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PHOTODYNAMIC THERAPY OF EARLY BRONCHOGENIC CARCINOMA. Denis A. Cortese, M.D., Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224

The recent surgical trend has been toward increasingly conservative resections for Stage I lung cancer. This has resulted in a reduction in operative mortality without significant change in survival or recurrence rates. Five year actuarial survival for patients undergoing lobectomy or pneumonectomy for stage I, NO bronchogenic carcinoma range from 69-75 percent (1~2~3) Five year survival of 64 to 69 percent is reported after minimal resection, wedge resection or segmentectomy. (1,2p) Cancer recurrence rates after minimal resection, lobectomy, or pneumonectomy range from 2 to 24 percent for local recurrence (same hemithorax) and from 3 to 29 percent for distance recurrence.(M) Perioperative mortality is reported at 6.2 percent for pneumonectomy, 2.9 percent for lobectomy and 1.4 percent for minimal resection.(”

Surgery is a form of local therapy. It is possible that bronchoscopically based treatment, another form of local therapy, could present an alternative for treating patients with early stage lung cancer. The advantages of bronchoscopic therapy are: reduced risk of surgery for patients who have medical problems; preservation of lung tissue for patients who are at increased risk for metachronous carcinoma (approximately lo-20%); reduced costs.

Photodynamic therapy involves the injection of a photosensitizer such as hematoporphyrin derivative or Photofrin II followed by light radiation which produces toxic oxygen radicals that result in cellular death. This therapy has been used in the treatment of various lung cancers for several years, including several hundred patients with lung cancer. The experience in Japan and the United States treating early stage lung cancer shows that patients with superficial squamous cell carcinoma of the lung have good chance for prolonged complete response.

The recent Japanese experience of treating 49 patients with a total of 59, bronchoscopically accessable early stage lung cancers found that 50 of the cancers (85%) demonstrated a complete response after a single session of PDT. The duration of the complete response was up to 34 months with a mean follow-up of 14 months.@) Local recurrence occurred in five patients ranging from 6 to 18 months after treatment. Prolonged complete response was experienced in 76% of the patients. Cancers less than or equal to 1 cm in length demonstrated the best complete response rate.

Our initial experience treating lung cancer resulted in a complete response rate, up to five years in duration in more than 55% of the patient with roentgenographically occult squamous cell cancers if the cancers were less than 3 cm2 in surface area. More recently, a

P reliminary study of PDT was performed on 13 patients who were surgical

candidates. 9, Thirteen patients, a total of 14 cancers, were treated with the understanding that if cancer persisted after no more than 2 sessions of PDT, performed at 3 month intervals, t.hey would receive standard surgically therapy. In the group of 13 patients, 12 (92 percent) demonstrated a complete response. In total, 13 (93 percent) of the 14 cancers demonstrated a complete response after two sessions of photodynamic therapy. Ten of the fourteen cancers demonstrated a complete response after the first PDT while three other cancers showed a complete response after the second treatment.

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All 13 cancers were superficial and spreading over the mucosa. The single cancer of the 14 (7%) which failed to show a complete response was a bulky, exfoliative lesion. In total, 10 (77%) of the 13 patients were spared resection.

Three patients had resection. The patient with the bulky lesion failed to show a complete response after two sessions of PDT, a lobectomy was performed; the lesion proved to be TlNOMO. The second patient initially had a complete response. After recurrence, it was resected with lobectomy and proved to be a TlNOMO lesion. The third patient’s cancer also initially responded. After recurrence a pneumonectomy was required and the lesion was TlNOMO. During the five years of follow-up one patient (8%) of the 13 died of a second primary lung cancer.

Photodynamic therapy appears to be an alternative to surgical resection in properly selected patients who have early stage bronchogenic carcinoma. A single arm, prospective, multicenter trial has recently been initiated in an attempt to delineate whether PDT will fulfill its promise as a viable alternative to surgical resection.

References

1. 2. 3. 4. 5. 6. 7. 8.

9.

Williams DE, et al: J. Thoracic and Cardiovascular Surg 82:70-76, 1981. Errett LE, et al: J. of Thoracic and Cardiovascular Surg 90:656-659,1985. Little AG, et al: Surg 100:621-628, 1986. Crabb MM, et al: Chest, 99:1421-1424, 1991. Pairolero PC, et al: Annals of Thor Surg, 38:331-338, 1984 Iasconi C, et al: Cancer, 57:471-475, 1986. Ginsberg RJ, et al: J Thoracic and Cardiovascular Surg 86:654-658, 1983. Furuse K, et al: The Japan Lung Cancer Photodyamnic Therapy Study Group. J of Clin Oncology 11(10)1852-7, October 1993. Edell ES, et al: Chest 102:1319-1322, 1992.