Medical Policy: 02.01.16
Original Effective Date: January 2002
Reviewed: February 2017
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) 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
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.
Practice Guidelines and Position Statements
National Comprehensive Cancer Network (NCCN)
Version 1.2017 Basal Cell Skin Cancer
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, therapies such as topical 5-fluorouracil, topical imiquimod, photodynamic therapy (e.g. aminolevulinic acid (ALA), porfimer sodium) or vigorous cryotherapy may be considered,even thought the cure rates may be lower than with surgical treatment modalities.
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).
Version 1.2017 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 topical 5-flurouracil, topical imiquimod, photodynamic therapy (e.g. aminolevulinic acid (ALA), profimer sodium) or vigorous cryotherapy may be considered even though cure rates may be lower than the surgical treatment modalities.
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.
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 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:
- 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. 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.
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 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 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
- 96574 Debridement of premalignant hyperkeratotic lesion(s) (ie, 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
- J7308 5-ALA (Levulan® Kerastick®) for topical administration.
- J7309 Methyl aminolevulinate (MAL) for topical administration, 16.8%, 1 gram
- J7345 Aminolevulinic acid HCl for topical administration, 10% gel, 10 mg
- 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): 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 Network (NCCN) Version 2.2014 Basal and Squamous Cell Skin Cancers.
- UpToDate Treatment of Actinic Keratosis. Joseph Jorizzo M.D.. Topic last updated December 12, 2016.
- UpToDate Treatment and Prognosis of Basal Cell Carcinoma at Low Risk of Recurrence. Timothy K. Chartier, M.D., Sumaria Z. Aasi, M.D.Topic last updated December 9, 2015.
- UpToDate. Treatment and Prognosis of Cutaneous Squamous Cell Carcinoma. Timothy K. Chartier, M.D., Sumaira Z. Aasi, M.D. Topic last updated December 21, 2015.
- UpToDate Nonablative Skin Resurfacing for Skin Rejuvination. Macrene Alexiades-Armenakas, M.D., PhD. Topic last updated January 15, 2013.
- CMS National Coverage Determination (NCD) for Treatment of Actinic Keratosis (250.4).
- National Comprehensive Cancer Network (NCCN) Basal Cell Skin Cancer, Version 1.2017.
- National Comprehensive Cancer Network (NCCN) Squamous Cell Skin Cancer, Version 1.2017.
- American Academy of Dermatology 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 Clearinghouse 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.
- 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, 2014:150(12):1281-1288. PMID 2516281
- 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. PMID 24506666
- Bath-Hextall FJ, Perkins W, Bong J, et. al. Interventions for basal cell carcinoma of the skin. Cochrane Database Syst Rev. 2007(1):CD003412. PMID 23794286
- 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. Jan 2015;31(1):44-53. PMID 25377432
- 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. PMID 24191270
- 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
- Roozeboom MH, Artis 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. PMID 27113429
- Zloty D, Guenther LC, Sapijaszko M, et. al. Non-melanoma skin cancer in Canada. Chapter 4: Management of basal cell carcinoma. J Cutan Med Surg. May-Jun 2015;19(3):239-248. PMID 25986316
- Poulin Y, Lynde CW, Barber K, et. al. Non-melanoma skin cancer in Canada. Chapter 3: Management of actinic keratosis. J Cutan Med Surg. May-Jun 2015;19(3):227-238. PMID 25926621
- February 2017 - Annual Review, Policy Renewed
- 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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