the latter case, patients who are at a particular stage of the lesions are mentioned, while in the former case there is no such specification. The Olsen grading was not used in the pivotal phase III studies for tirbanibulin32 and deviates from the primary global endpoint used in these studies which were: complete clearance (100%) of AK lesions (no prespecified classification of lesion grade). In addition, lesions of patients participating in phase III could be established as Olsen I or II, depending on the classification considered. In this regard, patient photographs taken at baseline in tirbanibulin phase III trials suggested that there could be patients with a mixture of Olsen grade I and II lesions within the same treatment area (up to 25 cm2).32
Situations such as this recent example should make us reconsider the endpoints used in clinical trials. These should preferably mirror those used in routine clinical practice, so the results of the research apply to this setting.
How to Deal with AK Daily Clinical Practice: Recommendations
Considering the abovementioned limitations and based on our clinical experience, we propose the following recommendations aiming to improve diagnosis, monitoring, and management of patients with AK.
Recommendation 1: To refocus clinical diagnosis, management, and monitoring endpoints toward an area-wide assessment rather than the assessment of individual AK lesions
Firstly, FC should be evaluated as a chronic disease with a high genetic mutational burden driven by radiation exposure from sunlight causing the development of future AKs or SCC. In clinical practice, dermatologists should assess the entire area affected by AK, rather than individual lesions, to optimize the treatment approach.1,24 Treatment of FC, in general, has been reported to help reduce the recurrence of AK lesions,12,33,34 and guidelines advocate field treatment,11,12,14 but without much further specification on how to define and classify FC status.
There should be an increasing and systematic shift towards field characterization of AK lesions as the importance of FC is becoming more evident in clinical practice. It would be useful to establish a consensus to define a universal grading system for UV skin damage. In this sense, there is also a lack of a universal optimal management score system to assess the overall efficacy of treatment. In most AK clinical trials, a efficacy is assessed by the achievement of complete clearance; although many patients only reach partial but substantial improvement.
Thus, we believe that partial clearance including reduction of AK burden (number of lesions) and improvement of UV skin damage parameters (FC), would represent more appropriate clinical endpoints.
Recommendation 2: To abandon the Olsen classification to guide AK management
We still consider that there is no objective method for clinical classification of AK lesions that correlates with a reliable histopathological classification. The Olsen classification appears to be poorly reproducible and inconsistent among experts for assessing severity and correctly guiding treatment.1 Moreover, this classification system is unreliable and inconsistent for routine application, with limited use in clinical practice.1,8,25 In our opinion, this classification is characterized by low feasibility and might provide a false understanding of the underlying lesions in terms of their risk of progression. Therefore, the inadequacy of Olsen's classification in both clinical trials and clinical practice implies that this classification should no longer be used as a guide for AK management.
Recommendation 3: To introduce into clinical routine a global assessment scoring system to characterize field cancerization
Unlike the Olsen grading system, the AKASI system tries to take a global view of the affected area, assessing aspects such as distribution and erythema. Thus, the approach to the diagnosis and monitoring of AK should consider the routine use of AKASI to assess UV-damaged skin. Also, this classification could be used to stratify the risk for developing iSCC, as AKASI grade has been associated with the incidence of iSCC.35 AKASI is simple and quick to perform, and therefore suitable for assessing disease severity in both clinical studies and daily practice.
Recommendation 4: To match efficacy endpoints between clinical trials and clinical practice
We recommend reviewing and standardizing, when possible, the endpoints for determining the clinical efficacy of treatment with respect to what is then assessed in routine clinical practice. Simultaneously, the use of treatments in daily practice should be contextualized with the type of endpoints assessed in clinical trials. This is observed in the study of psoriasis, another chronic skin disease (such as AKs and UV skin damage), where efficacy endpoints in clinical trials correspond to what is evaluated in clinical practice. That is, PASI is used both in daily routine36,37 and in clinical trials38,39 to measure disease severity, in order to adapt treatments accordingly.
Recommendation 5: To characterize actinic damage in actual practice
Actinic damage is not always specifically reported in medical records. We encourage to evaluate the following aspects to characterize actinic damage: pigmentation disorders, atrophy, telangiectasia, and sandpaper-like texture.
Situations such as this recent example should make us reconsider the endpoints used in clinical trials. These should preferably mirror those used in routine clinical practice, so the results of the research apply to this setting.
How to Deal with AK Daily Clinical Practice: Recommendations
Considering the abovementioned limitations and based on our clinical experience, we propose the following recommendations aiming to improve diagnosis, monitoring, and management of patients with AK.
Recommendation 1: To refocus clinical diagnosis, management, and monitoring endpoints toward an area-wide assessment rather than the assessment of individual AK lesions
Firstly, FC should be evaluated as a chronic disease with a high genetic mutational burden driven by radiation exposure from sunlight causing the development of future AKs or SCC. In clinical practice, dermatologists should assess the entire area affected by AK, rather than individual lesions, to optimize the treatment approach.1,24 Treatment of FC, in general, has been reported to help reduce the recurrence of AK lesions,12,33,34 and guidelines advocate field treatment,11,12,14 but without much further specification on how to define and classify FC status.
There should be an increasing and systematic shift towards field characterization of AK lesions as the importance of FC is becoming more evident in clinical practice. It would be useful to establish a consensus to define a universal grading system for UV skin damage. In this sense, there is also a lack of a universal optimal management score system to assess the overall efficacy of treatment. In most AK clinical trials, a efficacy is assessed by the achievement of complete clearance; although many patients only reach partial but substantial improvement.
Thus, we believe that partial clearance including reduction of AK burden (number of lesions) and improvement of UV skin damage parameters (FC), would represent more appropriate clinical endpoints.
Recommendation 2: To abandon the Olsen classification to guide AK management
We still consider that there is no objective method for clinical classification of AK lesions that correlates with a reliable histopathological classification. The Olsen classification appears to be poorly reproducible and inconsistent among experts for assessing severity and correctly guiding treatment.1 Moreover, this classification system is unreliable and inconsistent for routine application, with limited use in clinical practice.1,8,25 In our opinion, this classification is characterized by low feasibility and might provide a false understanding of the underlying lesions in terms of their risk of progression. Therefore, the inadequacy of Olsen's classification in both clinical trials and clinical practice implies that this classification should no longer be used as a guide for AK management.
Recommendation 3: To introduce into clinical routine a global assessment scoring system to characterize field cancerization
Unlike the Olsen grading system, the AKASI system tries to take a global view of the affected area, assessing aspects such as distribution and erythema. Thus, the approach to the diagnosis and monitoring of AK should consider the routine use of AKASI to assess UV-damaged skin. Also, this classification could be used to stratify the risk for developing iSCC, as AKASI grade has been associated with the incidence of iSCC.35 AKASI is simple and quick to perform, and therefore suitable for assessing disease severity in both clinical studies and daily practice.
Recommendation 4: To match efficacy endpoints between clinical trials and clinical practice
We recommend reviewing and standardizing, when possible, the endpoints for determining the clinical efficacy of treatment with respect to what is then assessed in routine clinical practice. Simultaneously, the use of treatments in daily practice should be contextualized with the type of endpoints assessed in clinical trials. This is observed in the study of psoriasis, another chronic skin disease (such as AKs and UV skin damage), where efficacy endpoints in clinical trials correspond to what is evaluated in clinical practice. That is, PASI is used both in daily routine36,37 and in clinical trials38,39 to measure disease severity, in order to adapt treatments accordingly.
Recommendation 5: To characterize actinic damage in actual practice
Actinic damage is not always specifically reported in medical records. We encourage to evaluate the following aspects to characterize actinic damage: pigmentation disorders, atrophy, telangiectasia, and sandpaper-like texture.
