Latest Review Date: December 2023

Category: Medical  

POLICY:

Photodynamic therapy with a FDA approved agent may be considered medically necessary in the treatment of multiple (greater than 10 lesions) non-hyperkeratotic actinic keratosis of the chest, face, scalp, neck, and upper extremities. Treated lesions that have not completely resolved after 8 weeks may be treated a second time.

Photodynamic therapy with a FDA approved agent may be considered medically necessary for severe hidradenitis suppurativa (HS).

Photodynamic therapy with a FDA approved agent may be considered medically necessary in the treatment of low-risk (e.g., superficial and nodular) basal cell skin cancer (BCC) only when surgery and radiation are contraindicated.

Photodynamic therapy with a FDA approved agent may be considered medically necessary in the treatment of Bowen’s disease (squamous cell carcinoma in situ) only when surgery and radiation are contraindicated.

Photodynamic therapy with a FDA approved agent is considered investigational when performed for other dermatologic applications, including, but not limited to, squamous cell carcinoma (excluding Bowen’s disease), high-risk basal cell carcinoma, acne vulgaris, and mycoses.

Photodynamic therapy as a technique of skin rejuvenation, hair removal, or other cosmetic indications is considered not medically necessary.

DESCRIPTION OF PROCEDURE OR SERVICE:

Photodynamic therapy (PDT) refers to light activation of a photosensitizer to generate highly reactive intermediaries, which ultimately cause tissue injury and necrosis. Photosensitizing agents are being proposed for use with dermatologic conditions such as actinic keratoses (AKs) and nonmelanoma skin cancers.

Photodynamic Therapy

Photodynamic therapy (PDT) refers to light activation of a photosensitizer to generate highly reactive intermediaries, which ultimately cause tissue injury and necrosis. Two common photosensitizing agents are 5-aminolevulinic acid (ALA) and its methyl ester, methyl aminolevulinate. When applied topically, these agents pass readily through abnormal keratin overlying the lesion and accumulate preferentially in dysplastic cells. The agents ALA and methyl aminolevulinate are metabolized by underlying cells to photosensitizing concentrations of porphyrins. Subsequent exposure to photoactivation (maximum absorption at 404 to 420 nm and 635 nm) generates reactive oxygen species that are cytotoxic, ultimately destroying the lesion. PDT can cause erythema, burning, and pain. Healing occurs within ten to fourteen days, with generally acceptable cosmetic results. PDT with topical ALA has been investigated primarily as a treatment of AKs.

KEY POINTS:

The most recent literature was reviewed through October 11, 2023.

Summary of Evidence

For individuals who have nonhyperkeratotic AK on the face or scalp who receive PDT, the evidence includes meta-analyses and randomized controlled trials (RCTs). Relevant outcomes are symptoms, change in disease status, quality of life (QOL), and treatment-related morbidity. Evidence from multiple RCTs has found that PDT improves the net health outcome as measured by complete clinical clearance of lesions in individuals with nonhyperkeratotic AK on the face or scalp compared with placebo or other active interventions. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have nonhyperkeratotic AKs on the upper extremities who receive PDT, the evidence includes a systematic review and RCTs. Relevant outcomes are symptoms, change in disease status, QOL, and treatment-related morbidity. A systematic review of interventions for nonface and nonscalp AKs found PDT to be superior to placebo for complete clearance, but found a significant increase in complete clearance with cryotherapy versus PDT. In 2 placebo-controlled RCTs, significantly more individuals had a complete clearance of AKs with 5-aminolevulinic acid (ALA)/PDT with blue light compared to placebo at twelve weeks, and a third found a significantly greater reduction in mean lesion count at 4 weeks. Two small RCTs compared ALA/PDT using red light to imiquimod or 5-fluorouracil and found similar efficacy between the active treatment groups after 6 months of follow-up. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have low-risk basal cell carcinoma who receive PDT, the evidence includes RCTs and systematic reviews of RCTs. Relevant outcomes are symptoms, change in disease status, QOL, and treatment-related morbidity. Systematic reviews of RCTs have found that PDT may not be as effective as surgery for low-risk superficial and nodular basal cell carcinoma. In the small number of trials available, PDT was more effective than a placebo. The available evidence from RCTs has suggested that PDT has better cosmetic outcomes than surgery for low-risk basal cell carcinoma. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have squamous cell carcinoma in situ who receive PDT, the evidence includes meta-analyses and RCTs. The relevant outcomes are symptoms, change in disease status, QOL, and treatment-related morbidity. Meta-analysis and RCTs have found that PDT has similar or greater efficacy compared with cryotherapy and 5-fluorouracil. Additionally, adverse events and cosmetic outcomes appear to be better after PDT. Few RCTs have compared PDT with surgery or radiotherapy; as a result, conclusions cannot be drawn about PDT compared with these other standard treatments. Current guidance from the National Comprehensive Cancer Network notes that topical modalities, including PDT, may have lower cure rates than with surgical treatment. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have nonmetastatic invasive squamous cell carcinoma who receive PDT, the evidence includes observational studies and a systematic review of observational studies. Relevant outcomes are overall survival, symptoms, change in disease status, quality of life, and treatment-related morbidity. Conclusions cannot be drawn from small, uncontrolled studies. RCTs are needed to determine the safety and efficacy of PDT for this condition. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have acne who receive PDT, the evidence includes RCTs and systematic reviews. Relevant outcomes are symptoms, change in disease status, QOL, and treatment-related morbidity. The available RCTs have not consistently found significantly better outcomes with PDT compared with other interventions, and meta-analyses did not find significantly better results with PDT versus placebo. Several trials have found that PDT is associated with high rates of adverse events leading to the cessation of treatment. Trials tended to have relatively small sample sizes and used a variety of comparison interventions. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have noncancerous dermatologic skin conditions (e.g., hidradenitis suppurativa, mycoses, port-wine stain) who receive PDT, the evidence includes case series, systematic reviews of uncontrolled series, and an RCT for port-wine stain. Relevant outcomes are symptoms, change in disease status, QOL, and treatment-related morbidity. RCTs are needed to determine the safety and efficacy of PDT for these conditions. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Practice Guidelines and Position Statements

American Academy of Dermatology

The American Academy of Dermatology has guidelines addressing use of photodynamic therapy (PDT) in actinic keratosis (AK), basal cell carcinoma, and acne:

• Actinic keratosis (2021): PDT is included in the following recommendations for individuals with AK:
  • 5-aminolevulinic acid (ALA)-red light PDT is conditionally recommended (low quality of evidence)
  • ALA-daylight PDT is conditionally recommended as less painful than but equally effective as ALA-red light PDT (moderate quality of evidence)
  • ALA-blue light PDT is conditionally recommended (moderate quality of evidence)
  • ALA-red light PDT is conditionally recommended over cryosurgery alone (low quality of evidence)
• Basal cell carcinoma (2018): Use of topical therapies, including PDT, is most appropriate for low-risk basal cell carcinoma when surgery is impractical or declined by the individual. Discussions of the relative effectiveness of topical therapies should be discussed with the individual. The guideline further notes that "Cure rates after surgical excision are 10% to 20% higher than those for topical therapies, including PDT, with excision associated with recurrence rates of less than 5%. Surgical excision may also be less painful and better tolerated."
• Acne (2016, update expected in 2023): More studies are needed on the use of PDT or other laser/light devices. PDT has the most evidence among laser/light devices for treating acne, but "additional studies are needed to determine the optimal photosensitizer, incubation time, and light source."

National Comprehensive Cancer Network

For treatment of precancers (diffuse AK, field cancerization, and cutaneous squamous cell carcinoma prophylaxis), the National Comprehensive Cancer Network (NCCN) (squamous cell skin cancer, v. 1.2023) made the following recommendations: "Accepted treatment modalities include cryotherapy, topical 5-fluorouracil (5-FU)(preferred) with or without calcipotriol (calcipotriene), topical imiquimod, topical tirbanibulin, photodynamic therapy (e.g., aminolevulinic acid, porfimer sodium), and curettage and electrodesiccation. For hyperkeratotic AK, pretreatment with topical tazarotene, curettage, or topical keratolytics (topical urea, lactic acid, and salicylic acid) prior to above therapies may be considered.

For squamous cell skin cancers, the NCCN (squamous cell skin cancer, v. 1.2023) made the following recommendations: “In patients with SCC [squamous cell carcinoma] in situ (Bowen’s disease) alternative, therapies such as topical 5-fluorouracil, topical imiquimod, photodynamic therapy (e.g., ALA, porfimer sodium), or vigorous cryotherapy may be considered, even though the cure rates may be lower than with surgical treatment modalities.”

For basal cell skin cancer, NCCN (v.2.2022) made the following recommendations: “In individuals with superficial basal cell skin cancer, therapies such as topical 5-fluorouracil, topical imiquimod, photodynamic therapy, or cryotherapy may be considered, even though the cure rates are approximately 10% lower than with surgical treatment modalities.”

United States and Canadian Hidradenitis Suppurativa Foundations

A joint guideline from the United States and Canadian Hidradenitis Suppurativa Foundations (2019) provides guidance on diagnosis and complementary and procedural management of hidradenitis suppurativa. The guideline recommends PDT at a level C (based on consensus, opinion, case studies, or disease-oriented evidence). The authors state that PDT has a limited role in managing hidradenitis suppurativa, mainly due to a lack of large, well-controlled studies.

U.S. Preventive Services Task Force Recommendations

Not applicable.

KEY WORDS:

Photodynamic therapy, PDT, LEVULAN® KERASTICK® Levulan photodynamic therapy, Blue light therapy, BLU-U®, Blue light photodynamic therapy, ALA therapy, 5-ALA, Metvixia® and the CureLight BroadBand, 5-ALA Patch, ALA Topical Solution, 5-aminolevulinic acid patch technology, Aktilite® CL128 lamp, actinic keratoses, Bowen’s disease, Ameluz®, aminolevulinic acid hydrochloride (hcl).

APPROVED BY GOVERNING BODIES:

In 1999, LEVULAN® KERASTICK® a topical preparation of ALA, in conjunction with illumination with the BLU-U® Blue Light Photodynamic Therapy Illuminator, was approved by the U.S. Food and Drug Administration (FDA) for the treatment of nonhyperkeratotic actinic keratoses (AK) of the face and scalp. In 2018, the indication was expanded to include nonhyperkeratotic AKs of the upper extremities. The product is applied in the physician’s office.

In 2016, the FDA approved Ameluz® (aminolevulinic acid hydrochloride) gel, 10% (BF-200 ALA; Biofrontera AG) in combination with PDT using BF-RhodoLED lamp, to be used for the lesion-directed and field-directed treatment of AK of mild-to-moderate severity on the face and scalp. The treatment is to be administered by a healthcare provider.

ALApatch technology is available outside of the United States through an agreement between Intendis (part of Bayer HealthCare) and Photonamic. The ALA patch is not approved by the FDA.

Another variant of PDT for skin lesions is Metvixia® and the Aktilite CL128 lamp, each of which received FDA approval in July 2004. Metvixia® (Galderma, SA, Switzerland; PhotoCure ASA, Norway) consists of the topical application of MAL (in contrast to ALA used in the Kerastick™ procedure), followed by exposure with the Aktilite CL128 lamp, a red light source (in contrast to the blue light source in the LEVULAN® KERASTICK® procedure). Broadband light sources (containing the appropriate wavelengths), intense pulsed light (FDA product code: ONF), pulsed dye lasers, and potassium-titanyl-phosphate lasers have also been used. Metvixia® is indicated for the treatment of nonhyperkeratotic AK of the face and scalp in immunocompetent individuals when used with lesion preparation (debridement using a sharp dermal curette). The treatment must take place in the physician's office; moreover, the treatments must only be considered once all other therapies have been deemed unacceptable or no longer medically appropriate.

BENEFIT APPLICATION:

Coverage is subject to the member’s specific benefits.  Group-specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply

FEP contracts: Special benefit consideration may apply.  Refer to the member’s benefit plan.

CURRENT CODING:

CPT code:

96567	Photodynamic therapy by external application of light to destroy premalignant lesions of the skin and adjacent mucosa with application and illumination/activation of photosensitive drug(s), per day
96573	; provided by a physician or other qualified health care professional, per day
96574	Debridement of premalignant hyperkeratotic lesion(s) (i.e., targeted curettage, abrasion) followed with photodynamic therapy by external application of light to destroy premalignant lesions of the skin and adjacent mucosa with application and illumination/activation of photosensitizing drug(s) provided by a physician or other qualified health care professional, per day

HCPCS:

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

REFERENCES:

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28. Pariser DM, Lowe NJ, Stewart DM, et al. Photodynamic therapy with topical methyl aminolevulinate for actinic keratosis: results of a prospective randomized multicenter trial. J Am Acad Dermatol. Feb 2003; 48(2): 227-232.
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31. Reshetylo S, Narla S, Bakker C, et al. Systematic review of photodynamic therapy for the treatment of hidradenitis suppurativa. Photodermatol Photoimmunol Photomed. Jan 2023; 39(1): 39-50.
32. Reynolds KA, Schlessinger DI, Vasic J, et al. Core Outcome Set for Actinic Keratosis Clinical Trials. JAMA Dermatol. Mar 01 2020; 156(3): 326-333.
33. Roozeboom MH, Aardoom MA, Nelemans PJ et al. Fractionated 5-aminolevulinic acid photodynamic therapy after partial debulking versus surgical excision for nodular basal cell carcinoma: a randomized controlled trial with at least 5-year follow-up. J Am Acad Dermatol 2013; 69(2):280-287.
34. Roozeboom MH, Arits AH, Mosterd K, et al. Three-year follow-up results of photodynamic therapy vs. Imiquimod vs. fluorouracil for treatment of superficial basal cell carcinoma: a single-blind, noninferiority, randomized controlled trial. J Invest Dermatol. Aug 2016; 136(8):1568-1574.
35. Rhodes LE, de Rie M, Enström Y, et al. Photodynamic therapy using topical methyl aminolevulinate vs surgery for nodular basal cell carcinoma: results of a multicenter randomized prospective trial. Arch Dermatol. Jan 2004; 140(1): 17-23.
36. Rhodes LE, de Rie MA, Leifsdottir R, et al. Five-year follow-up of a randomized, prospective trial of topical methyl aminolevulinate photodynamic therapy vs surgery for nodular basal cell carcinoma. Arch Dermatol. Sep 2007; 143(9): 1131-1136.
37. Roozeboom MH, Arits AHMM, Mosterd K, et al. Three-Year Follow-Up Results of Photodynamic Therapy vs. Imiquimod vs. Fluorouracil for Treatment of Superficial Basal Cell Carcinoma: A Single-Blind, Noninferiority, Randomized Controlled Trial. J Invest Dermatol. Aug 2016; 136(8): 1568-1574.
38. Salim A, Leman JA, McColl JH, et al. Randomized comparison of photodynamic therapy with topical 5-fluorouracil in Bowen's disease. Br J Dermatol. Mar 2003; 148(3): 539-543
39. Schmieder GJ, Huang EY, Jarratt M. A multicenter, randomized, vehicle-controlled phase 2 study of blue light photodynamic therapy with aminolevulinic acid HCl 20% topical solution for the treatment of actinic keratoses on the upper extremities: the effect of occlusion during the drug incubation period.. J Drugs Dermatol, 2013 Feb 5;11(12).
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41. Serra-Guillen C, Nagore E, Hueso L et al. A randomized pilot comparative study of topical methyl aminolevulinate photodynamic therapy versus imiquimod 5% versus sequential application of both therapies in immunocompetent patients with actinic keratosis: clinical and histologic outcomes. J Am Acad Dermatol. Apr 2012; 66(4):e131-e137.
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POLICY HISTORY:

Medical Policy Group, November 2000

Medical Review Committee, February 2001

TEC, November 2001

Medical Policy Group, March 2002

Medical Review Committee, May 2002

Medical Policy Administration Committee, June 2002

Available for comment June 17-July 31, 2002

Medical Policy Group, June 2004 (1)

Medical Policy Group, November 2005 (3)

Medical Policy Administration Committee, November 2005

Available for comment December 16, 2005-January 30, 2006

Medical Policy Group, January 2008 (3)

Medical Policy Administration Committee, February 2008

Available for comment February 21-April 4, 2008

Medical Policy Group, June 2010 (3)

Medical Policy Administration Committee, June 2010

Available for comment June 18-August 2, 2010

Medical Policy Group, December 2010 (1): 2011 Coding update, added J7309 to policy

Medical Policy Panel, January 2011

Medical Policy Group, September 2011 (2): Policy, Key Points, Key Words and References updated

Medical Policy Administration Committee, September 2011

Available for comment September 22 through November 7, 2011

Medical Policy Group, January 2012 (1): Update to Key Points and References related to MPP update; no change in policy statement

Medical Policy Panel, January 2013

Medical Policy Group, March 2013 (2): Policy statements unchanged; Key Points and References updated.

Medical Policy Panel, January 2014

Medical Policy Group, January 2014 (3):  Update to Key Points and References; no change in policy statement

Medical Policy Panel, January 2015

Medical Policy Group, January 2015 (3):  2015 Update to Key Points and References; policy statement verbiage clarification with no change in policy statement intent.

Medical Policy Panel, January 2016

Medical Policy Group, January 2016 (2): 2016 Updates to Description, Key Points, Key Words, and References, no change to policy statement.

Medical Policy Panel, December 2016

Medical Policy Group, December 2016 (7): 2016 Updates to Key Points, Key Words, References and Coding-  added J3490 to current coding. No change to policy statement.

Medical Policy Group, December 2017: Annual Coding Update 2018 - Added new CPT codes 96573 and 96574 effective 1/1/18 to Current Coding; Added new HCPCS code J7345 to Current Coding; Updated description to revised code 96567.

Medical Policy Panel, December 2017

Medical Policy Group, December 2017 (7): 2017 Updates to Key Points, Approved by Governing Bodies and References. No change to policy statement.

Medical Policy Group, February 2018 (7): Added Key Words: Ameluz, aminolevulinic acid hydrochloride (hcl). No change in Policy Statement.

Medical Policy Panel, December 2018

Medical Policy Group, January 2019 (7): Updates to Key Points and References. No change to policy statement.

Medical Policy Panel, December 2019

Medical Policy Group, January 2020 (5): Updates to Description, Key Points, Approved by Governing Bodies, Practice Guidelines and Position Statements, and References. Policy Statement verbiage modified for non-hyperkeratotic actinic keratosis of the chest, face, scalp, neck, forearms, and hands. Removed “forearms, and hands,” and replaced with “and upper extremities.” No change in Policy intent.

Medical Policy Panel, December 2020

Medical Policy Group, December 2020 (5): Updates to Description, Key Points, Practice Guidelines and Position Statements, and References. No change to Policy Statement.

Medical Policy Panel, December 2021

Medical Policy Group, December 2021 (5): Updates to Description, Key Points, Practice Guidelines and Position Statements, Approved by Governing Bodies, and References. Policy Statement updated to remove “investigational” and “not medically necessary,” no change to policy intent.

Medical Policy Panel, December 2022

Medical Policy Group, December 2022 (5): Updates to Description, Key Points, Practice Guidelines and Position Statements, Approved by Governing Bodies, and References. No change to Policy Statement.

Medical Policy Group, December 2023 (9): Updates to Description, Key Points, Key Words, Benefit Application, References and Coding-removed J3490 from current coding as not applicable to this policy anymore. No change to Policy Statement.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and   

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.