BlueCross and BlueShield of Montana Medical Policy/Codes
Photodynamic Therapy (PDT) for the Treatment of Actinic Keratoses (AK) and Other Skin Lesions
Chapter: Therapies
Current Effective Date: September 24, 2013
Original Effective Date: May 09, 2008
Publish Date: September 24, 2013
Revised Dates: March 1, 2010, March 21, 2012; May 2, 2012; July 11, 2013
Description

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.

Two common photosensitizing agents are 5-aminolevulinic acid (5-ALA) and its methyl ester methyl aminolevulinate (MAL). When applied topically, they 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. Photodynamic therapy (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 (BCC). Potential cosmetic indications include skin rejuvenation and hair removal.

Actinic keratoses are rough, scaly, or warty premalignant growths on sun-exposed skin that are very common in older individuals with fair complexions, with a prevalence of greater than 80% in fair-skinned people older than 60 years of age. In some cases, actinic keratosis 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 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 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-fluorouracil, imiquimod, and cryotherapy. Poor cosmesis resulting from surgical procedures and skin irritation induced by topical agents can be significant problems.

Regulatory Status

In 1999, Levulan® Kerastick™, a topical preparation of ALA, in conjunction with illumination with the BLU-U™ Blue Light Photodynamic Therapy Illuminator, received approval by the U.S. Food and Drug Administration (FDA) for the following indication: “The Levulan Kerastick for topical solution plus blue light illumination using the BLU-U Blue Light Photodynamic Therapy Illuminator is indicated for the treatment of non-hyperkeratotic actinic keratoses of the face and scalp.” The product is applied in the physician’s office. As of December 2011, the FDA has not approved this product for use in treating actinic keratoses in locations other than the face and neck.

A 5-aminolevulinic 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.

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 methyl aminolevulinate (MAL) in contrast to ALA used in the Kerastick procedure, followed by exposure with the Aktilite CL 128 lamp, a red light source (in contrast to the blue light source in the Kerastick procedure). Broadband light sources (containing the appropriate wavelengths), intense pulsed light (IPL), pulsed dye lasers (PDL), and potassium titanyl phosphate (KTP) lasers have also been used. Metvixia is indicated for the treatment of non-hyperkeratotic actinic keratoses of the face and scalp in immunocompetent patients when used in conjunction with lesion preparation (debridement using a sharp dermal curette) in the physician's office when other therapies are unacceptable or considered medically less appropriate.

PhotoCure also sought FDA approval of Metvixia for the treatment of BCCs. However, the indication for BCCs was not approved. In April 2009, HealthCanada approved Metvix (as it is called in Canada) for treatment of BCCs, as well as actinic keratoses. Metvixia is also marketed in Europe. 

Policy

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions.  Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusion or other benefit limitations applicable to this service or supply.  If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Medically Necessary

Blue Cross and Blue Shield of Montana (BCBSMT) may consider photodynamic therapy (PDT) medically necessary as a treatment of:

  • Non-hyperkeratotic actinic keratoses (AK) of the face and scalp;
  • Superficial basal cell skin cancer, only when surgery and radiation are contraindicated;
  • Bowen’s disease [squamous cell carcinoma (SCC) in situ], only when surgery and radiation are contraindicated.

Not Medically Necessary 

BCBSMT considers photodynamic therapy as a technique of skin rejuvenation, hair removal, or other cosmetic indications not medically necessary.

Investigational

BCBSMT considers photodynamic therapy experimental, investigational and unproven for other dermatologic applications, including, but not limited to, acne vulgaris, non-superficial basal cell carcinomas, hidradenitis suppurativa, or mycoses.

Rationale

Actinic Keratoses

Multiple randomized controlled trials (RCTs) evaluating photodynamic therapy (PDT) for actinic keratoses have been published. Piacquadio and colleagues published findings in 2004 of data submitted for U.S. Food and Drug Administration (FDA) approval of Levulan® Kerastick™. Two similarly designed studies randomly assigned 243 patients with 4 to 15 non-hyperkeratotic actinic keratoses on the face or scalp to receive active or placebo PDT. From 63% to 69% of patients in the active treatment group reported complete response at 8 weeks, compared to 13% to 14% in the placebo group. Patients who were not complete responders after 8 weeks had retreatment of the persistent lesions. Among these patients, 43% showed a complete response after a second treatment, compared to only 4% in the placebo group. This clinical trial has since been published in the peer-reviewed literature. (1) In a 2003 trial, Pariser and colleagues conducted a randomized, placebo-controlled trial of 80 patients with actinic keratoses. (2) The authors reported that the complete response rate for the methyl aminolevulinate (MAL) group was 89% compared to 38% in the placebo group.

A 2009 double-blind RCT conducted in Germany by Hauschild and colleagues evaluated PDT with 5-aminolevulinic acid (5-ALA) using a self-adhesive patch. (3) Eligibility criteria included Caucasian patients, age 18 years and older with skin type I-IV and actinic keratoses on the head and of mild or moderate grade, as defined by Cockerell (maximum diameter of 1.8 cm and interlesional distance of at least 1 cm). Women of child-bearing potential were excluded, as were individuals who had used treatments or had other conditions that might interfere with study treatments. Patients were randomly assigned to receive 5-ALA patches containing 8 mg 5-ALA or identical placebo patches. Patches were square, measuring 4 cm2, and patients received 3–8 of them, depending on their number of study lesions. The primary efficacy outcome was the complete clinical clearance rate 12 weeks after PDT. A total of 99 of 103 randomized patients were included in the primary efficacy analysis; 4 patients who withdrew from the study were excluded. The complete clinical clearance rate on a per patient basis (all lesions cleared) was 62% (41 of 66) in the 5-ALA patch group and 6% (2 of 33) in the placebo patch group, a statistically significant difference favoring PDT.

Several trials have compared PDT to cryotherapy for treating actinic keratoses. In 2006, Morton and colleagues published an industry-sponsored, 25-center randomized left-right comparison of single photodynamic treatment and cryotherapy in 119 subjects with actinic keratoses on their faces or scalps. (4) At a 12-week follow-up, PDT resulted in a significantly larger rate of cured lesions compared with cryotherapy (86.9% vs. 76.2%, respectively, cured). Lesions with a non-complete response were retreated after 12 weeks; a total of 108 of 725 lesions (14.9%) received a second PDT session; 191 of 714 lesions (26.8%) required a second cryotherapy treatment. At 24 weeks, the groups showed equivalent clearance (85.8% vs. 82.5%, respectively). Thus, approximately 12% more cryotherapy sessions were required to achieve comparable outcomes to PDT. Skin discomfort was reported to be greater with PDT than with cryotherapy. Investigator-rated cosmetic outcomes showed no difference in the percentage of subjects with poor cosmetic outcomes (0.3% vs. 0.5%, respectively), with more subjects rated as having excellent outcomes at 24 weeks after PDT (77.2% vs. 49.7%, respectively). With PDT, 22.5% had cosmetic ratings of fair or good compared to 49.9% for cryotherapy. Subjects perceived PDT to have better efficacy and cosmetic outcome.

In 2010, Szeimies and colleagues in Germany reported 12-month follow-up data from a study comparing PDT using a self-adhesive patch to cryotherapy. (5) The study had the same eligibility criteria and primary outcome as the Hauschild et al. study, (3) described above. A total of 148 patients were randomly assigned to the 5-ALA patch group, 49 to a placebo group, and 149 to a cryotherapy group. The study used a test of non-inferiority of PDT versus cryosurgery. Fourteen patients who dropped out were excluded from the analysis comparing PDT and cryotherapy, leaving 283 patients. The rate of complete clearance of all lesions was 67% (86 of 129) in the 5-ALA group, 52% (66 of 126) in the cryosurgery group, and 12% (5 of 43) in the placebo group. The clearance rate was significantly higher in the 5-ALA patch group than either the cryosurgery group or placebo patch group. Results were similar in the analysis of clearance rates on a lesion basis. The 360 patients with at least 1 lesion cleared at 12 weeks were followed up for an additional 9 months; 316 completed the final visit 1 year after treatment. The overall clearance rate on a lesion basis was still statistically higher in the 5-ALA patch group compared to placebo (in both studies) and compared to cryosurgery (in the second study). Thirty-two percent of patients in the 5-ALA group from the first study and 50% of patients in the 5-ALA group from the second study were still completely free from lesions. The corresponding figure in the cryosurgery group was 37%. Cosmetic outcome was rated by a blinded investigator at each 3-month visit and categorized as excellent, good, fair, or poor. At 1 year, on a per lesion basis, 210 (53%) in the cryosurgery group, 422 (82%) in the 5-ALA patch group, and 47 (90%) in the placebo patch group were categorized as having an excellent cosmetic appearance by the Investigators (statistically better cosmetic appearance in the cryosurgery versus the 5-ALA groups). In addition, 1 year after treatment, 94% of the lesions in the 5-ALA group and only 68% of the lesions in the cryosurgery group were normally pigmented; this difference was statistically significant. In the safety analysis, there were high rates of local reaction to patch application and cryotherapy at the time of treatment, but no serious adverse effects due to study intervention were documented. The photodynamic therapy patches used in the German studies have not been cleared by the FDA for use in the United States.

Basal Cell Carcinoma (BCC)

A 2007 Cochrane review evaluated surgical, destructive (including PDT), and chemical interventions for BCC. (6) The authors concluded that surgery and radiotherapy appeared to be the most effective treatments, with the best results being obtained with surgery. In addition, they stated that cosmetic outcomes appear to be good with PDT, but additional data with long term follow-up are needed. The Cochrane review did not distinguish between BCC subtypes.

Superficial BCC

A 2008 industry-sponsored multicenter open trial compared MAL-PDT with surgery for small (8–20 mm) superficial BCC in 196 patients. (7) At 3 months after treatment, 92% of lesions treated with MAL-PDT showed clinical response, compared with 99% of lesions treated with surgery (per protocol analysis). At a 12-month follow-up, no lesions had recurred in the surgery group, and 9% of lesions had recurred with MAL-PDT. Approximately 10% of patients discontinued MAL-PDT due to an incomplete response or adverse event, as compared with 5% of patients in the surgery group. Cosmetic outcomes were rated by the investigators as good to excellent in 94% of lesions treated with MAL-PDT in comparison with 60% following surgery.

An RCT that compared PDT with cryotherapy for superficial BCC was published in 2008. (8) This multicenter European study included 120 patients, aged 18 and older, with previously untreated primary superficial BCC. Sixty patients with 114 lesions were randomly assigned to treatment with MAL-PDT (1 treatment), and 58 patients with 105 lesions were randomly assigned to cryotherapy (2 freeze-thaw cycles). Patients who had not responded at 3 months received 2 further MAL-PDT sessions (n=20) or repeat cryotherapy (n=16). The primary outcomes were measured 3 months after the last treatment and included 58 patients with 103 lesions in the MAL-PDT group and 57 patients with 98 lesions in the cryotherapy group. The overall response 3 months after the last treatment on a per lesion basis was 100 of 103 (97%) in the MAL-PDT group and 93 of 98 (94.9%) in the cryotherapy group; the difference was not statistically significant. Results were not reported on a per patient basis. Findings were similar for lesions treated once or repeatedly. Treatment groups did not differ in the recurrence rates at any time during follow-up; at 5 years, the overall lesion recurrence rate was 22% with MAL-PDT and 20% with cryotherapy. There was, however, a better cosmetic outcome with MAL-PDT. The percent of lesions rated by investigators as having an excellent cosmetic appearance at 3 months was 30% in the MAL-PDT group and 4% in the cryotherapy group (p=0.0005), and at 5 years was 60% in the MAL-PDT group and 16% in the cryotherapy group (p=0.00078). There was a high rate of local, transitory adverse events, mainly pain; no patients discontinued the study due to treatment-related adverse events. This study did not compare cryotherapy to standard surgical or radiation therapy.

Nodular BCC

Several trials have compared PDT to surgery for treating nodular BCC. In 2008, Mosterd and colleagues published an RCT evaluating 5-ALA PDT for patients with nodular BCC. (9) The study included 149 patients with 173 primary nodular BCC; 85 tumors were assigned to PDT and 88 to surgical excision. Two patients, each with 1 tumor, dropped out before treatment. At 3 months, 78 of 83 (94%) tumors in the 5-ALA-PDT group and 86 of 88 (98%) tumors in the surgery group had resolved completely; this difference was not statistically different. After a median follow-up of 28 months, there were 21 failures (recurrent tumor) after PDT and 2 after surgical excision. A Kaplan-Meier survival analysis estimated the 3-year cumulative incidence of failure as 30.3% in the PDT group and 2.3% in the surgery group (p<0.001).

In 2007, Rhodes et al. published a 5-year follow-up of an industry-sponsored multicenter randomized study comparing MAL-PDT to surgery for nodular BCC. (10,11) A total of 101 adults with previously untreated nodular BCC were randomized to receive MAL therapy or surgery. At 3 months, complete response (CR) rates did not differ between the 2 groups; however, at 12 months, the CR rate had fallen from 91% to 83%, while in the surgery group the CR rate had fallen from 98% to 96%. Of 97 patients in the per protocol population, 66 (68%) were available for 5-year follow-up; 16 (32%) discontinued in the MAL-PDT group due to treatment failure or adverse events versus 6 (13%) in the surgery group. A time-to-event analysis of lesion response over time estimated a sustained lesion response rate of 76% for MAL-PDT and 96% for excision surgery. Cosmetic outcomes were rated as good to excellent in 87% of the MAL-PDT patients and 54% of the surgery patients. Thus, although cosmetic outcomes may be improved, PDT does not seem to be as effective as surgery in terms of the more important clinical outcomes of treatment completion and lesion recurrence.

In 2010, Foley and colleagues reported on a pair of industry-sponsored single-blind RCTs evaluating MAL-PDT versus placebo for treating primary nodular BCC (5 mm or less in depth). (12) One study was conducted in Australia and the other in the United States, but used the same design and procedures. Patients were randomly assigned to receive treatment with PDT using MAL 160 mg/g or placebo cream. The initial treatment cycle consisted of 2 PDT sessions a week apart. Patients whose lesions showed a partial response at the 3-month follow-up underwent a second treatment cycle. Clinical response was categorized as complete response ([CR] disappearance of lesion), partial response ([PR] at least 50% reduction in the longest diameter of the lesion), no response (less than 50% reduction in the longest diameter) or progression (at least 20% increase in the longest diameter). Combining the 2 studies, 131 patients with 160 lesions were enrolled (there were 66 patients in the Australian study and 65 patients in the U.S. study). Sixty-six patients were assigned to the MAL-PDT group and 65 to the placebo group. After randomization, 10 lesions were excluded because they were found histologically not to be nodular BCCs, leaving 150 lesions (75 per group). A total of 117 of 150 lesions (78%) received 1 complete treatment cycle, and 31 of 150 (21%) received 2 complete treatment cycles. The remaining 2 lesions received only a partial treatment cycle. Data on the primary outcome, rate of CR per lesion 6 months after the last treatment is as follows: (Note that p-values were not reported for any of the outcomes).  

MAL-PDT 

Placebo

Overall response 

55/75 (73%)

20/75 (27%)

Response by baseline depth (mm)

 

 

<0.7

14/16 (88%)

5/16 (31%)

0.7 to <1.0

12/15 (80%)

4/15 (27%)

1.0 to <2.0

18/31 (58%)

7/31 (23%)

2.0 to 5.0

9/11 (82%)

4/12 (33%)

Response by baseline diameter (mm)

 

 

<10 mm

49/64 (77%)

18/61 (30%)

10-20 mm

6/11 (55%)

2/14 (14%)

There were small numbers of lesions in some of the stratified analyses, so estimates of response rates are less precise. The rate of any local adverse event was 49 of 66 (74%) in the MAL-PDT group and 30 of 65 (46%) in the placebo group. The most common local event was a burning sensation of the skin, which was reported by 19 patients (29%) in the MAL-PDT group and 8 patients (12%) in the treatment group. In addition, 9 serious adverse events were reported by 6 patients, 2 treated with MAL-PDT and 4 treated with placebo. None of the serious adverse effects were determined to be related to the study treatment. The study is limited by a lack of statistical reporting and a comparison only to placebo, not surgery.

In 2011, Lindberg-Larsen et al. published an uncontrolled retrospective study evaluating recurrence of BCC after treatment with PDT. (13) A total of 90 patients with 157 lesions (n=111 superficial BCC, n=40 nodular BCC and n=6 unknown) were initially treated with MAL-PDT. Each lesion was treated twice, with 1 week between treatments. The authors did not report the initial rate of clinical response. Recurrence was defined as reappearance of a histologically-verified BCC in a previously affected area. The estimated recurrence rate was 11% at 6 months, 16% at 12 months, and 19% at 24 months. There was a significantly higher rate of recurrence for nodular BCC than superficial BCC (e.g., at 12 months, the recurrence rates were 28% and 13%, respectively, p=0.008). Study findings suggest the use of PDT with superficial BCC and not with nodular BCC. However, there may be confounding factors. For example, the authors noted that nodular BCCs were more frequently located on patients with fewer tumors and that patients with more tumors had a lower risk of recurrence.

Squamous Cell Carcinoma in situ (Bowen’s disease)

In 2003, Salim and colleagues published the results of a trial that randomly assigned 40 patients with Bowen’s disease to undergo either topical 5-FU or MAL therapy. (14) A total of 29 of the 33 lesions (88%) in the PDT group cleared completely, as compared with 22 of 33 (67%) in the 5-FU group. In the 5-FU group, severe eczematous reactions developed around 7 lesions, ulceration in 3, and erosions in 2. No such reactions were noted in the PDT group.

A 2006 multicenter randomized trial with 225 patients (from 40 hospital outpatient dermatology clinics in 11 European countries) compared MAL with cryotherapy or 5-FU for the treatment of Bowen’s disease (squamous cell carcinoma in situ) with lesions on the face or scalp (23%), neck, or trunk (12%), or extremities (65%). (15) Unblinded assessment of lesion clearance found PDT to be non-inferior to cryotherapy and 5-FU (93%, 86%, 83%, respectively) at 3 months and superior to cryotherapy and 5-FU (80%, 67%, 69%, respectively) at 12 months. Cosmetic outcome at 3 months was rated higher for PDT than the standard non-surgical treatments by both investigators and blinded evaluators, with investigators rating cosmetic outcome as good or excellent in 94% of patients treated with MAL-PDT, 66% of patients treated with cryotherapy, and 76% of those treated with 5-FU.

Acne

Literature on the use of PDT for acne consists of several small (n=30 or fewer per group) RCTs from outside of the United States. Results from these initial studies suggest a reduction in lesion count but significant adverse effects of MAL treatment. In one study, 30% of subjects dropped out of the MAL group due to pain. (16)

A 2010 RCT found fewer adverse effects but did not find a clear treatment benefit with a combined intervention of topical 5-ALA and pulsed dye laser treatment. (17) This was a single-blind split-face study and included 44 patients with facial acne. A randomly selected side of the face received the intervention and the other side of the face remained untreated. Patients received up to 3 treatments at intervals of approximately 2 weeks. Twenty-nine patients (66%) completed the 16-week study. For most outcomes, there were no statistically significant differences between the treated and untreated sides of the face. This included change from baseline to 16 weeks in the mean number of inflammatory papules, pustules, cysts, closed comedones or open comedones. There was a significantly greater reduction in erythematous macules on the treated compared to the untreated side of the face (a mean reduction of 5.9 and 2.5, respectively; p=0.04). In addition, the improvement in mean Leed acne severity score was significantly greater on the treated side of the face (-1.07) than the untreated side (-0.52); p=0.001. There were few adverse effects, and they tended to be mild. A limitation of the study was the high drop-out rate.

Other dermatological indications

No controlled studies were identified on PDT therapy for other dermatologic indications. Only case series were identified. Most, such as 2 on hidradenitis suppurativa (18,19) and one on PDT for patients with interdigital mycoses (20) included fewer than 15 patients each. A large retrospective case series was published in 2011 by Xiao and colleagues in China. (21) A total of 642 patients with port-wine stains were treated with PDT; 507 were included in the study, and the remainder were excluded because they had had previous treatment for their lesions or were lost to follow-up. After treatment, 26 (5.1%) of patients were considered to have complete clearing, 48 (9.5%) had significant (<75% to <100%) clearing, and 77 (15.2%) had moderate (<50% to <75%) clearing. This single uncontrolled study is insufficient to draw conclusions about the effect of PDT on health outcomes in patients with port-wine stains.

Summary

Photodynamic therapy refers to light activation of a photosensitizing agent light to produce photochemical effects in the target area. The evidence to date suggests that the net health outcome is better with surgery than with PDT for treating BCC and that PDT for superficial BCC has a similar efficacy to cryotherapy and better cosmetic outcomes. In addition, there is evidence from RCTs that PDT is an effective treatment for selected patients with actinic keratoses of the face and scalp compared to placebo or cryotherapy. There is insufficient evidence that PDT improves the net health outcome for nodular BCC and other dermatological conditions compared to accepted treatments. Thus, PDT may be considered medically necessary for treating selected patients with actinic keratoses, superficial BCC, and Bowen’s disease and is considered experimental, investigational and unproven for all other dermatologic indications.

Practice Guidelines and Position Statements

The 2012 clinical practice guideline on basal cell skin cancers from the National Comprehensive Cancer Network (NCCN) states: “In patients with low-risk superficial basal cell skin cancer, where surgery or radiation is contraindicated or impractical, topical therapies such as 5-fluorourcil, imiquimod, photodynamic therapy (e.g., methyl aminolevulinate [MAL], amino levulinic acid [ALA]), porfimer sodium), or vigorous cryotherapy may be considered, even though the cure rate may be lower.” (22)

In 2008, the British Association of Dermatologists published guidelines containing the following statement on PDT: “Multicentre randomized controlled studies now demonstrate high efficacy of topical photodynamic therapy (PDT) for actinic keratoses, Bowen's disease (BD) and superficial basal cell carcinoma (BCC), and efficacy in thin nodular BCC, while confirming the superiority of cosmetic outcome over standard therapies. (23) Long-term follow-up studies are also now available, indicating that PDT has recurrence rates equivalent to other standard therapies in BD and superficial BCC, but with lower sustained efficacy than surgery in nodular BCC. In contrast, current evidence does not support the use of topical PDT for squamous cell carcinoma...There is an accumulating evidence base for the use of PDT in acne, while detailed study of an optimized protocol is still required.”

The International Society for Photodynamic Therapy in Dermatology published consensus-based guidelines on the use of PDT for non-melanoma skin cancer in 2005. (17) Based on both efficacy and cosmetic outcome, they recommended PDT as a first-line therapy for actinic keratosis. The guideline authors considered ALA to not have sufficient tissue penetration for nodular basal cell carcinoma. Based on 2 randomized-controlled and 3 open-label studies, it was concluded that MAL-PDT can be effective for nodular BCC lesions less than 2 mm in depth, if debulked. The guideline recommended PDT for superficial basal cell carcinoma as “a viable alternative when surgery would be inappropriate or the patient or physician wishes to maintain normal skin appearance.” The report concluded that PDT is at least as effective as cryotherapy or 5-FU for Bowen’s disease but that there is insufficient evidence to support the routine use of topical PDT for squamous cell carcinoma.

Coding

Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps. 

ICD-9 Codes

173.0-173.9, 232.0-232.9, 702.0

ICD-10 Codes

C44.0-C44.9, D04.0-D04.9, L57.0

Procedural Codes: 96567, J7308, J7309
References
  1. Piacquadio DJ, Chen DM, Farber HR 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.
  2. 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 2003; 48(2):227-32.
  3. Hauschild A, Stockfleth E, Popp G et al. Optimization of photodynamic therapy with a novel self-adhesive 5-aminolaevulinic acid patch: results of two randomized controlled phase III studies. Br J Dermatol 2009; 160(5):1066-74.
  4. Morton C, Campbell S, Gupta G et al. Akton Investigators. Intraindividual, right-left comparison of topical methyl aminolaevulinate-photodynamic therapy and cryotherapy in subjects with actinic keratoses: a multicentre, randomized controlled study. Br J Dermatol 2006; 155(5):1029-36.
  5. Szeimies RM, Stockfleth E, Popp G et al. Long-term follow-up of photodynamic therapy with a self-adhesive 5-aminolaevulinic acid patch: 12 months data. Br J Dermatol 2010; 162(2):410-4.
  6. Bath-Hextall FJ, Perkins W, Bong J et al. Interventions for basal cell carcinoma of the skin. Cochrane Database Syst Rev 2007; (1):CD003412.
  7. Szeimies R, Ibbotson S, Murrell D et al. Excilight Study Group. A clinical study comparing methyl aminolevulinate photodynamic therapy and surgery in small superficial basal cell carcinoma (8-20 mm), with a 12-month follow-up. J Eur Acad Dermatol Venereol 2008; 22(11):1302-11.
  8. Basset-Seguin N, Ibbotson SH, Emtestam L et al. Topical methyl aminolaevulinate photodynamic therapy versus cryotherapy for superficial basal cell carcinoma: a 5 year randomized trial. Eur J Dermatol 2008; 18(5):547-53.
  9. Mosterd K, Thissen P, Nelemans P et al. Fractionated e-aminolaevulinic acid-photodynamic therapy vs. surgical excision in the treatment of nodular basal cell carcinoma: results of a randomized controlled trial. Br J Dermatol 2008; 159(4):864-70.
  10. Rhodes LE, de Rie M, Enstrom 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 2004; 140(1):17-23.
  11. 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 2007; 143(9):1131-6.
  12. Foley P, Freeman M, Menter A et al. Photodynamic therapy with methylaminolevulinate for primary basal cell carcinoma: results of two randomized studies. Int J Dermatol 2009; 48(11):1236-45.
  13. Lindberg-Larsen R, Solvsten H, Kragballe K. Evaluation of recurrence after photodynamic therapy with topical methylaminolaevulinate for 157 basal cell carcinomas in 90 patients. Acta Derm Venereol 2011 [Epub ahead of print].
  14. Salim A, Leman JA, McColl JH et al. Randomized comparison of photodynamic therapy with topical 5-fluorouracil in Bowen's disease. Br J Dermatol 2003; 148(3):539-43.
  15. Morton C, Horn M, Leman J et al. Comparison of topical methyl aminolevulinate photodynamic therapy with cryotherapy or Fluorouracil for treatment of squamous cell carcinoma in situ: Results of a multicenter randomized trial. Arch Dermatol 2006; 142(6):729-35.
  16. Wiegell SR, Wulf HC. Photodynamic therapy of acne vulgaris using methyl aminolaevulinate: a blinded, randomized, controlled trial. Br J Dermatol 2006; 154(5):969-76.
  17. 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. J Cosmet Dermatol 2010; 9(1):28-34.
  18. Gold M, Bridges TM, Bradshaw VL et al. ALA-PDT and blue light therapy for hidradenitis suppurativa. J Drugs Dermatol 2004; 3(1 suppl):S32-5.
  19. Schweiger ES, Riddle CC, Aires DJ. Treatment of hidradentis suppurativa by photodynamic therapy with aminolevulinic acid: preliminary results. J Drugs Dermatol 2011; 10(4):381-6.
  20. Calzavara-Pinton PG, Venturini M, Capezzera R et al. Photodynamic therapy of interdigital mycoses of the feet with topical application of 5-aminolevulinic acid. Photodermatol Photoimmunol Photomed 2004; 20(3):144-7.
  21. Xiao Q, Li Q, Yuan KH et al. Photodynamic therapy of port-wine stains: long-term efficacy and complications of Chinese patients. J Dermatol 2011; 38(12):1146-52.
  22. National Comprehensive Cancer Network. Practice Guidelines in Oncology- v1. 2012. Basal cell and squamous cell skin cancers. Available online at: http://www.nccn.org . Last accessed December 2011.
  23. 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; 159(6):35-48.
  24. Centers for Medicare and Medicaid Services. Medicare Transmittal Number 145. Available online at: https://www.cms.gov. Last accessed December 2011.
  25. Dermatologic Applications of  Photodynamic Therapy.  Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2012 January) Medicine 2.01.44.
History
March 2012  Literature review update through December 15, 2011. Rationale extensively re-written. References 13, 19, 21 added; other references renumbered or removed. Indications of acne vulgaris, mycoses, and hidradenitis suppurativa added to investigational statement in policy  
May 2012 Name changed from Photodynamic Therapy to Dermatologic Applications of Photodynamic Therapy. No other changes to policy.
July 2013 Policy formatting and language revised. Title changed from "Dermatologic Applications of Photodynamic Therapy" to "Photodynamic Therapy (PDT) for the Treatment of Actinic Keratoses (AK) and Other Skin Lesions".  Policy statement unchanged.  Added code J7309 and removed 67221, 96570, 96571, J3396, J9600.
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Photodynamic Therapy (PDT) for the Treatment of Actinic Keratoses (AK) and Other Skin Lesions