Medical Policy: 02.01.16
Original Effective Date: January 2002
Reviewed: February 2016
Revised: March 2015
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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) refers to light activation of a photosensitizer to generate highly reactive intermediaries, which ultimately cause tissue injury and necrosis. Photosensitizing agents, administered orally or intravenously, have been used in non-dermatologic applications and are being proposed for use with dermatologic conditions such as actinic keratoses and non-melanoma skin cancers.
Photodynamic therapy typically involves two office visits. One to apply the topical photosensitizing agent and a second visit to the expose the patient 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. Photodynamic protocols typically involve two treatments spaced a week apart, more then one treatment series may be required.
Two common photosensitizing agents are 5-aminolevulinac acid (5-ALA) and its methyl ester methyl aminolevulinate (MAL). When applied topically these agents pass readily through the abnormal keratin overlying the lesion and accumulate preferentially in dysplastic cells. 5-ALA and MAL are metabolized by the underlying cells to photosensitizing concentrations of porphyrins. Subsequent exposure to photoactivation (maximum absorption at 404-420 nm and 635 nm, respectively) generates reactive oxygen species that are cytotoxic, ultimately destroying the lesion. PDT can cause erythema, burning, and pain. Healing occurs within 10 to 14 days, with generally acceptable cosmetic results. PDT with topical ALA has been investigated primarily as a treatment of actinic keratoses. It has also been investigated as a treatment of other superficial dermatologic lesions such as Bowen's disease, acne vulgaris, mycoses, hidradenitis suppurativa, and superficial and nodular basal cell carcinoma. Potential cosmetic indications include skin rejuvenation and hair removal.
Actinic keratoses is the most common premalignant skin condition. The rough scaly plaques are the direct results of damage from ultraviolet light and other carcinogenic exposures. It is commonly seen on the sun-exposed skin of elderly patients with fair complexions. 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.
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 the 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, imiquimod, and cryotherapy. Poor cosmesis resulting from surgical procedures and skin irritation induced by topical agents can be significant problems.
There is evidence from randomized controlled trials (RCYTs) that photodynamic therapy (PDT) is an effective treatment for selected patients with 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 BD when surgery and radiation are contraindicated.
No controlled studies using FDA approved photosensitizing agents for PDT in other dermatologic indications have been identified. Only case series were found. 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.
Practice Guidelines and Position Statements
National Comprehensive Cancer Network (NCCN)
Version 1.2016 Basal Cell and Squamous Cell Skin Cancers
Principles of Treatment for Basal Cell Skin Cancers
• In patients with low risk, superficial basal cell skin cancer, where surgery or radiation is contraindicated or impractical, topical therapies such as 5-fluorouracil, imiquimod, photodynamic therapy (e.g. aminal levulinic acid (ALA), porfimer sodium) or vigorous cryotherapy may be considered,e ven thought the cure rate may be lower.
National Comprehensive Cancer Network (NCCN)
Version 1.2016 Squamous Cell Skin Cancer
Principles of Treatment for Squamous Cell Skin Cancer
• In patients with squamous cell carcinoma in situ (Bowen’s disease) that is low risk, alternative therapies such as 5-flurouracil, imiquimod, photodynamic therapy (e.g. amino levulinic acid (ALA), profimer sodium) or vigorous cryotherapy may be considered even though cure rate may be lower.
International Society for Photodynamic Therapy in Dermatology
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.
- Actinic Keratoses (AK): As PDT with either ALA or MAL is highly effective and offers excellent cosmetic outcome, it should be considered as a first-line therapy for AK (Rating: AI); MAL-PDT has a superior cosmetic outcome compared to cryotherapy (Rating: AI)
- Bowen’s Disease (BD): Topical PDT is effective in BD, achieving good cosmesis, and is at least as effective as cryotherapy or 5-fluorouacil, but with fewer adverse events; topical PDT should be considered as a first-line therapy for BD (Rating AI).
- Squamous Cell Carcinoma (SCC): There is insufficient evidence to support the routine use of topical PDT for SCC (Rating: CIIiii).
- Superficial Basal Cell Carcinoma (sBBC): PDT is an effective and reliable treatment option for SBCC that offers excellent cosmetic outcomes (Rating: AI); PDT offers an advantage in treatment of large, extensive and multiple lesions (Rating AI); MAL-PDT has demonstrated long-term efficacy, with 5 year follow up data (Rating: AI).
- Nodular Basal Cell Carcinoma (nBBC): MAL-PDT is an effective and reliable treatment option for nBBC less than 2 mm in depth with the advantage of good cosmetic outcome (Rating: AI); MAL-PDT has demonstrated long-term efficacy with 5 year follow up data. (Rating: AI).
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 physicians 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 Altilite 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 necessaryas a treatment of:
- Non-hyperkeratotic actinic keratoses of the face and scalp.
- Low risk superficial or nodular (less than 2 mm in depth) basal cell skin cancer only when surgery and radiation are contraindicated.
- Bowen's disease (squamous cell carcinoma in situ) only when surgery and radiation are contraindicated.
Photodynamic therapy is considered investigational for other dermatologic applications, including, but not limited to the following:
- Acne vulgaris,
- High risk basal cell carcinomas,
- Hidradenitis suppurativa,
No high-quality comparative studies have evaluated photodynamic therapy for acne or other dermatologic 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.
Procedure Codes and Billing Guidelines:
- To report provider services, use appropriate CPT* codes, Modifiers, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or diagnosis codes.
- 96567 photodynamic therapy for actinic keratosis.
- J7308 5-ALA (Levulan® Kerastick®) for topical administration.
- J7309 Methyl aminolevulinate (MAL) for topical administration, 16.8%, 1 gram
- Feldman SR, Fleischer AB, Williford PM, Jorizzo JL. Destructive procedures are the standard of care for the treatment of actinic keratoses. The Journal of American Academy of Dermatology1999;40:43-47
- Leber K, Perron VD, Sinni-McKeehen B. Common Skin Cancers in the United States: A Practical Guide for Diagnosis and Treatment. Nurse Practitioner Forum 1999;10 (2): 106-112
- Jeffes III EWB, Tang EH. Actinic Keratosis. The Journal of Clinical Dermatology2000 May-June;1(3):167-179
- Ormrod D, Jarvis B. Topical Aminolevulinic Acid HCl Photodynamic Therapy. The Journal of Clinical Dermatology2000 March-April;1 (2): 133-139
- Barnaby JWJ, Styles AR, Cockerell CJ. Actinic Keratoses. Drugs and Aging 1997 September;11(3)186-205
- ECRI Institute. Photodynamic Therapy with Aminolevulinic Acid for Treatment of Actinic Keratosis and Other Skin Lesions. Plymouth Meeting (PA): ECRI InstituteExternal Site; 2008 August 6. 17 p. [ECRI hotline response].
- Morton CA, McKenna KE, Rhodes LE; British Association of Dermatologists Therapy Guidelines and Audit Subcommittee and the British Photodermatology Group. Guidelines for topical photodynamic therapy: update. Br J Dermatol. 2008 Dec;159(6):1245-66.
- Orringer JS, Sachs DL, Bailey E et al. Photodynamic therapy for acne vulgaris: a randomized, controlled, split-face clinical trial of topical aminolevulinic acid and pulsed dye laser therapy. J Cosmet Dermatol. 2010 Mar;9(1):28-34.
- Foley P, Freeman M, Menter A et al. Photodynamic therapy with methyl aminolevulinate for primary nodular basal cell carcinoma: results of two randomized studies. Int J Dermatol. 2009 Nov;48(11):1236-45.
- Fantini F, Greco A, Del Giovane C et al. Photodynamic therapy for basal cell carcinoma: clinical and pathological determinants of response. J Eur Acad Dermatol Venereol. 2011 Aug;25(8):896-901. doi: 10.1111/j.146803083.2010.03877.x. Epub 2010 Nov 4.
- Fayter D, Corbett M, Heirs M et al. A systematic review of photodynamic therapy in the treatment of pre-cancerous skin conditions, Barrett’s oesphagus and cancers of the biliary tract, brain, head and neck, lung, oesphagus and skin. Health Technol Assess. 2010 Jul;14(37):1-288.
- Roozeboom MH, Arits AH, Nelemans PJ, Kelleners-Smeets NW. Overall treatment success after treatment of primary superficial basal cell carcinoma: a systematic review and meta-analysis of randomized and non-randomized trials. Br J Dermatol. 2012 May 21. [Epub ahead of print]
- Hadley J, Tristani-Firouzi P, Hull C, Florell S, et al. Results of an investigator-initiated single-blind split-face comparison of photodynamic therapy and 5% imiquimod cream for the treatment of actinic keratoses. Dermatol Surg. 2012 May;38(5):722-7.
- Serra-Guillen C, Nagore E, Hueso L, Traves V, 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. 2012 Apr;66(4):e131-7.
- Medscape Reference Drugs, Diseases and Procedures. Photodynamic Therapy for the Dermatologists. Jaggi Rao, M.D. et al. Updated March 3, 2014.
- National Comprehensive Cancer NetworkExternal Site (NCCN) Version 2.2014 Basal and Squamous Cell Skin Cancers.
- UpToDateExternal Site. Treatment of Actinic Keratosis. Joseph Jorizzo M.D.. Topic last updated June 21, 2013.
- UpToDateExternal Site. Treatment and Prognosis of Basal Cell Carcinoma. Timothy K. Chartier, M.D., Sumaria Z. Aasi, M.D.Topic last updated March 14, 2014.
- UpToDateExternal Site. Treatment and Prognosis of Cutaneous Squamous Cell Carcinoma. Timothy K. Chartier, M.D., Sumaira Z. Aasi, M.D. Topic last updated January 22, 2014.
- UpToDateExternal Site. Nonablative Skin Resurfacing for Skin Rejuvination. Macrene Alexiades-Armenakas, M.D., PhD. Topic last updated January 15, 2013.
- CMSExternal Site National Coverage Determination (NCD) for Treatment of Actinic Keratosis (250.4).
- National Comprehensive Cancer NetworkExternal Site (NCCN) Basal Cell Skin Cancer, Version 1.2016.
- National Comprehensive Cancer NetworkExternal Site (NCCN) Squamous Cell Skin Cancer, Version 1.2016.
- American Academy of DermatologyExternal Site: Actinic Keratosis: Diagnosis, Treatment and Outcome; Basal Cell Carcinoma: Diagnosis, Treatment and Outcome; Hidradenitis Suppurativa: Diagnosis, Treatment and Outcome; Warts: Diagnosis, Treatment and Outcome.
- National Guideline ClearinghouseExternal Site: British Association of Dermatologists’ Guidelines for the Management of Squamous Cell Carcinoma In Situ (Bowen’s Disease) 2014.
- Braathen LR, Szeimies RM, Basset-Seguin N, et. al. 2005 Consensus Based Guidelines on the use of PDT for non-melanoma skin cancer, International Society for Photodynamic Therapy in Dermatology. J Am Acad Dermatol. Jan 2007;56(1):125-143.
- UpToDateExternal Site. Treatment of Actinic Keratosis. Joseph Jorizzo, M.D., Topic last updated January 4, 2016.
- UpToDate. Treatment and Prognosis of Basal Cell Carcinoma, Timothy K. Chartier, M.D., Sumaira Z. Aasi, M.D., Topic last updated December 9, 2015
- UpToDateExternal Site. Treatment and Prognosis of Cutaneous Squamous Cell Carcinoma, Timothy Chartier, M.D., Sumaira Z. Aasi, M.D., Topic last updated December 21, 2015.
- Patel G. Armstrong AW, Eisen DB. Efficacy of Photodynamic Therapy vs Other Interventions in Randomized Clinical Trials for the Treatment of Actinic Keratoses: A Systemic Review and Meta-Analysis. JAMA Dermatol. August 27, 2014
- Zane C, Facchinetti E, Rossi MT, et. al. A randomized clinical trial of photodynamic therapy with methyl aminolaevulinate vs. diclofenac 3% plus hyaluronic acid gel for the treatment of multiple actinic keratosis of the face and scalp. Br J Dermatol. May 2014;170(5):1143-1150
- Bath-Hextall FJ, Perkins W, Bong J, et. al. Interventions for basal cell carcinoma of the skin. Cochrane Database Syst Rev. 2007(1):CD003412
- Wang H, Xu Y, Shi J, et. al. Photodynamic therapy in the treatment of basal cell carcinoma: a systematic review and meta analysis. Photodermatol Photoimmunol Photomed. Nov 5 2014
- Bath-Hextall FJ, Matin RN, Wilkinson D, et. al. Interventions for cutaneous Bowen’s disease. Cochran Database Syst Rev. 2013;6:CD007281
- Lansbury L, Bath-Hextall F, Perkins W, et. al. Interventions for non-metastatic squamous cell carcinoma of the skin: systematic review and pooled analysis of observational studies. BMJ. 2013;347:f6153
- Shaaban D, Abdel-Samad Z, El-Khalawany M. Photodynamic therapy with intralesional 5-aminolevulinic acid and intense pulsed light versus intense pulsed light alone in the treatment of acne vulgaris: a comparative study. Drmatol Ther. Jan-Feb 2012;25(1):86-91
- Morton CA, McKenna KE, Rhodes LE, et. al. Guidelines for topical photodynamic therapy: update. Br J Dermatol. Dec 2008;159(6):1245-1266
- Scheinfeld N. The use of photodynamic therapy to treat hidradenitis suppurativa a review and critical analysis. Dermatol Online J 2015 Jan 15;21(1)
- Kerdel FA. Current and emerging nonsurgical treatment options for hidradenitis suppurativa. Semin Cutan Med Surg. 2014 Jun;33(3 suppl):S57-9
February 2016 - Annual Review, Policy Renewed
March 2015 - Annual Review, Policy Revised
April 2014 - Annual Review, Policy Renewed
May 2013 - Annual Review, Policy Renewed
June 2012 - Annual Review, Policy Renewed
August 2011 - Annual Review, Policy Renewed
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*Current Procedural Terminology © 2012 American Medical Association. All Rights Reserved.