12. Attachments – Actinic keratosis and squamous cell carcinoma of the skin

3.1

3.1

modified 2022

The data situation for prognostic factors of the transition AK -> SCC is not sufficient. At the moment, no reliable values for the probability of the transition AK -> SCC can be given.

The data situation for reliable prognostic factors of the transition from AK to SCC is not sufficient. At the moment, no reliable values for the probability of progression can be given. The following clinical factors are prognostically unfavorable:

·         Immunosuppression

·         Therapy resistance

·         Field cancerization

3.2

3.2

modified 2022

Because existing clinical and histological systems (e.g., classification according to Olsen or KIN 1-3) are not sufficiently prognostically validated, new classifications should be developed.

Existing clinical and histological systems (e.g., classification according to Olsen, grading in KIN 1-3, counting of lesions) are not sufficiently prognostically validated and thus dispensable in clinical practice.

4.2

new 2022

Scores integrating multiple qualitative and quantitative factors (e.g. AK-FAS, AKASI) improve the standardized assessment of actinic keratosis.

4.3

new 2022

Cheilitis actinica is etiologically and morphologically the counterpart of actinic keratosis of the keratinizing squamous epithelium of the skin at the labial red.

4.14

4.22

modified 2022

If SCC or Bowen's disease is clinically suspected, histology shall also be obtained to differentiate another benign or malignant neoplasm. Preoperatively, the maximum diameter of the neoplasm should be documented.

If squamous cell carcinoma of the skin, cheilitis actinica or Bowen's disease is clinically suspected, histology should also be obtained to differentiate another benign or malignant neoplasm.Preoperatively, the maximum diameter of the neoplasm should be documented for squamous cell carcinoma of the skin and Bowen's disease.

5.2

5.2

modified 2022

A combination of a field-directed with a lesion-directed therapeutic modality may be offered.

Primary or sequential combination therapy of different field- or lesion-directed modalities should be offered for actinic keratosis.

5.3

5.3

Modified 2022

Cryosurgery should be offered in a lesion-directed fashion for single or multiple Olsen grade I-III AK in immunocompetent individuals.

Cryosurgery should be offered for single or multiple actinic keratoses.

5.4

5.4

modified 2022

Surgical removal of grade I-III AK according to Olsen (e.g., by curettage, shallow ablation, or complete excision) should be offered for single lesions in immunocompetent and immunosuppressed patients.

Surgical excision (e.g., by curettage, shallow ablation, or complete excision) should be offered for single actinic keratoses.

5.5

5.5

modified 2022

Current data do not allow recommendations for therapy of AK with chemical peels.

Chemoexfoliation with peels may be offered for single or multiple actinic keratoses as well as for field cancers.

5.6

new 2022

Potassium hydroxide 5% solution may be offered for single or multiple actinic keratoses.

5.6

5.7

modified 2022

Treatment with ablative laser procedures may be offered for single or multiple Olsen's grade I-III AK and for field cancers in immunocompetent patients.

Ablative laser procedures may be offered for single or multiple actinic keratoses as well as for field cancerization.

5.7

5.8

modified 2022

Treatment with non-ablative laser procedures may be offered for single or multiple Olsen grade I-II AK.

Non-ablative laser procedures may be offered for single or multiple actinic keratoses.

5.8

5.9

modified 2022

Treatment with diclofenac sodium 3% in hyaluronic acid 2.5% gel should be offered for single or multiple grade I-II AK according to Olsen in immunocompetent individuals.

Diclofenac sodium 3% gel should be offered for single or multiple actinic keratoses.

5.9

5.10

Modified 2022

Field-directed therapy with diclofenac sodium 3% in hyaluronic acid 2.5% gel should be offered for field cancerization.

Diclofenac sodium 3% gel should be offered for field cancerization.

5.10

5.11

modified 2022

5-Fluorouracil 5% cream should be offered for the treatment of single and multiple Olsen grade I-II AK.

5-Fluorouracil 5% cream should be offered for single and multiple actinic keratoses.

5.11

5.12

modified 2022

Field-directed therapy with 5-fluorouracil 5% cream should be offered for field carcinomatization.

5-Fluorouracil 5% cream should be offered for field cancerization.

5.13

new 2022

5-Fluorouracil 4% cream should be offered for single and multiple actinic keratoses and in field cancerization.

5.12

5.14

modified 2022

Evidence is available for the efficacy of 5-fluorouracil 0.5% cream for single and multiple grade I-II AK according to Olsen. However, there is currently no approval for this concentration in Germany.

There is evidence for the efficacy of 5-fluorouracil 0.5% cream in single and multiple actinic keratoses. However, there is currently no approval for this concentration in Germany.

5.13

5.15

modified 2022

5-Fluorouracil 0.5% with salicylic acid 10% in solution should be offered lesion-directed or field-directed for single or multiple grade I-II AK according to Olsen and for field carcinomatization in immunocompetent individuals.

5-Fluorouracil 0.5% with salicylic acid 10% in solution should be offered for single or multiple actinic keratoses as well as for field cancerization.

5.14

5.16

modified 2022

Ingenol mebutate should be offered as field-directed therapy for single or multiple grade I-II Olsen's AK and for field carcinomatization.  suspended as a result of dormant approval (see Red Hand Letter).

Ingenol mebutate should not be offered for actinic keratosis therapy.

5.15

5.17

modified 2022

Imiquimod 5% cream should be offered on a field-directed basis for single or multiple grade I-II AK according to Olsen and for field cancerization in immunocompetent individuals.

Imiquimod 5% cream should be offered for single or multiple actinic keratoses as well as for field cancerization.

5.17

5.18

modified 2022

Imiquimod 3.75% cream should be offered field-directed for multiple grade I-II AK according to Olsen and for field cankerization in immunocompetent individuals on the face or hairless capillitium.

Imiquimod 3.75% cream should be offered for multiple actinic keratoses as well as in field cancerization.

5.19

new 2022

Tirbanibulin 1% ointment should be offered for single or multiple actinic keratoses as well as for field cankerization.

5.18

5.20

modified 2022

Conventional photodynamic therapy with 5-aminolevulinic acid or its methyl ester (5-ALA or MAL) should be offered on a field-directed basis for single or multiple grade I-II AK according to Olsen and for field cancers.

Red light photodynamic therapy with 5-aminolevulinic acid (ALA) or its methyl ester (MAL) should be offered for single or multiple actinic keratoses and in field cancerization.

5.19

5.21

modified 2022

MAL in combination with daylight (daylight MAL-PDT) should be offered on a field-directed basis for nonpigmented, single or multiple grade I-II AK according to Olsen, and for field cancers on the face and capillitium in immunocompetent individuals.

Photodynamic therapy with natural or simulated daylight with 5-aminolevulinic acid (ALA) or its methyl ester (MAL) should be offered for single or multiple actinic keratoses as well as for field cancerization.

5.23

5.22

modified 2022

Treatment with photodynamic therapy with MAL in combination with illumination by an artificial red light source (630 nm) should be offered for single or multiple grade I-II AK according to Olsen, as well as for field cancerization in immunosuppressed patients.

Photodynamic therapy with red light using 5-aminolevulinic acid (ALA) or its methyl ester (MAL) should be offered for single or multiple actinic keratoses as well as in field cancerization in immunosuppressed individuals.

5.24

5.23

Modified 2022

Field-directed therapy with imiquimod 5% cream may be offered to immunosuppressed patients with multiple grade I-II AK according to Olsen, as well as in field cancerization. In this case, the lack of approval should be noted.

Imiquimod 5% cream can be offered for single or multiple actinic keratoses as well as for field cancerization in immunosuppressed individuals. In this case, the lack of approval should be noted.

5.25

5.24

modified 2022

Therapy with diclofenac sodium 3% in hyaluronic acid 2.5% gel should be offered to patients with single or multiple grade I-II AK according to Olsen as well as in field carcinomatization under immunosuppression.

Diclofenac sodium 3% gel should be offered for single or multiple actinic keratoses as well as for field cancerization in immunosuppressed individuals.

6.1

new 2022

The indication for therapy of Cheilitis actinica should be made in synopsis of the clinical picture, risk factors (e.g., immunosuppression, cumulative UV exposure, infestation of the entire lower lip, infestation also of the upper lip), comorbidities, life expectancy, and patient wishes.

6.2

new 2022

Before choosing a treatment procedure, a biopsy should be performed for diagnostic confirmation and to exclude invasive squamous cell carcinoma.

6.3

new 2022

Histological control should be performed if there is clinical evidence of a lack of response or incomplete response to therapy.

6.4

new 2022

Surgical removal of cheilitis actinica (e.g., by vermilionectomy or lip-shave with histologic workup and information on the status of resection) should be offered in cases of extensive involvement.

6.5

new 2022

Treatment of cheilitis actinica with ablative laser procedures (_CO2, Er:YAG) may be offered.

6.6

new 2022

The insufficient data situation does not allow recommendations for the therapy of cheilitis actinica with non-ablative laser procedures.

6.7

new 2022

The data situation on cryosurgery does not allow a conclusive assessment of the therapy of cheilitis actinica. 

6.8

new 2022

Chemical peeling should not be used in the therapy of cheilitis actinica due to a lack of evidence of benefit.

6.9

new 2022

Treatment with diclofenac sodium 3% gel may be offered for cheilitis actinica.

6.10

new 2022

Insufficient data do not allow an evidence-based recommendation for topical therapy of cheilitis actinica with 5-fluorouracil.

6.12

new 2022

Photodynamic therapy with red light and 5-aminolevulinic acid (ALA) or its methyl ester (MAL) should be offered for the treatment of cheilitis actinica.

6.13

new 2022

Methyl aminolevulinate (MAL) in combination with natural or simulated daylight (MAL-dlPDT) should be offered for therapy of cheilitis actinica.

7.1

new 2022

Prior to therapy for Bowen's disease, a biopsy should be performed to exclude invasive squamous cell carcinoma, other neoplasia, or inflammatory dermatosis. (Reference to chapter Diagnostics Recommendation 4.15.).

Histological control should be performed if there is clinical evidence of a lack of response or incomplete response to therapy.

7.2

new 2022

Surgical excision of Bowen's disease (e.g., by shallow ablation or complete excision) should be offered for individual lesions.

7.3

new 2022

Cryosurgery may be offered for the treatment of Bowen's disease.

7.4

new 2022

Ablative laser procedures may be offered for the treatment of Bowen's disease.

7.5

new 2022

5-Fluorouracil 5% cream should be offered for the treatment of Bowen's disease.

7.6

new 2022

Imiquimod 5% cream may be offered for the treatment of Bowen's disease in immunocompetent individuals. In this case, the lack of approval should be noted.

7.7

new 2022

Photodynamic therapy with red light should be offered for the treatment of Bowen's disease in 2 therapy cycles within 4 weeks. 

7.8

new 2022

Pretherapy (e.g., ablative fractional laser procedures, microneedling) may be offered prior to performing photodynamic therapy with red light for penetration enhancement.

8.1

new 2022

The examining pathologist/dermatopathologist should be informed of the following risk factors of SCC if present: recurrence, tumor diameter >2 cm, localization ear, lip or temple, immunosuppression and evidence of perineural invasion, no displaceability from the subsurface.

8.2

new 2022

Surgical therapy of the primary tumor should be performed according to the following algorithm: see here.

6.9

8.12

modified 2022

Adjuvant radiotherapy should be performed if risk factors are present:  Scarce resection margin (<2 mm, in the absence of the possibility of resection) Extensive perineural sheath infiltration.

Adjuvant radiotherapy should be performed in the presence of extensive perineural sheath infiltration.

6.9

8.13

modified 2022

Adjuvant radiotherapy should be performed in the presence of risk factors:  Scarce resection margin (<2 mm, in the absence of the possibility of resection) Extensive perineural sheath infiltration.

Adjuvant radiotherapy may be considered if the resection margin is narrow.

8.14

new 2022

Current data do not support a recommendation for combining adjuvant radiotherapy with systems therapy.

8.20

new 2022

In the case of (distant) metastasis or locally advanced disease that cannot be controlled by surgical or radiotherapeutic intervention or can be controlled only with major limitations in functionality, the indication for system therapy should be considered.

8.21

new 2022

The indication for systems therapy should be made in an interdisciplinary tumor board.

8.22

new 2022

Patients with locally advanced or metastatic SCC should be offered first-line immunotherapy with a PD‐1‐inhibitor approved for this indication.

8.23

new 2022

In case of progression under PD‐1‐blockade or contraindications to this type of immunotherapy, EGFR‐directed therapy or chemotherapy should be offered.

7.1

9.1

Modified 2022

Follow-up of patients with cutaneous SCC* should be offered at risk-adjusted intervals according to the following schedule:

Follow-up of patients with squamous cell carcinoma of the skin should be offered at risk-adapted intervals according to the following schedule:

9.2

new 2022

The following examination methods are recommended depending on risk factors of the primary tumor, immunosuppression or after locally advanced and metastatic squamous cell carcinoma of the skin according to the present scheme:

7.3

9.4

modified 2022

Lymph node ultrasonography should be performed in patients at increased risk of metastasis or with unclear palpation findings.

Lymph node ultrasonography should be performed in patients at high risk of metastasis* or with unclear palpation findings and in cases of Z.n. locally advanced and metastatic squamous cell carcinoma of the skin.

*High risk: TD >6mm, >4mm in desmoplasia, G3-4 differentiation, perineural tumor growth, immunosuppressed and patients with secondary tumors.

7.4

9.5

modified 2022

X-ray thoracic examinations should not be routinely performed in follow-up. Abdominal ultrasonography should not be routinely performed in follow-up.

X-ray thoracic examinations and abdominal sonography should not be routinely performed in follow-up.

7.5

9.6

modified 2022

Cross-sectional imaging should be performed to clarify recurrences, e.g., with suspected involvement of functional structures or when perineural tumor growth or metastasis-supecific findings are suspected.

Cross-sectional imaging should be performed to clarify recurrences, e.g., with suspected involvement of functional structures, in cases of locally advanced or metastatic squamous cell carcinoma of the skin, or with suspected perineural tumor growth or metastasis-supecific findings.

9.7

new 2022

All patients with squamous cell carcinoma of the skin (e.g., even with a tumor thickness of ≤2.0 mm without the presence of other risk factors) should be followed up due to the possible development of secondary skin tumors. The frequency of follow-up should also take into account the number of actinic keratoses as well as squamous cell carcinomas of the skin in the history.