Aetna actinic keratoses coverage update

Medically Necessary Interventions

Aetna considers the following procedures medically necessary for treatment of actinic keratoses:

Primary lesion-directed or topical therapies: Destruction of actinic keratoses lesions using either cryosurgery with liquid nitrogen OR topical diclofenac, imiquimod, ingenol mebutate gel, or 5-fluorouracil (with or without tretinoin)

Surgical removal when SCC suspected: Curettage or excision when squamous cell carcinoma is suspected AND submission of a specimen for histologic analysis is needed

Specimen submission required as part of procedure

Second-line destructive therapies: Destruction of actinic keratoses using chemical peel, dermabrasion, laser therapy, or photodynamic therapy for members who have failed to adequately respond to topical imiquimod or 5-FU, or to cryosurgeryfailure of topical imiquimod or 5-FU, or cryosurgery

These are reserved for inadequate response to first-line measures

Experimental and Investigational

Aetna considers the following interventions experimental and investigational for treatment of actinic keratoses because safety and effectiveness have not been established:

Listed experimental therapies: Cream containing sunscreen, piroxicam and a retinoic/glycolic gel; intense pulsed light; lapatinib; microneedling; microwave therapy; non-ablative fractional thulium laser; thermal photodynamic therapy; topical calcipotriol; topical piroxicam; topical vitamin D and analogs

Repetitive daylight PDT is also considered experimental/investigational for prevention of actinic keratoses

Clinical coverage-related evidence and scenarios

Evidence and guideline-aligned scenarios supported by the document:

Ingenol mebutate efficacy: Ingenol mebutate gel applied for 2–3 days demonstrated significantly higher complete clearance versus placebo for face/scalp and trunk/extremities in randomized trialsface/scalp: 42.2% vs 3.7%; trunk/extremities: 34.1% vs 4.7%

Local reactions peak early and resolve typically by day 29

PDT efficacy: Photodynamic therapy with 5-ALA or MAL shows higher participant and lesion clearance versus placebo-PDT and, in some trials, superiority over alternative formulations (e.g., BF-200 ALA vs MAL)BF-200 ALA: patient clearance 78.2% vs 17.1% (trial); pooled ALA/MAL-PDT participants cleared per 1,000: 527–656 vs 89–147 for placebo

Efficacy dependent on photosensitizer formulation and light source

When PDT is clinically appropriate: PDT may be used for multiple or field AK lesions, superficial and confluent AKs, or when other therapies are less appropriate or have failed

Evidence-informed coverage considerations

Evidence summaries and comparative findings that could inform coverage decisions:

Field-directed treatments vs vehicle/placebo: Randomized trials and meta-analyses show participant complete clearance significantly favored diclofenac/hyaluronic acid, 0.5% 5-FU, 5% imiquimod, and ingenol mebutate versus vehicle/placeboas reported in RCTs and Cochrane review

Consider adverse-event profiles and withdrawals when comparing treatments

Photodynamic therapy (PDT): PDT (ALA and MAL) shows significant benefit for lesion and participant clearance compared with placebo-PDT and may offer better cosmetic outcomes than cryotherapy; some trials favor ALA-PDT vs cryotherapyparticipant and lesion clearance measures per cited RCTs

Evidence in organ transplant recipients suggests MAL-PDT is best-studied in that group

Comparative ranking: Network meta-analysis ranked 5-FU highest, followed by ALA-PDT, imiquimod, ingenol mebutate, MAL-PDT, cryotherapy, diclofenac, then placebo; rankings should be interpreted with tolerability and other clinical considerations

Evidence summaries (no explicit coverage decision stated)

Evidence summaries and key findings

Micro-needling + PDT: Combination microneedling plus PDT showed a small mean additional lesion clearance (~6% more lesions cleared vs PDT alone) in heterogeneous low-quality RCTs; standardization and higher-quality trials are needed

UpToDate review does not mention MN+PDT

Microwave therapy: A small internally controlled randomized trial (11 subjects, 179 AKs) reported higher response in treated areas (90% vs 15% controls) with severe but brief pain; larger RCTs against effective comparators are needed

First-in-human feasibility data

Repetitive daylight PDT for prevention: A randomized multicenter study (58 patients) found fewer new AKs after repetitive daylight PDT than cryosurgery but the difference was not statistically significant; daylight PDT improved photo-aging signs and had less pain

Prevention efficacy not proven

The policy lists several technologies that are designated as experimental and investigational for treatment of actinic keratoses because safety and effectiveness have not been established. These include thermal photodynamic therapy, intense pulsed light (IPL), non-ablative fractional thulium laser, microneedling, microwave therapy, and other specified modalities. CPT/HCPCS coding guidance in the document flags these interventions as not covered for the CPB indications when they are listed as investigational (no specific procedure codes apply to those listed items).

Photodynamic therapy using established topical photosensitizers (e.g., aminolevulinic acid 10% gel or 20% solution, methyl aminolevulinate) is described elsewhere in the policy as an accepted option in defined circumstances, but thermal PDT (distinct device/technique) is specifically singled out among investigational approaches.

The document notes limited evidence that any AK treatment reduces progression to invasive squamous cell carcinoma (SCC). Systematic reviews and trials of photodynamic therapy and other interventions are limited by short follow-up durations and there are no conclusive data demonstrating long-term prevention of SCC, which constrains claims about durable chemoprevention.

Because long-term outcomes (including reduction in subsequent invasive SCC) are not well established in the trials and reviews cited, the policy treats prevention of progression as an evidence gap rather than a demonstrated benefit.

Topical vitamin D analogs and topical piroxicam are discussed as having insufficient or unsupported evidence for treatment of AK. A systematic review of off-label topical vitamin D analogs reported that topical vitamin D is ineffective for AK, and commentary on topical piroxicam notes that further controlled trials are needed and that major clinical reviews (UpToDate) do not list piroxicam as an established AK therapy.

Accordingly, these agents are listed among interventions considered investigational or not supported by current evidence for AK indications in this policy.

Some modalities have preliminary or early-phase evidence but remain insufficiently validated for routine coverage. Combination micro-needling plus PDT showed a small additional mean lesion clearance (~6% more lesions cleared versus PDT alone) in pooled, heterogeneous RCTs, but studies were low quality and protocols lacked standardization.

Microwave therapy produced promising results in a small randomized internally controlled trial (179 AKs in 11 subjects) with higher response in treated areas versus controls, but the study’s small sample size, short follow-up, and feasibility design mean larger randomized trials against effective comparators are needed before it can be considered established.

The policy explicitly identifies repetitive daylight photodynamic therapy as experimental and investigational for prevention of actinic keratoses because effectiveness for prevention has not been established. A cited randomized multicenter trial failed to show a statistically significant reduction in new AKs compared with cryosurgery, despite improvements in photo-aging measures and lower pain.

Within the provided excerpts there are no statements framed as an explicit blanket "not medically necessary" determination separate from the experimental/investigational listings. The policy distinguishes interventions supported as medically necessary, those reserved after failure of first-line therapies, and a set of interventions characterized as experimental/investigational due to insufficient evidence.

A systematic review of off-label uses concluded that topical vitamin D analogs are ineffective for actinic keratoses. The policy therefore lists topical vitamin D and analogs among interventions without supportive evidence and treats them as investigational for AK treatment.

Coding

Covered CPT Codes (if selection criteria met)CPTCovered

11300	Shaving of epidermal or dermal lesion, single lesion, trunk, arms or leg; lesion diameter 0.5 cm or less.
11301	Shaving of epidermal or dermal lesion, lesion diameter 0.6 to 1.0 cm.
11302	Shaving of epidermal or dermal lesion, lesion diameter 1.1 to 2.0 cm.
11303	Shaving of epidermal or dermal lesion, lesion diameter over 2.0 cm.
11305	Shaving of epidermal or dermal lesion, single lesion, scalp, neck, hands, feet, genitalia; lesion diameter 0.5 cm or less.
11306	Lesion diameter 0.6 to 1.0 cm.
11307	Lesion diameter 1.1 to 2.0 cm.
11308	Lesion diameter over 2.0 cm.
11310	Shaving of epidermal or dermal lesion, single lesion, face, ears, eyelids, nose, lips, mucous membrane; lesion diameter 0.5 cm or less.
11311	Lesion diameter 0.6 to 1.0 cm.

1–10 of 41

1/5

Photodynamic therapy CPT codesCPTCovered

96567	Photodynamic therapy by external application of light to destroy pre-malignant and/or malignant lesions of the skin and adjacent mucosa, each phototherapy exposure session.
96573	Photodynamic therapy with application and illumination/activation of photosensitizing drug(s) provided by a physician or other qualified health care professional, per day.

HCPCS codes for topical photosensitizersHCPCSCovered

J7308	Aminolevulinic acid HCL for topical administration, 20%, single unit dosage form (354 mg).
J7345	Aminolevulinic acid hcl for topical administration, 10% gel, 10 mg.
J7309	Methyl aminolevulinate (MAL) for topical administration, 16.8%, 1 gram [discontinued].

ICD-10 CodesICD-10

L57.0

Actinic keratosis

CPT/HCPCS codes not covered for listed indicationsmixedNot Covered

Thermal PDT / IPL / non-ablative fractional thulium laser / microneedling / microwave therapy / repetitive daylight PDT

No specific CPT/HCPCS code - interventions listed as not covered for indications in this CPB.

Referenced PDT products/devicesmixed

Levulan Kerastick (20% ALA)	FDA-approved drug/device combination for PDT (brand/product referenced).
Ameluz (aminolevulinic acid gel, 10%)	Approved in combination with BF-RhodoLED for lesion- and field-directed treatment of mild-to-moderate AKs of the face and scalp.
Metvixia (methyl aminolevulinate cream, 16.8%)	Previously marketed product (withdrawn from U.S. market as noted).

No explicit billing or procedural codes in these chunksmixed

No codes listed

Number of lesions — CPT codes (lesion counts)

CPT code — first lesion17000: Destruction, premalignant lesions; first lesion

CPT code — 2 to 14 lesions17003: Second through 14 lesions, each

CPT code — 15 or more lesions17004: 15 or more lesions

Provider Actions and Operational Notes

Prior Authorization

Prior authorization / Coding and denial risk

CPT and HCPCS codes for photodynamic therapy (PDT) and related products are payable only when the selection and medical‑necessity criteria in this policy are met. Codes for interventions listed as experimental/investigational in this policy may be denied.

Covered HCPCS: J7308 (ALA 20%), J7345 (ALA 10% gel) — only if policy criteria met.
Disallowed/Investigational techniques (no specific CPT/HCPCS codes): thermal PDT, repetitive daylight PDT, intense pulsed light, microwave therapy, microneedling, non-ablative fractional thulium laser.

Note

Prior authorization — administrative note

This excerpt does not specify a formal payer prior authorization requirement for PDT or other AK treatments. Where prior authorization processes exist at the plan level, providers must follow the payer’s routine prior authorization workflows.

No explicit prior authorization rules listed in this policy excerpt.
Verify member benefits and any plan-level prior authorization requirements before treatment.

Note

Prior authorization — evidence‑informed guidance

Evidence-informed guidance in the clinical background supports using PDT (ALA or MAL) as an option for patients with extensive or refractory AKs and for certain high‑risk populations (e.g., organ transplant recipients). The policy does not establish step‑therapy requirements but summarizes evidence that may inform clinical decision-making.

Guideline-style recommendations: PDT may be reserved for extensive AKs not controlled with cryotherapy or topical 5‑FU.
No formal step therapy mandated by this policy; evidence may favor 5‑FU or PDT ahead of less-studied modalities.

Prior Authorization

PDT (ALA) prior authorization and documentation considerations

Specific clinical/operational considerations for topical ALA PDT (e.g., Ameluz 10% gel) should be documented when used, particularly for large‑area treatments. Documents should support the indication, treatment area, and expected post‑treatment care to help substantiate medical necessity.

Record treated surface area (noting studies reporting use up to 75–300 cm2).
Document product used (ALA 10% gel vs ALA 20% solution), light source (blue or red), incubation time, and post‑PDT care instructions.
Note if treatment is lesion‑directed or field‑directed and rationale (e.g., extensive or refractory AKs, organ transplant recipient).

Denial Risk

Denial risk — evidence limitations

Evidence limitations for newer or less‑studied interventions (small trials, first‑in‑human studies, or techniques listed as investigational) may lead to claim denials or coverage exclusions. Providers should cite RCT data or guideline support when available.

Interventions considered investigational by this policy (may trigger denial): thermal photodynamic therapy, repetitive daylight PDT for prevention, microwave therapy (pending larger RCTs), microneedling, topical agents lacking evidence.
Provide trial identifiers, peer‑reviewed publications, and rationale when requesting coverage for less-established treatments.

Note

Provider responsibility — policy scope and benefit verification

Clinical Policy Bulletins (CPBs) summarize clinical evidence and coverage positions but do not guarantee payment. Providers remain responsible for verifying member benefits, obtaining any required authorizations, and for treatment decisions.

CPB content is informational and may be updated; always confirm plan-specific coverage and benefit design.
Obtain prior authorization if required by the member’s plan and document medical necessity in the record.

Documentation Required

Specimen submission when carcinoma suspected

When curettage or excision is performed because invasive squamous cell carcinoma (SCC) is suspected, submission of the specimen for histologic analysis is required and should be documented in the medical record.

Include pathology report or specimen submission documentation in the patient record when SCC is suspected.
Curettage/excision for suspected carcinoma is considered medically necessary when histologic analysis is indicated.

Documentation Required

No explicit documentation/authorization workflow provided

This excerpt does not list explicit documentation or authorization steps beyond standard medical-record documentation and plan-level prior authorization processes. Clinical justification (lesion characteristics, prior therapies tried, and rationale for modality choice) should be included in requests.

Document prior treatments and responses (e.g., prior cryotherapy, topical 5‑FU or imiquimod) when seeking coverage for alternative modalities.
State lesion location, size, number, and whether lesion‑directed or field‑directed therapy is required.

Documentation Required

Evidence documentation expectations

Summarize and cite relevant evidence when requesting coverage for treatments. The policy references systematic reviews, network meta-analyses, RCTs, and guideline statements as the basis for recommendations and coverage positions.

Preferred supporting evidence: RCTs, Cochrane or systematic reviews, guideline recommendations (e.g., British Association of Dermatologists, European Dermatology Forum).
Include lesion‑level and participant‑level outcome data when available (clearance rates, adverse events).

Documentation Required

Document treatment area and post‑PDT care

For large-area PDT treatments, document the exact area treated and the post‑PDT care regimen provided and followed by the patient (e.g., zinc oxide, healing creams, sun protection) because adverse effects and mitigation strategies are relevant to medical necessity and safety.

If treating >20 cm2 (FDA‑largest approved field for some products), include rationale for larger field and documentation of patient counseling and post‑treatment instructions.
Note any deviations from manufacturer‑recommended incubation or illumination protocols with clinical justification.

Step Therapy

Treatment sequencing and guideline‑style recommendations

Treatment sequencing considerations: cryosurgery, topical therapies (5‑FU, imiquimod, diclofenac, ingenol mebutate), and curettage/excision (when SCC suspected) are first‑line options. PDT is often considered for extensive or refractory AKs; no formal step‑therapy requirements are specified in this policy excerpt.

Consider 5‑FU or imiquimod for field therapy, especially in organ transplant recipients where RCT data support topical agents.
PDT may be preferred for superficial, confluent, or extensive lesions not controlled by standard therapies.

Note

Policy history and versioning

Policy history and review dates are provided in the policy header; ensure requests reflect the current policy effective date and most recent review.

Policy Effective Date: 11/09/2001; Last Review: 08/10/2023; Next Review: 06/13/2024.
Use current policy version when preparing prior authorization or coverage justification.

Definitions

Actinic keratosis (AK) — definition and description

DefinitionActinic keratosis (AK): sun-induced, pre-cancerous epidermal lesion presenting as circumscribed rough, scaly patches on sun-exposed skin that may progress to squamous cell carcinoma

Typical locationsFace, head, neck, forearms, hands, upper back (actinic cheilitis is a variant on the lip)

Risk factors/importanceMore common in fair-skinned individuals, increases with age, male sex, immunosuppression, and prior skin cancer history; prevalence reported 23–61.1%

Cryosurgery with liquid nitrogen — definition and practice notes

DefinitionCryosurgery with liquid nitrogen: lesion-directed destructive procedure applying liquid nitrogen to freeze and slough AK lesions

Typical practice notesUsually used for discrete AKs; generally does not require local anesthetic and involves mild pain and transient post-procedural erythema

When indicatedAppropriate for isolated, discrete lesions rather than extensive field disease

Ingenol mebutate — definition and mechanism/usage notes

DefinitionIngenol mebutate: topical field therapy applied for 2–3 days (0.015% for face/scalp; 0.05% for trunk/extremities) for treatment of AKs

Mechanism and usageDual mechanism: rapid lesion necrosis plus neutrophil-mediated, antibody-dependent cellular cytotoxicity; short course therapy targets residual dysplastic cells after necrosis

Efficacy noteRandomized trials showed higher complete clearance versus placebo (face/scalp 42.2% vs 3.7%; trunk/extremities 34.1% vs 4.7%) with local reactions peaking early and resolving by ~day 29

Photodynamic therapy (PDT) — definition and components

DefinitionPhotodynamic therapy (PDT): a two-step treatment using a topical photosensitizing agent applied to lesions and activation with a specific light source to destroy atypical cells

ComponentsPhotosensitizer (e.g., 5-ALA, aminolevulinic acid; methyl aminolevulinate/MAL) plus light source (blue or red light; device examples: BLU-U, BF-RhodoLED)

Practice notesPhotosensitizer applied and, after incubation (e.g., 14–18 hours for 5-ALA), lesion is illuminated; common side effects include erythema, stinging/burning, edema, scaling/crusting; treatment typically requires a multi-day protocol

Curettage — definition and role

DefinitionCurettage: destructive scraping technique using a curette to remove lesions, treating to a deeper dermal level than cryosurgery

RoleIndicated for larger lesions and lesions in immunocompromised patients; allows submission of specimen for histologic analysis when invasive SCC is suspected

Practical considerationsMay be combined with electrosurgery to control bleeding; requires local anesthesia and carries scarring risk

Participant complete clearance — trial outcome definition

DefinitionParticipant complete clearance: the trial primary outcome defined as complete clearance of all target AK lesions in a participant as reported in RCTs and meta-analyses

Use in evidence synthesesUsed across RCTs and Cochrane reviews to compare efficacy of field-directed and lesion-directed therapies (e.g., reported for ingenol mebutate, PDT, 5-FU, imiquimod)

Reporting implicationsEffect sizes and network rankings are based on participant complete clearance and inform comparative effectiveness conclusions

Organ transplant recipients (OTRs) — definition and high-risk relevance

DefinitionOrgan transplant recipients (OTRs): chronically immunosuppressed patients after organ transplantation who are at high risk for progression of AK to invasive squamous cell carcinoma

Relevance to treatment selectionField-directed regimens (e.g., MAL-PDT, 5-FU, imiquimod, diclofenac) are preferred in OTRs; MAL-PDT is the best-studied intervention in RCTs for this group

Evidence noteLimited RCT evidence in OTRs (8 RCTs, 242 OTRs) suggests higher participant complete clearance with MAL-PDT (40–76.4%) compared with other modalities

Field-directed therapy — definition and examples

DefinitionField-directed therapy: treatment applied to a photodamaged area to address multiple visible and subclinical AKs rather than single lesions

ExamplesPhotodynamic therapy (PDT), topical field regimens such as 5‑fluorouracil (5‑FU), imiquimod, diclofenac/hyaluronic acid, and ingenol mebutate

PurposeAims to treat both clinical and subclinical lesions across a field and may reduce development of new lesions; choice influenced by extent of photodamage and patient risk factors

OpenPayer

Actinic Keratoses Treatments

Coverage Criteria

Coding

Provider Actions and Operational Notes

Background

Definitions

Revision History