Medical Policy: 02.01.16
Original Effective Date: January 2002
Reviewed: February 2017
Revised: March 2015
Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.
This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.
Photodynamic therapy (PDT) is a medical procedure that involves the administration of a photosensitizing drug and subsequent exposure to a light source to induce cellular damage. Photodynamic therapy (PDT) has been investigated for the treatment of actinic keratosis, non-melanoma skin cancers, acne vulgaris, mycoses, and hidradenitis suppurativa.
Photodynamic therapy is a two-step process and typically involves two office visits spaced a week apart. More than one treatment series may be required. In step one the medication is topically applied to the affected tissue and allowed to absorb for a set period of time. The drug accumulates and is retained in dysplastic cells of the skin to a greater degree than normal tissue (i.e. the drug has a greater affinity for dysplastic cells. In step two, the affected skin tissue is exposed to the light source. The photoactivation of the drug creates a cytotoxic reaction within the cells that destroys dysplastic lesions. The cytotoxic effect is dependent on light and oxygen. Two common photosensitizing agents are 5-aminolevulinac acid (5-ALA) and methyl aminolevulinate (MAL). PDT can cause erythema, burning, and pain. Healing occurs within 10 to 14 days, with generally acceptable cosmetic results.
Actinic keratoses is the most common premalignant skin condition. The rough scaly plaques are the direct result of damage from ultraviolet light and other carcinogenic exposures. It is commonly seen on the sun-exposed skin of elderly patients with fair complexions. In some cases, actinic keratoses may progress to squamous cell carcinoma (SCC). The available treatments for actinic keratoses can generally be divided into surgical and non-surgical methods. Surgical treatments used to treat one or a small number of dispersed individual lesions include excision, curettage (either alone or combined with electrodessication), and laser surgery. Non-surgical treatments include cryotherapy, topical chemotherapy (5-fluorouracil [5-FU] or masoprocol creams), chemexfoliation (also known as chemical peels), and dermabrasion. Topical treatments are generally used in patients with multiple lesions and the involvement of extensive areas of the skin. Under some circumstances, combinations of different treatment methods may be used.
Several RCTs have compared different approaches to applying PDT in the treatment of actinic keratosis. Evidence from multiple RCTs has found that PDT improves net health outcome in patients with non-hyperkeratotic actinic keratosis of the face and scalp compared with placebo or other active interventions. The evidence is sufficient to determine there is a meaningful improvement in the net health outcome.
Non-melanoma skin cancers are the most common malignancies in the Caucasian population. Basal cell carcinoma (BCC) is most often found in light-skinned individuals and is the most common of the cutaneous malignancies. Although BCC tumors rarely metastasize, they can be locally invasive if left untreated, leading to significant local destruction and disfigurement. The most prevalent forms of BCC are nodular BCC and superficial BCC. Bowen's disease is a squamous cell carcinoma (SCC) in situ with the potential for significant lateral spread. Metastases are rare, with less than 5% of cases advancing to invasive SCC. Lesions may appear on sun-exposed or covered skin. Excision surgery is the preferred treatment for smaller non-melanoma skin lesions and those not in problematic areas, such as the face and digits. Other established treatments include topical 5-fuorouracil, topical imiquimod, and cryotherapy. Poor cosmesis resulting from surgical procedures and skin irritation induced by topical agents can be significant problems.
For individuals who have low risk basal cell carcinoma (BCC) who receive PDT, the evidence includes RCTs and systematic reviews of RCTs. Systematic reviews of RCTs have found that PDT may not be as effective as surgery for superficial and nodular BCC. In the small number of trials available, PDT was more effective than placebo. The available evidence from RCTs has suggested that PDT has better cosmetic outcomes than surgery. The evidence is sufficient to determine that PDT results in a meaningful improvement in the net health outcome.
For individuals who have squamous cell carcinoma in-situ (Bowen’s disease) who receive PDT, the evidence include RCTs. The RCTs have found that PDT has similar or greater efficacy compared with cryotherapy and 5-fluorouracil. Additionally, adverse events/cosmetic outcomes appear to be better after PDT. Few RCTs have compared PDT with surgery or radiotherapy. However, based on the evidence of the RCTs, PDT may be utilized when surgery and radiation are contraindicated. The evidence is sufficient to determine that PDT results in a meaningful improvement in net health outcome.
There is evidence from randomized controlled trials (RCTs) that photodynamic therapy (PDT) is an effective treatment for selected patients with non-hyperkeratotic actinic keratoses of the face and scalp compared with placebo or cryotherapy. The evidence to date suggests that PDT is less effective than surgery and radiotherapy and of similar efficacy to cryotherapy for treating low-risk basal cell carcinoma (BCC) (e.g. superficial or nodular). Moreover, the evidence suggests that cosmetic outcomes are better after PDT compared with surgery and cryotherapy. Evidence from RCTs suggest that, in patients with Bowen disease (BD), PDT has similar or higher efficacy compared with cryotherapy and 5-fluorouacil (5-FU), and better cosmetic outcomes. Therefore, PDT may be considered medically necessary for treating non-hypertonic actinic keratosis of the face and scalp and for treating low-risk BCC and Bowen's disease when surgery and radiation are contraindicated. The evidence is sufficient to determine that PDT results in meaningful improvement in net health outcomes for these indications.
No controlled studies using FDA approved photosensitizing agents for PDT in other dermatologic indications (i.e. acne vulgaris, hidradenitis suppurativa, mycoses, warts) have been identified. Only case series were found. RCTs are needed to determine the safety and efficacy of PDT for these other dermatologic indications. Therefore, there is insufficient evidence that PDT improves the net health outcomes for all other dermatologic conditions compared with accepted treatments and is considered investigational.
Principles of Treatment for Basal Cell Skin Cancers
PDT involves the application of a photosensitizing agent on the skin followed by irradiation with a light source. Photosensitizing agents often used include methyl aminolevulinate (MAL) and 5-aminolevulinic acid (ALA). These two agents have similar efficacy outcomes and pain scores when used to treat patients with nodular BCC. Multiple randomized trials and a meta-analysis including 4 of these trials have shown that rates of excellent or good cosmetic outcomes were higher with PDT versus surgery, even though surgery was superior to PDT in terms of efficacy (complete clearance, 1 year and 5 year recurrence rates).
Principles of Treatment for Squamous Cell Skin Cancer
Since cure rates may be lower, superficial therapies should be reserved for those patients where surgery or radiation is contraindicated or impractical. Superficial therapies include topical treatment with topical 5-FU or topical imiquimod, photodynamic therapy (PDT) and cryotherapy.
The International Society for Photodynamic Therapy in Dermatology published consensus based guidelines on the use of photodynamic therapy (PDT) for non-melanoma skin cancer in 2005.
Levulan® Kerastick™ is a topical preparation of ALA used in conjunction with illumination with the BLU-U™ Blue Light Photodynamic Therapy Illuminator, a blue light source. It is approved by the U.S. Food and Drug Administration (FDA) for the treatment of non-hyperkeratotic actinic keratoses of the face and scalp. The product is applied in the physician's office.
Another variant of PDT for skin lesions is Metvixia® and the Aktilite CL 128 lamp, each of which received FDA approval in 2004. Metvixia consists of the topical application of methyl aminolevulinate (MAL) followed by exposure with the Aktilite CL 128 lamp, a red light source. Metvixia is indicated for the treatment of non-hyperkeratotic actinic keratoses of the face and scalp in immunoincompetent patients when used in conjunction with lesion preparation (sharp debridement) in the physician's office when other therapies are unacceptable or considered medically less appropriate.
A 5-aminoleveulinic acid patch technology (5-ALA Patch) is available outside of the U.S. through an agreement between Intendis (part of Bayer HealthCare) and Photonamic GmbH and Co. KG. The 5-ALA patch is not approved by the FDA.
Photodynamic therapy may be considered medically necessary as a treatment of:
Photodynamic therapy is considered investigational for other dermatologic applications, including, but not limited to the following:
No high-quality comparative studies have evaluated photodynamic therapy for acne or other dermatologic conditions. RCTs are needed to determine safety and efficacy of PDT for these conditions. The evidence is insufficient to show that photodynamic therapy improves net health outcomes for all other conditions except as indicated above and therefore would be considered investigational.
Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc. They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.
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