• 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.
• Reduction of obstruction and palliation of symptoms in patients with completely or partially obstructing endobronchial non-small cell lung cancer. (NSCLC)
• Treatment of microinvasive endobronchial NSCLC in patients for whom surgery and radiotherapy are not indicated.
• Treatment of high-grade dysplasia in Barrett’s esophagus

• palliative treatment of obstructing esophageal cancer
• palliative treatment of obstructing endobronchial lesions
• treatment of early-stage non-small cell lung cancer in patients who are ineligible for surgery and radiation therapy
• treatment of high-grade dysplasia in Barrett’s esophagus

The following CPT codes may be used to describe endoscopic photodynamic therapy:

96570: Photodynamic therapy by endoscopic application of light to ablate abnormal tissue via activation of photosensitive drugs; first 30 minutes. (List separately in addition to code for endoscopy or bronchoscopy.)

96571: as above, but each additional 15 minutes.

As noted in the CPT code description, the procedure will be coded in conjunction with an esophagoscopy or bronchoscopy, which may be coded as follows:

43228; Esophagoscopy, rigid or flexible; with ablation of tumor(s), polyp(s), not amenable to removal by hot biopsy forceps, bipolar cautery, or snare technique.

31641: Bronchoscopy; with destruction of tumor or relief of stenosis by any method other than excision.

Claims may also be identified by the use of HCPCS code J9600, describing the drug porfimer sodium.

BlueCard/National Account Issues

State or federal mandates (e.g., FEP) may dictate that all FDA-approved services may not be considered investigational and thus these services may be assessed only on the basis of their medical necessity.

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 multicenter, single-arm study of the use of photodynamic therapy in 17 patients with obstructing esophageal cancer. (1) Patients received from 1 to 3 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 2 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 or complete and partial response rates) for the 2 treatments were similar at 1 week (59% photodynamic therapy, 58% laser therapy) with a slight increase in response rates for photodynamic therapy at 6 weeks (60% photodynamic therapy, 41% laser therapy). Clinical improvement, as evidenced by improvements in dyspnea, cough, and hemoptysis, were similar in the 2 groups at 1 week (25%–29%); however, at 1 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 2 techniques had similar effectiveness over a 24-month period. (2) 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 report that photodynamic therapy is associated with successful palliation. (3)

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 3 case series totaling 62 patients with microinvasive lung cancer. The complete tumor response rate, biopsy-proved, at least 3 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. (1) In another case series of 95 early-stage lung cancers, the complete response rate was 83.2%. (4)

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. (5) Patients were followed up closely with repeat endoscopy, with surgical resection if cancer persisted after no more than 2 courses of photodynamic therapy. A total of 9 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’s 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. (6) 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 3 courses of photodynamic therapy separated by 90 days. The primary efficacy endpoint was the complete response rate at any 1 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.

Cholangiocarcinoma

There has been ongoing research interest in photodynamic therapy as an adjunct to endoscopic management of cholangiocarcinoma, primarily as a palliative strategy. In addition, percutaneous biliary drainage is a frequent management strategy for cholangiocarcinoma and PDT can thus be administered percutaneously. Several case series have reported positive results, as measured by quality of life studies. (7-9) Two small randomized studies have reported both palliative effects and an increase in median survival. For example, Ortner and colleagues conducted a trial of 39 patients with nonresectable cholangiocarcinoma who were randomized to receive either endoscopic stenting alone or in conjunction with PDT. (10) The median survival of the 20 patient in the PDT group was 493 days compared to 98 days in the 19 patients who underwent stenting alone. The trial was terminated prematurely due to the favorable results. Zoepf and colleagues randomized 32 patients with cholangiocarcinoma to stenting with and without PDT. (11) The median survival for the PDT group was 21 months compared to 7 months in the control group. There is currently an ongoing NCI-sponsored Phase III randomized study comparing stent placement with and without PDT. The trial is targeted to accrue 120 patients. (12) Currently the National Comprehensive Cancer practice guidelines for the treatment of hepatobiliary cancer do not list photodynamic therapy as one of the treatment options. (13)

2006 Update

A search of the literature focusing on clinical trials published between 2003 through December 2005 did not identify any published studies that would prompt reconsideration of the policy statement; therefore, the policy is unchanged. There continues to be research interest in a variety of applications of photodynamic therapy, including cervical neoplasia, bladder cancer, and soft tissue sarcoma, using a variety of sensitizers. However, the published data still consists of case series and phase I studies. (14, 15) A search of the clinical trials database maintained by the National Institutes of Health identified several phase I or phase II trials involving oncologoic applications of photodynamic therapy. (16) One trial focused on the safety and effectiveness of a novel light sensitizer, texafin lutetium, and 1 trial involved the use of a probe to deliver photodynamic therapy directly into liver metastases. Two trials focused on intraoperative photodynamic therapy as an adjunct to surgical resection of brain tumors.

References:

1. Product insert, Photofrin (Sanofi Pharmaceuticals) www.sanofi-synthelabous.com.
2. 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.
3. 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.
4. Kato H, Okunaka T, Shimatani H. Photodynamic therapy for early stage bronchogenic carcinoma. J Clin Laser Med Surg 1996; 14(5):235-8.
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. Photofrin Package Insert
7. Shim CS, Cheon YK, Cha SW et al. Prospective study of the effectiveness of percutaneous transhepatic photodynamic therapy for advanced bile duct cancer and the role of intraductal ultrasonography in response assessment. Endoscopy 2005; 37(5):425-33.
8. Harewood GC, Baron TH, Rumalla A et al. Pilot study to assess patient outcomes following endoscopic application of photodynamic therapy for advanced cholangiocarcinoma. J Gastroenterol Hepatol 2005; 20(3):415-20.
9. Berr F. Photodynamic therapy for chlangiocarcinoma. Semin Liver Dis 2004; 24(2):177-87.
10. Ortner ME, Caca K, Berr F et al. Successful photodynamic therapy for nonresectable cholangiocarcinoma: a randomized prospective study. Gastroenterology 2003; 125(5):1355-63.
11. Zoepf T, Jakobs R, Arnold JC et al. Palliation of nonresectable bile duct cancer: improved survival after photodynamic therapy. Am J Gastroenterol 2005; 100(11):2426-30.
12. www.cancer.gov/clinicaltrials/UCLA-0501033-01
13. www.nccn.org
14. Yamaguchi S, Tsuda H, Takemori M et al. Photodynamic therapy for cervical intraepithelial neoplasia. Oncology 2005; 69(2):110-6.
15. Kusuzaki K, Murata H, Matsubara T et al. Clinical trial of photodynamic therapy using acridine orange with/without low dose radiation as new limb salvage modality in musculoskeletal sarcoma. Anticancer Res 2005; 25(2B):1225-35.
16. www.clinicaltrials.gov

Hematoporphyrin
Oncologic Applications of Photodynamic Therapy
Photochemotherapy
Photodynamic Therapy
Photodynamic Therapy, Oncologic Applications
Photofrin
Photoradiation Therapy
Photosensitizing Therapy