Photodynamic therapy (PDT) involves the use of photochemical reactions mediated through the interaction of photosensitizing agents, light, and oxygen for the treatment of malignant or benign diseases. This policy addresses (1) photodynamic therapy with porfirmer sodium (Photofrin®), (2) photodynamic therapy with topical 5-Aminolevulinic Acid (5-ALA or Levulan® Kerastick™) and exposure to blue light illumination using the BLU-U™ Blue Light Photodynamic Therapy Illuminator for the treatment of actinic keratoses, and (3) ocular photodynamic therapy with verteporfin (Visudyne®).   

Photodynamic Therapy with Porfirmer Sodium (Photofrin®)

Medically Necessary:

Photodynamic therapy with porfirmer sodium (Photofrin®) is considered medically necessary for any of the following:

• Palliation of patients with completely obstructing esophageal cancer, or of patients with partially obstructing esophageal cancer who, in the opinion of their physician, cannot be satisfactorily treated with Nd:YAG laser therapy; or
• Reduction of obstruction and palliation of symptoms in patients with completely or partially obstructing endobronchial non-small cell lung cancer (NSCLC) who are ineligible for surgery; or
• Treatment of microinvasive endobronchial NSCLC in patients for whom surgery and radiotherapy are not indicated; or
• Treatment of Barrett’s esophagus-associated high-grade dysplasia; or
• Treatment of Barrett’s esophagus-associated early stage adenocarcinoma in patients who are not candidates for esophagectomy.
  
  

Investigational/ Not Medically Necessary:

Photodynamic therapy with porfirmer sodium (Photofrin®) is considered investigational/not medically necessary in all other cases, including but not limited to the following:

• Treatment of Barrett’s esophagus-associated low-grade dysplasia;
• Treatment of Barrett’s esophagus-associated early stage squamous cell esophageal cancer;
• Early-stage, bronchoscopically accessible lesions for patients with multiple primary lung cancers;
• Early-stage, microinvasive endobronchial non-small cell lung cancer in patients who are surgical candidates;
• Curative treatment of patients with early superficial cancers of the oral cavity, larynx and oropharynx or as a palliative intraoperative adjuvant treatment for recurrent infiltrating tumors of the head and neck, including the oral cavity, pharynx and larynx.
  
  

Photodynamic Therapy with Topical 5-Aminolevulinic Acid (5-ALA or Levulan®) and Exposure to Blue Light Illumination using the BLU-U^TM Blue Light Photodynamic Therapy Illuminator

Medically Necessary:

Photodynamic therapy with topical 5-Aminolevulinic Acid (5-ALA or Levulan®) and exposure to blue light illumination using the BLU-U^TM Blue Light Photodynamic Therapy Illuminator is considered medically necessary for the treatment of non-hyperkeratotic actinic keratoses of the face or scalp.

Investigational/Not Medically Necessary:

Photodynamic therapy with topical 5-ALA and exposure to blue light illumination using the BLU-U^TM Blue Light Photodynamic Therapy Illuminator is considered investigational/not medically necessary for all other dermatologic applications not identified above as medically necessary.  This includes, but is not limited to, use for the treatment of grade 3 (thick) hyperkeratotic actinic keratoses, or of lesions on the trunk or extremities. 

Note: For the treatment of acne vulgaris, please refer to Medical Policy MED.00063 Treatment of Acne Vulgaris Using Pulsed Dye Laser or Photodynamic Therapy. 

Ocular Photodynamic Therapy with Verteporfin (Visudyne®)

Medically Necessary:

Ocular photodynamic therapy with verteporfin (Visudyne®) is considered medically necessary as a treatment for choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD), or pathologic myopia, or presumed ocular histoplasmosis.

Repeat photodynamic therapy with verteporfin (Visudyne®) for the above indications is considered medically necessary at intervals no more frequently than every three (3) months.

Investigational/Not Medically Necessary:

Ocular photodynamic therapy with verteporfin (Visudyne®) is considered investigational/not medically necessary for all other ophthalmologic disorders not identified above as medically necessary.

Note:  For information about other treatments for age-related macular degeneration, please refer to:

• Policy DRUG.00028 Treatment for Age Related Macular Degeneration; and
• Policy SURG.00070 Photocoagulation of Macular Drusen.

Rationale

Oncologic Indications - Photodynamic Therapy with Porfirmer Sodium (Photofrin®)

Obstructing Esophageal Tumors

When used for palliative treatment, relevant outcomes include short-term resolution of symptoms, such as dysphagia or improvement in swallowing. Long-term outcomes, such as disease-free survival, may not be relevant in the palliative setting. The product insert for Photofrin describes a multi-center, single-arm study of the use of photodynamic therapy in 17 patients with obstructing esophageal cancer (Sanofi Pharmaceuticals product insert).  Patients received from one to three monthly treatments of photodynamic therapy. Of the 17 treated patients, 11 (65%) received clinically important benefit from photodynamic therapy, defined as either complete tumor response/normal swallowing, or improvement in dysphagia. Endoscopic debridement of the esophagus may be required after the photodynamic therapy. At this time, the residual tumor can also be re-treated.

Obstructing Endobronchial Tumors

Similar to obstructing esophageal tumors, short-term outcomes are also relevant for photodynamic therapy as a treatment of endobronchial tumors. At the present time, laser ablation is commonly used to treat endobronchial lesions, and thus, the relative efficacy of photodynamic therapy and laser ablation is also relevant. The product insert cites two studies totaling 211 patients with obstructing endobronchial tumors who were randomized to receive photodynamic therapy or Nd:YAG laser therapy.  The response rates, (i.e., the sum of complete and partial response rates) for the two treatments were similar at one week (59% photodynamic therapy, 58% laser therapy) with a slight increase in response rates for photodynamic therapy at six weeks (60% photodynamic therapy, 41% laser therapy). Clinical improvement, as evidenced by improvements in dyspnea, cough, and hemoptysis, were similar in the two groups at one week (25%–29%); however, at one month or later, 40% of patients treated with photodynamic therapy reported clinical improvement, compared to 27% treated with laser therapy. Due to missing data in the studies, statistical comparisons were not performed.

In another small, published, randomized study comparing photodynamic therapy and Nd:YAG laser therapy in patients with airway obstruction, Diaz-Jimenez and colleagues reported that the two techniques had similar effectiveness over a 24-month period (Diaz-Jimenez, 1999).  The authors noted a better immediate response rate associated with laser therapy and suggested that laser therapy may be particularly appropriate for those requiring rapid relief of symptoms. Results of a larger case series of 100 patients with unresectable lesions also reported that photodynamic therapy is associated with successful palliation (Moghissi, 1999).

Similar to treatment of obstructing esophageal lesions, repeat endoscopy may be required for tumor debridement, at which time repeat photodynamic therapy may be performed to treat residual tumor.

Early Stage Lung Cancer

It is anticipated that only a minimal number of patients with non-obstructing lung cancer will be appropriate candidates for photodynamic therapy. Of the 178,000 new cases of lung cancer annually, only 15% are detected with early-stage lung cancer. Of these, approximately 60% are treated with surgery, and another 25% are treated with radiation therapy. Candidates for photodynamic therapy are limited to those patients who cannot tolerate surgery or radiation therapy, most commonly due to underlying emphysema, other respiratory disease, or prior radiation therapy. In this primary treatment setting, long-term outcomes, such as response rates and disease-free survival, are important. The product insert for Photofrin® also refers to three case series totaling 62 patients with microinvasive lung cancer. The complete tumor response rate, biopsy-proven, at least three months after treatment was 50%; median time to tumor recurrence was more than 2.7 years; median survival was 2.9 years; and disease-specific survival was 4.1 years. In another case series of 95 early-stage lung cancers, the complete response rate was 83.2% (Kato, 1996).

The labeled indication suggests that photodynamic therapy for early-stage lung cancer should be limited to those who are not candidates for either surgery or radiation therapy. However, Cortese and colleagues reported on a case series of 21 patients with early-stage squamous cell cancer of the lung who were offered photodynamic therapy as an alternative to surgery (Cortese, 1997).  Patients were followed up closely with repeat endoscopy and surgical resection if cancer persisted after no more than two courses of photodynamic therapy. A total of nine patients (43%) had a complete response at a mean follow-up of 68 months (range 24–116 months) and thus, were spared surgical treatment.

It should be noted that Nd:YAG laser therapy, electrocautery, and endobronchial brachytherapy are also considered treatment options for early-stage lung cancer. However, unlike obstructing endobronchial lesions, no controlled studies have compared the safety and efficacy of these techniques.

Barrett' Esophagus with High-Grade Dysplasia

The FDA-labeled indication for treatment of high-grade dysplasia is based on a multicenter, partially blinded, study that randomized 199 patients to receive either photofrin® plus omeprazole or omeprazole alone.  Initially, 485 patients with high-grade dysplasia were screened for the trial; 49% were subsequently excluded because high-grade dysplasia was not confirmed on further evaluation. As noted in the package insert, the high patient exclusion rate re-enforces the recommendation by the American College of Gastroenterology that the diagnosis of dyplasia in Barrett’s esophagus be confirmed by an expert gastrointestinal pathologist. Patients randomized to the treatment group received up to three courses of photodynamic therapy separated by 90 days. The primary efficacy endpoint was the complete response rate at any one of the endoscopic assessment time points. Complete response was defined, at a minimum, as ablation of all areas of high-grade dysplasia, but with some areas of low-grade dysplasia. A total of 76.8% of patients in the treatment group achieved a complete response, compared to 38.6% in the control group. At the end of 24 months of follow-up, patients in the treatment group had an 83% chance of being cancer free, compared to a 54% chance in the control group.

Other Indications

Although photodynamic therapy has been investigated for a number of years in the treatment of other cancers, such as bladder and other superficial cancers, a search of the National Cancer Institute’s Physician Data Query database revealed only nine ongoing trials. All were either phase I, phase I/II, or phase II studies; there were no phase III clinical trials.

Photodynamic therapy with topical 5-Aminolevulinic Acid (5-ALA or Levulan®)

The FDA approval for Levulan® Kerastick™ for the treatment of actinic keratoses represents the largest clinical trial.  This data was derived from two similarly designed studies that randomized 243 patients with four to 15 non-hyperkeratotic actinic keratoses to receive Levulan® Kerastick™ plus blue light exposure or a vehicle solution plus blue light exposure (Piacquadio, 2004).  From 63% to 69% of patients in the active treatment group reported complete response at eight weeks, compared to 13-14% in the placebo group.  Patients who were not complete responders after eight weeks had re-treatment of the persistent lesions.  Among these patients, 43% showed a complete response after a second treatment, compared to only 4% in the placebo group.

Jeffes, et al. found that hyperkeratotic actinic keratoses on the trunk and extremities were far less responsive to PDT (38% response rate at eight weeks), and this is supported by other studies.  Also, thick, grade 3 lesions were poorly responsive, probably as a result of impaired penetration of topical ALA through the epidermis of hyperkeratotic actinic keratoses. Therefore, the scientific evidence does not support the use of PDT for grade 3 lesions or lesions of the trunk or extremities (Jeffes, 2001).

Photodynamic therapy with verteporfin (Visudyne®)

Results of a series of pivotal randomized studies, referred to as the TAP studies (Treatment of Age related Macular Degeneration with Photodynamic therapy) have reported positive results.  For example, the two year results reported beneficial outcomes regarding visual acuity and contrast sensitivity, noted after 12 months to be sustained through 24 months (Bressler, 2001).  At the end of two years, 53% of the treatment group, as compared to 38% of the placebo group, had lost fewer than 15 letters.  The average number of applications of verteporfin treatment in the second year was lower than that required during the first year.  In addition to delaying or limiting vision loss for up to two years, verteporfin therapy was associated with a number of other benefits when compared to the placebo group.  The benefits included less progression of classic CNV beyond the area of the lesion baseline, less fluorescein leakage from classic CNV, and fewer lesions greater than six disc areas.  Subgroup analysis was also reported, comparing results between those patients with predominantly classic CNV (> 50% of lesional area) and those with minimally classic CNV (< 50%) with no statistically significant improvements in visual acuity noted for the minimally classic group.  TAP Report No. 7 (Bressler, 2005) documented results of the open-label extension of the TAP investigation at the 48-month mark.  Long-term outcomes between the 24-month and 48-month follow-up for the original study population of patients with predominantly classic CNV found that visual acuity remained stable with no new safety issues identified and no acute visual decreases in acuity amongst the treatment group.

Cochrane performed a meta-analysis of two randomized trials to examine the effects of PDT in the treatment of patients (n = 948) with classic and occult choroidal neovascular AMD.  Verteporfin therapy was compared to a placebo group over a period of 24 months with outcomes measured by loss of lines of visual acuity, contrast sensitivity, central visual field function, neovascular membrane morphology, quality of life and adverse effects.  The analysis indicated that PDT can prevent vision loss and further deterioration in individuals with active neovascular disease but it cannot restore vision loss.  The authors concluded that PDT is probably effective in preventing vision loss for both classic and occult CNV due to AMD; however, the extent of the therapeutic effect remains uncertain (Wormald, 2005).

Photodynamic therapy has also been investigated in patients with CNV related to pathologic myopia and presumed ocular histoplasmosis.  A second arm of the Verteporfin in Photodynamic Therapy (VIP) trial focused on 120 patients with pathologic myopia and CNV, either classic, occult, or mixed (although 90% of those studied had classic CNV), who were randomized to receive photodynamic therapy or placebo.  At month 12, PDT stabilized or improved vision, (as defined by a loss of fewer than 8 letters on a standard eye chart), in 72% of patients vs. 44% on placebo.  The authors concluded that verteporfin therapy increases chances of stabilizing or improving vision compared to placebo for at least one year.  Comparison results for those with predominantly classic CNV vs. occult CNV were not reported (VIP Report No. 1, 2001). 

There are minimal published data regarding use of PDT in patients with CNV related to ocular histoplasmosis.  FDA approval was based on an open-label safety study involving 26 patients with ocular histoplasmosis where visual acuity improved by an average of more than one line on a standard eye chart at 12 months with 28% experiencing an improvement of three lines or more ((CMS, 2004).

Background/Overview

Photodynamic therapy (PDT), a form of phototherapy, refers to a group of treatment types that includes the use of light to induce reactions in the body to treat various diseases. PDT is a technique that can potentially destroy unwanted tissue but spare normal tissue. This therapy has been proven useful for the treatment of various cancers (non-small cell lung cancer and esophageal cancers), as well as for treatment of actinic keratoses and age-related macular degeneration. Generally, PDT begins with the administration of a photosensitizing agent which makes the exposed tissues susceptible to light therapy, while leaving unexposed tissue immune. When light, (often from a laser), is directed at tissue containing the agent, the agent becomes activated, and the tissue is rapidly destroyed.  Tissue not treated with the agent is unaffected. Thus, by careful application of the agent and light beam, the technique can be targeted selectively to treat abnormal tissue.

PDT is appropriate for palliative care for patients with advanced stages of lung cancer who are not candidates for alternative interventions. Since most patients with lung cancer initially present with advanced disease, survival rates are low, and current standard treatments are rarely palliative. According to the American Cancer Society, lung cancer is the most common cause of cancer related death in the United States. Non-small cell lung cancer (NSCLC) accounts for 75% of all lung cancer cases. It is specifically for this subgroup of lung cancer patients that PDT has been most beneficial. Surgery and radiotherapy are alternative treatments of lung cancer, though these interventions are most effective in the treatment of early stages of lung cancer. Similar to its use in lung cancer, PDT is appropriate for palliative care of advanced esophageal cancer, as well as for advanced cases of a pre-cancerous condition called Barrett’s esophagus. Esophageal cancer frequently arises from untreated Barrett’s esophagus. Barrett’s esophagus occurs as a result of chronic gastroesophageal acid reflux (GERD), a condition that affects approximately 20% of the adult population in the United States.

Porfirmer sodium, also known as Photofrin,® is the most extensively studied photosensitizing agent to date. This drug tends to accumulate more in cancerous tissue than normal tissue. Photofrin® is usually injected intravenously, so that the agent is circulated in the blood stream and absorbed by all cells in the body. While the agent rapidly leaves normal cells in a few hours, it is commonly retained for several days in tumor cells. Timing of this procedure is very important; as it should be performed when most of the drug has left the healthy cells but remains in the tumor cells.

PDT is appropriate for the treatment of actinic keratoses, pre-cancerous skin lesions that are commonly associated with long-term exposure to the sun. Typically, the lesions are confined to the outer layer (epidermis) of the skin. However, in up to 20% of all cases, actinic keratoses are the precursor to skin cancer. For this reason, actinic keratoses are known as the most common precancerous lesion in the United States. Actinic keratoses have the potential to change into squamous cell carcinomas, which according to the American Cancer Society, is the second most common type of skin cancer in the United States. Between 80,000 and 100,000 new cases are reported annually. For the treatment of actinic keratoses, 5-aminolevulinic acid (ALA or Levulan®) is used as a photosensitizing agent and is applied directly to the surface of the skin. ALA is not absorbed selectively by actinic keratoses, so photosensitization of normal tissues may result. Following treatment, actinic keratoses lesions form into dry scaly skin or crusts, which then heal naturally. Standard methods for treatment of actinic keratoses include cryotherapy (freezing) and chemodestruction (burning). These methods aim to destroy the lesion, but often result in damage to the surrounding skin.

Age-related macular degeneration (AMD) is an eye disease caused by destruction of the central area in the retina, the light-sensitive layer of nerve cells lining the back of the eye. AMD is the leading cause of severe and irreversible vision loss in the developed world among people over the age of 60. In the “wet” form of macular degeneration, new blood vessels grow across the back of the eye, a process called choroidal neovascularization. These blood vessels often leak blood and serum, which causes interference with central vision, (necessary for reading and driving activities). Two additional eye conditions have also been shown to benefit from PDT - pathologic myopia, (which is caused by continuation of eyeball growth past the normal timeframe) and ocular histoplasmosis, an infection where the fungus Histoplasma capsulatum is believed to grow in the tissues at the back of the eye causing small areas of inflammation and scarring of the retina. For the treatment of “wet” macular degeneration, pathologic myopia or presumed ocular histoplasmosis, the photosensitizing agent used is verteporfin, (Visudyne®).  Currently, there is no cure for any of these conditions, and while PDT cannot return vision, it can halt the further deterioration of vision loss.

Definitions

Actinic keratoses: a small rough area of skin chronically exposed to the sun, which may develop into skin cancer.

Adenocarcinoma: a cancer that develops in the lining or inner surface of an organ.

Barrett’s esophagus: a complication due to chronic severe gastrointestinal reflux disease (GERD), where the cells that line the esophagus near the stomach become pre-cancerous; there is a small but definite increased risk of cancer of the esophagus (adenocarcinoma) in people with Barrett’s esophagus.

Choroidal neovascularization: a condition characterized by the development of new blood vessels across the back portion of the eye, which may interfere with vision.

Dysplasia: an abnormality in development, size, shape, or organization of cells.

Macular degeneration: a disease that progressively destroys the macula, which is the central portion of the retina, impairing the ability to see straight ahead; macular degeneration rarely causes total blindness, because only the center of vision is affected.

Non-small cell lung cancer (NSCLC): a type of cancer of the lung originating in the lining of the lung air passages.

Palliation: treating the symptoms of a disease, such as pain or other discomfort, designed to palliate or make the patient more comfortable but not intended to cure the disease itself.

Squamous cell: thin, flat cells that look like fish scales under the microscope; squamous cells cover external and certain internal surfaces of the body.

Stage: a measure of the extent of a cancer, especially whether the disease has spread from the original site to other parts of the body.

Coding

The following codes for treatments and procedures applicable to this policy are included below for informational purposes.  Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy.  Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

Photodynamic therapy with porfirmer sodium for oncologic applications
When services are Medically Necessary:

CPT

HCPCS

ICD-9 Diagnosis

When services may be Medically Necessary when criteria are met:

For the procedure codes listed above for the following diagnosis.

ICD-9 Diagnosis

When services are Investigational/Not Medically Necessary:

For the procedure codes listed above, for all other diagnoses not listed, when criteria are not met; or when the code describes a procedure indicated in the Policy section as investigational/not medically necessary.

Photodynamic therapy with topical 5-Aminolevulinic Acid (5-ALA or Levulan®)
When services are Medically Necessary:

CPT

HCPCS

ICD-9 Diagnosis

When services are Investigational/Not Medically Necessary:

For the procedure codes listed above, for all other diagnoses not listed; or when the code describes a procedure indicated in the Policy section as investigational/not medically necessary.

Ocular photodynamic therapy with verteporfin (Visudyne®)
When services are Medically Necessary:

CPT

HCPCS

ICD-9 Diagnosis

When services are Investigational/Not Medically Necessary:

For the procedure codes listed above, for all other diagnoses not listed; or when the code describes a procedure indicated in the Policy section as investigational/not medically necessary.

References

Peer Reviewed Publications:

1. Bressler NM.  Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin:  two-year results of 2 randomized clinical trials.  TAP Study Group.  Arch Ophthalmol. 2001; 119(2):198-207.
2. Bressler NM, Bressler SB, Haynes LA, et al. Verteporfin therapy for subfoveal choroidal neovascularization in age-related macular degeneration:  four-year results of an open-label extension of 2 randomized clinical trials:  TAP Report No. 7.  Arch Ophthalmol. 2005; 123(9):1283-85.
3. Bressler SV, Pieramici DJ, Koester JM, et al. Natural history of minimally classic subfoveal choroidal neovascular lesions in the treatment of age-related macular degeneration with photodynamic therapy (TAP) investigation: outcomes potentially relevant to management.  TAP Report No. 6.  Arch Ophthalmol. 2004; 122(3):325-9.
4. Bressler NM, Arnold J, Benchaboune MS, et al. Verteporfin therapy of subfoveal choroidal neovascularization in patients with age-related macular degeneration: additional information regarding baseline lesion composition’s impact on vision outcomes.  TAP Report No. 3.  Arch Ophthalmol. 2002; 120(11):1443-54.
5. Cortese DA, Edell ES, Kinsey JH. Photodynamic therapy for early stage squamous cell carcinoma of the lung. Mayo Clin Proc. 1997; 72(7):595-602. 
6. Diaz-Jimenez JP, Martinez-Ballarin JE , Llunell A, et al. Efficacy and safety of photodynamic therapy versus Nd-YAG laser resection in NSCLC with airway obstruction. Eur Respir J. 1999; 14(4):800-5.
7. Jeffes EW, McCullough JL, Weinstein GD, et al. Photodynamic therapy of actinic keratoses with topical aminolevulinic acid and fluorescent blue light. J Am Acad Dermatol. 2001; 45(1):96-104.
8. Kato H, Okunaka T, Shimatani H. Photodynamic therapy for early stage bronchogenic carcinoma. J Clin Laser Med Surg. 1996; 14(5):235-8.
9. Moghissi K, Dixon K, Stringer M, et al. The place of bronchoscopic photodynamic therapy in advanced unresectable lung cancer: experience of 100 cases. Eur J Cardiothorac Surg. 1999; 15(1):1-6.
10. Piacquadio DJ, Chen DM, Farber HF, et al. Photodynamic therapy with aminolevulinic acid topical solution and visible blue light in the treatment of multiple actinic keratoses of the face and scalp: investigator-blinded, phase 3 multicenter trials.  Arch Dermatol. 2004; 140(1):41-6.
11. Verteporfin in Photodynamic Therapy (VIP) Study Group.  Photodynamic therapy of subfoveal choroidal neovascularization in pathologic myopia with verteporfin.  1-year results of a randomized clinical trial.  VIP Report No. 1.  Ophthalmol. 2001; 108(5):841-52.
12. Verteporfin in Photodynamic Therapy (VIP) Study Group.  Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration:  two-year results of a randomized clinical trial including lesions with occult with no classic choroidal neovascularization.  VIP Report No. 2.  Am J Ophthalmol. 2001; 131(5):541-60.
13. Wormald R, Evans J, Smeeth L, et al.  Photodynamic therapy for neovascular age-related macular degeneration.  Cochrane Database Syst Rev. No. CD002030.  October 19, 2005. 

Government Agency, Medical Society, and Other Authoritative Publications:

1. American Academy of Ophthalmology. Preferred Practice Patterns in Age Related Macular Degeneration. Available at: www.aao.org/aao/education/library/ppp/index.cfm. Accessed on: July 17, 2006.
2. American Academy of Dermatology (AAD). Actinic keratoses: new treatment options for this advanced warning sign of skin cancer.  2001 Oct. Available at: http://www.aad.org. Accessed on: July 17, 2006.
3. American Society for Dermatologic Surgery.  Technology report.  Topical photodynamic therapy.  May 2005.  Available at: http://www.asds-net.org.  Accessed on:  July 17, 2006.
4. Blue Cross Blue Shield Association. TEC Special Report: current and evolving strategies in the treatment of age-related macular degeneration.  Technology Evaluation Center.  October 2005.
5. Centers for Medicare and Medicaid Services. National Coverage Determination: Ocular Photodynamic Therapy (OPT). NCD #80.2. Effective April 1, 2004. Available at: http://www.cms.hhs.gov. Accessed on: July 17, 2006.
6. Centers for Medicare and Medicaid Services. National Coverage Determination: Treatment of Actinic Keratosis (AKs).  NCD #250.4. Effective: November 26, 2001. Available at: http://www.cms.hhs.gov. Accessed on: July 17, 2006.
7. Centers for Medicare and Medicaid Services. National Coverage Determination: Verteporfin. NCD #80.3. Effective: April 1, 2004. Available at: http://www.cms.hhs.gov. Accessed on: July 17, 2006.
8. Hayes, Inc. Hayes Medical Technology Directory.  Photodynamic therapy for Barrett’s esophagus and esophageal cancer. Lansdale, PA: Hayes, Inc; April 30, 1999. Search updated: February 6, 2002. 
9. Hayes, Inc. Hayes Medical Technology Directory. Photodynamic therapy for actinic keratoses.  Lansdale, PA: Hayes, Inc; May 9, 2001.  Search updated May 23, 2004.  
10. Hayes, Inc. Hayes Medical Technology Directory.  Photodynamic therapy with verteporfin (Visudyne) for neovascular age related macular degeneration. Lansdale, PA: Hayes, Inc; August 17, 2000.  Search updated: May 2002.  
11. National Institute for Clinical Excellence (NICE).  Interventional procedures overview of photodynamic therapy for non-melanoma skin tumours (including premalignant and primary, non-metastatic skin lesions).  April 2005.  Available at:  http://www.nice.org.uk/pdf/.  Accessed on:  July 17, 2006.
12. National Institute of Clinical Excellence (NICE).  Technology appraisal guidance 68: Photodynamic therapy for age-related macular degeneration.  September 2003.  Available at:  http://www.nice.org.uk/pdf/68_PDT_summary.pdf.  Accessed on:  July 17, 2006.
13. National Institute of Clinical Excellence (NICE).  Interventional procedure guidance: Photodynamic therapy for high-grade dysplasia in Barrett’s esophagus. August 2004.  Available at:  http://www.nice.org.uk/pdf/ip/IPG082guidance.pdf.  Accessed on:  July 17, 2006.
14. Society for Surgery of the Alimentary Tract (SSAT).  SSAT patient care guidelines: Management of Barrett’s esophagus.  October, 2000.  Available at:  http://www.ssat.com/cgi-bin/barretts.cgi?printme=1&affiliation=other&referer=.  Accessed on:  July 17, 2006.
15. U.S. Food and Drug Administration (FDA).  Labeling and Operating Manual: Levulan Kerastick (DUSA Pharmaceuticals, Inc.).  Available at: http://www.fda.gov/cdrh/pdf/P990019c.pdf  Accessed on: July 17, 2006.
16. U.S. Food and Drug Administration (FDA). Summary of safety and effectiveness.  BLU-U Blue Light Photodynamic Therapy Illuminator (DUSA Pharmaceuticals, Inc.). Dec. 3, 1999. Available at:  http://www.fda.gov/cdrh/pdf/P990019b.pdf.  Accessed on:  July 17, 2006.
17. U.S. Food and Drug Administration (FDA).  Visudyne final print label.  April 2000.  Available at: http://www.fda.gov/.  Accessed on:  July 17, 2006.
18. U.S. Food and Drug Administration (FDA).  Center for Devices and Radiological Health (CDRH).  Photofrin for treatment of precancerous lesions in Barrett’s esophagus.  Premarket approval decisions.  August 2003.  Available at:  http://www.fda.gov/bbs/topics/ANSWERS/2003/ANS01246.html.  Accessed on:  July 17, 2006. 

1. American Academy of Dermatology (AAD). ActinicKeratosesNet. Treatment options.  AAD 2005.  Available at: http://www.skincarephysicians.com/actinickeratosesnet/treatmentoptions.html.  Accessed on:  July 17, 2006.
2. DUSA® Pharmaceuticals, Inc.  Levulan® Kerastick™ product insert.  ©2004 DUSA Pharmaceuticals, Inc., Wilmington, MA.  Available at: http://www.dusapharma.com/products_levulan_brochures.html#  Accessed on: July 17, 2006.
3. Product insert, Photofrin® (Sanofi-Aventis Pharmaceuticals).  Available at: www.sanofi-synthelabous.com.  Accessed on:  July 17, 2006.
4. American Cancer Institute (NCI).  Esophageal cancer.  Available at:  http://www.cancer.gov/cancertopics/types/esophageal.  Accessed on:  July 17, 2006.
5. National Comprehensive Cancer practice guidelines.  Available at: www.nccn.org.  Accessed on:  July 17, 2006.

Index

5-ALA (5-Aminolevulinic Acid)
BLU-U™ Blue Light Photodynamic Therapy Illuminator
Levulan® Kerastick™ for Actinic Keratoses
Macular Degeneration, Photodynamic Therapy for
Photodynamic Therapy - Eye
Photodynamic Therapy for the Treatment of Actinic Keratoses
Photofrin® Porfirmer Sodium
Skin Lesions, Photodynamic Therapy for
Solar Keratoses, Photodynamic Therapy for the Treatment of
Verteporfin
Visudyne^TM

Policy History

Federal and State law, as well as contract language, including definitions and specific contract provisions/exclusions, take precedence over Medical Policy and must be considered first in determining eligibility for coverage. The member's contract benefits in effect on the date that services are rendered must be used. Medical Policy, which addresses medical efficacy, should be considered before utilizing medical opinion in adjudication. Medical technology is constantly evolving, and we reserve the right to review and update Medical Policy periodically.

No part of this publication may be reproduced, stored in a retrieval system or transmitted, in any form or by any means, electronic, mechanical, photocopying, or otherwise, without permission from the health plan.

©CPT Only - American Medical Association