughts. A few facts about AKs As our patients age, we’re likely to treat an increasing number of patients with AKs. Already: • approximately 1 in 6 Americans during their lifetimes will develop AK.1 • about 60% of predisposed patients in the United States older than 40 are afflicted with at least one AK.2 • more than 1 million new cases of AK are reported annually, representing one-fourth of the total patient visits for AK each year.3 • without treatment, all AK lesions have the potential to progress to invasive squamous cell carcinoma (SCC). Traditional therapies for AK include cryotherapy and topical 5-fluorouracil (5-FU). More recently, photodynamic therapy (PDT), utilizing aminolevulinic acid (ALA) 20% topical solution combined with blue light photoactivation, has proved an effective therapy in controlled clinical trials. ALA/PDT, the only photodynamic therapy treatment available in the United States for dermatology, was approved by the FDA in September 2000. Are Patients Satisfied? But are our patients satisfied with the choice and level of treatments they’re receiving? Are we as dermatologists satisfied with the treatments available? Recently, 104 patients (52 male, 52 female) and 68 U.S.-based dermatologists (60 male, 8 female) were surveyed about their perceptions of AK treatments. Given the constant evolution of AK lesions, long-term monitoring is recommended and subsequent treatment is often required. Therefore, patient and physician perceptions of various factors related to treatment benefits and limitations are relevant to the long-term success of AK management. Additionally, restrictions imposed by managed care plans have significantly affected access to care, as well as treatment choice and satisfaction for both patients and physicians. In a different telephone survey of dermatologists, numerous concerns were expressed regarding cryotherapy, topical 5-FU, and curettage (see “Physician Attitudes,” page 50), emphasizing unmet needs for AK treatments.4 Read on to find out results of the survey of patients and dermatologists regarding their perspectives of available medical therapies currently approved by the FDA (i.e. topical 5-FU) and conventional surgical approaches (i.e. cryotherapy, curettage). At the time of survey completion, it was too early to assess perceptions of ALA/PDT and topical diclofenac 3% gel as it was not yet available in the United States. Continuum of Malignancy Previously defined as “premalignant,” AKs are best perceived as the early stage in the continuum of squamous cell malignancy. This concept is supported by clinical observation, histologic study and genetic analysis. During several years of individual patient management, dermatologists have observed potential for progression of AK to SCC.3,5 Based on data collected from multiple clinical studies, the risk of AK progression to invasive SCC has been estimated to range from 0.025% to 16%.3 Development of SCC in one or more AK lesions has been reported to occur in up to 20% of patients, with the overall lifetime risk of progression of AK to SCC estimated to be 6% to 10%.6,7 Histologic association of AK and SCC is a common observation, seen routinely on evaluation of biopsy or surgery specimens.8,9 The association between AK and SCC also is supported by genetic analysis. Investigation of the tumor suppressor gene p53, which encodes proteins involved in repair of DNA altered by ultraviolet exposure, identified mutations in 69% of SCC and 53% of AK analyzed.10 Nonmelanoma skin cancer, primarily composed of basal cell carcinoma (BCC) and SCC, is extremely common, representing 96% of all new skin cancers.11 The incidence of SCC has increased 4% to 8% during the past 3 decades.12 Although SCC comprises only 25% to 30% of nonmelanoma skin cancer, SCC accounts for 75% of skin cancer-related mortalities.13 Approximately 1,900 deaths are attributed each year to nonmelanoma skin cancers. BCC may cause extensive local tissue destruction, which can result in significant morbidity. The incidence of perineural invasion with SCC (2.4% to 4.9%) is much greater than with BCC (0.92%).14 Mucosal SCC of the lip is associated with significant metastatic potential (6.7% to 12%).13,14 The mortality rate associated with SCC ranges from 1% to 22% depending on disease stage, with 18.6% noted in unselected cases with regional metastasis.13,14 Recent studies report lower mortality rates, likely reflecting more aggressive and effective therapy for both SCC and AK.13 Treating AKs is logical from both a scientific and a clinical perspective. SCCs involve the head and neck region, including critical anatomic locations such as the ears, lips, nose and periocular region. Clearing AK lesions interrupts their progression to SCC, and effective AK therapy prevents potential sequelae of SCC, such as local tissue destruction, metastasis and possible fatality.15 Some healthcare initiatives have attempted to diminish the significance of AK as a disease state. Observations that some AKs may spontaneously involute have contributed to the argument to downplay the need for AK therapy or regulate its administration. It is well recognized that many AKs don’t spontaneously resolve, and at present it’s not possible to predict which AKs will progress to invasive SCC and which may regress without therapy.15 From a therapeutic perspective, treatment of AKs is fully warranted. Available Treatment Modalities Currently, we have many therapeutic modalities available for treating AK, including liquid nitrogen cryotherapy, topical 5-FU, curettage, dermabrasion, and peeling procedures.16 Cryotherapy is the most common treatment method for AK in the United States, whereas topical 5-FU is used in about 3.6% of visits for AK.16 ALA/PDT has demonstrated positive efficacy and safety, although its recent introduction in the United States (September 2000) makes it too soon to quantify its relative frequency of use. But, in controlled clinical trials of ALA/PDT, 94% of patients rated cosmetic response as ‘excellent’ or ‘good,’ and 84% of patients said they would use ALA/PDT again for recurring AKs.17 Distinct advantages and disadvantages are associated with each of the treatment modalities for AK. Cryotherapy, although convenient and quick, is associated with pain, blistering and risk of permanent hypopigmentation. Protracted healing may occur as the tissue reaction resolves. Unlike cryotherapy, topical 5-FU allows for diffuse treatment of subclinical AK lesions but is associated with predictable erythema, inflammation, severe irritation and discomfort throughout the treatment period as well as several days afterward. Curettage is a simple treatment method usually limited to hyperkeratotic AK lesions. This method is associated with possible scarring and textural skin changes. Who Was Surveyed The results of the survey represent the viewpoints of 104 patients who underwent treatments carried out over several years by one or more physicians. The doctors were located in the southwest region of the United States, primarily in Nevada and southern California. “Questions Asked of Patients” on page 53 highlights question categories used for patients in this survey. Patients ranged in age from 25 years to 84 years; 57.6% of patients were at least age 55. Most presented with a duration of AK diagnosis of 6 to 10 years or more and reported treatment of 11 to 15 AK lesions per session, mostly with lesions on the face, head and neck. The 68 U.S. dermatologists surveyed encompassed practitioners from more than 10 states. “Questions Asked of Physicians” on page 53 illustrates question categories used for dermatologists in this survey. Of the dermatologists surveyed, 88% were more than 35 years of age and in private, solo or group practice; 80% of those doctors had been in practice at least 10 years. Patient Survey Results With that said, let’s take a look at the results. First, cryotherapy was the treatment modality used by the majority of patients (83%), whereas 14% of patients reported undergoing treatment with topical 5-FU. The remainder were treated with various peeling modalities. None of the patients in this survey reported being treated with curettage or ALA/PDT. In terms of convenience, 71% of patients surveyed preferred cryotherapy; 67% perceived this modality to be “very effective.” All cryotherapy patients acknowledged side effects such as swelling and pain, though most deemed them tolerable. Half the patients treated with topical 5-FU reported complete or partial satisfaction with efficacy and cosmetic outcome. Response was mixed with respect to convenience and tolerability. Some patients voluntarily expressed an unwillingness to repeat topical 5-FU therapy because of adverse effects, prolonged skin irritation and healing times. The same percentage of patients (89%) surveyed indicated that they neither inquired about any specific form of treatment for AK nor were they offered a choice of treatments. They reported that their dermatologist suggested a specific treatment modality. Regarding perception of treatment selection, patients found: • efficacy as the most significant factor • convenience of treatment was a factor that drew divided responses. Many respondents rated this factor as either “significant” or “not/least important” • side effects (for example, discomfort, redness, swelling, blistering) and cosmetic outcome were rated “very important” or “somewhat important” by 55% and 66% of patients, respectively. • Cost was not considered a major factor by most patients — most patients acknowledged having adequate insurance coverage. A notable exception was limited or lack of prescription coverage for some patients treated with topical 5-FU. When asked if they’d have an interest in trying other AK options that they hadn’t tried yet, 75% of the respondents said they were interested. All of the patients treated with topical 5-FU expressed interest in pursuing other forms of therapy. Dermatologist Survey Results Of the physicians surveyed, 91% reported treating >20 patients weekly for AK, and 58% reported treating >50 patients weekly for AK. With regard to choice of terminology in describing AK to their patients, 62% of the doctors described AK as a “precancer,” 41% chose to teach patients the specific diagnostic term “actinic keratosis,” and 1% of dermatologists described AK to their patients as “sun spots.” Of those surveyed, 86% chose cryotherapy as the most common treatment, and only 13% chose topical 5-FU. Five dermatologists indicated they’ve started to gain experience with ALA/PDT. As for factors influencing the dermatologists’ treatment selection: • 100% indicated that efficacy is more important • 85% rated patient satisfaction as “very important” or “somewhat important” • 65% said side effects such as pain and discomfort are “somewhat important,” while 15% didn’t rate side effects as an important parameter for treatment selection • 50% rated cosmetic outcome as “very important, 18% rated it as “somewhat important,” and 32% rated it as “not important” • 53% rated quicker healing as “somewhat important.” Dermatologists also were surveyed about their perception of patients’ levels of satisfaction with individual treatment modalities. Almost half perceived their patients as not fully satisfied with cryotherapy. For treatment of AK with topical 5-FU, 89% reported that their patients were not fully satisfied. Twenty-nine percent indicated they don’t currently prescribe or only rarely recommend topical 5-FU therapy, while 62% reported they don’t utilize curettage to treat AK. The five dermatologists who indicated some experience with ALA/PDT noted initial favorable impressions regarding its efficacy and patient satisfaction. Eighty-five percent indicated a high level of interest in additional treatment options for AK beyond the modalities they currently utilize or are familiar with, based on previous clinical experience. Other Important Observations The majority of patients participating in this survey weren’t offered a selection of treatment options. This observation appears consistent with findings from discussion group surveys of 93 patients with AK from the United States, Germany, Spain and Australia.11 In those surveys, all patients reported getting little or no information about treatment options for AK, relying on physician judgment for therapy choice. All patients expressed a desire for more information about treatment s, including choices that may be associated with lower risk of pain, dyspigmentation and scarring. Some patients expressed a poor understanding of possible side effects before undergoing therapy, and some indicated willingness to sacrifice a limited degree of efficacy to experience fewer adverse sequelae. In the telephone study of physicians cited previously, 100 board-certified dermatologists rated the need for newer treatment modalities as 6.3 on a 10-point scale.4 In the survey described here, a high percentage of both patients and physicians indicated a strong level of interest in new treatment options for AK beyond the conventional methods. This fact, coupled with the limitations expressed by physicians experienced in both cryotherapy and 5-FU, strongly supports a need for new treatment modalities such as ALA/PDT. Moreover, patient ranking of efficacy, side effects, and cosmetic outcome as the most important factors in choosing an AK treatment further accentuate the therapeutic value of newer treatment modalities. The Bottom Line AK is a common early manifestation of SCC, warranting treatment to reduce the risk of progression to invasive disease. Results of the survey reported here indicate that both physicians and patients are only partially satisfied with conventional AK therapies. Many patients treated for AK don’t receive adequate information regarding available treatment options, and they want to participate in making informed choices and decisions regarding therapy. Perceived limitations of conventional AK therapies by patients and physicians alike underscore the need for new therapies that exhibit high efficacy and few undesirable short- and long-term adverse effects. Controlled clinical trials and patient satisfaction evaluations, such as those completed with ALA/PDT are needed with other modalities to verify their efficacy, safety and impact on quality of life. This will enable better established actual cure rates with therapies beyond what’s currently perceived, based on limited study data and clinical experience.