Endoscopic Treatment of Early-Stage Lung Cancer
Endoscopic Treatment of Early-Stage Lung Cancer
Background: Disease-free survival after surgical resection of lung carcinoma in situ has been reported as over 90%. After resection of stage IA non-small cell lung cancer, survival at 5 years is approximately 60% to 70%. If endoscopic or bronchoscopic treatments of early-stage lung cancer can provide similar disease-free survival with less perioperative mortality, morbidity, and cost, then they may be alternative front-line therapies.
Methods: The authors review early-stage lung cancer detection by fluorescence bronchoscopy and the potential treatment of this disease by endoscopic techniques (photodynamic therapy, brachytherapy, Nd:YAG laser, electrocautery, and cryotherapy).
Results: Several reports have noted improved outcomes using endoscopic therapies for early-stage lung cancer, but insufficient data preclude firm conclusions regarding the role of fluorescence bronchoscopy, endobronchial brachytherapy, or electrocautery in early-stage lung cancer. Other than resection, photodynamic therapy may represent the best approach at this time. The principal indication for laser bronchoscopy is palliation of central airway obstruction
Conclusions: The identification of early-stage lung cancer provides no advantage if we have little to offer the patient short of traditional therapy. The value of newer treatment techniques and methods requires verification.
Determining the optimal treatment regimen for lung cancer depends on several factors, including cell type (small cell lung cancer [SCLC] vs non-small cell lung cancer [NSCLC]), stage, and patient performance status. Curative treatment is the main goal; however, most lung cancer patients present with advanced-stage disease, where cure will occur in only a few. For SCLC, chemotherapy is front-line therapy. For stage I or II NSCLC, surgical resection is standard therapy, if the patient can tolerate surgery. Treatment of stage III or IV patients may involve one or more modalities (surgery, chemotherapy, and radiation). This article describes several endoscopic (or bronchoscopic) interventions available to treat early-stage NSCLC, with the intent of cure.
We define early-stage NSCLC as usually lung carcinoma in situ (CIS) - Tis N0 M0, stage 0 in the International System for Staging Lung Cancer, or microinvasive carcinoma. The Armed Forces Institute of Pathology definition of CIS includes malignant cellular changes in the full thickness of the mucosa but an intact basement membrane (Fig 1). CIS is usually squamous cell carcinoma. Microinvasive carcinoma is described as a few millimeters of bronchial invasion but not involving the muscle or cartilage. Perhaps this is truly stage IA. Whether stage IA NSCLC (but probably not IB) should be included in the early-stage definition is debatable.
(Enlarge Image)
Sections show a portion of bronchus. The respiratory epithelium has been replaced by squamous epithelium. The epithelium fails to mature. This is characterized by cytologic atypia extending from the intact basement membrane to the surface. Mitotic figures are present near the surface (arrow). There is chronic inflammation in the stroma below the epithelium.
The rationale for treating CIS is based on the assumption that it will progress to invasive carcinoma and thus treatment at this stage will yield a higher cure rate. The time frame for this progression may span 2 to 10 years, but whether all CIS will progress is unknown. Several investigators have reported that individuals with sputum atypia or dysplasia may develop lung cancer at a rate of 4% to 83% over a period of 5 to 10 years, depending on the severity of the cellular change. Thus, it may be reasonable to treat dysplasia as well, especially if these changes do not normalize after quitting smoking. Since the endoscopic treatments penetrate the airway wall to a limited and unpredictable degree, the extent of cancer invasion will limit the effectiveness of these modalities. Cortese and Edell reported a 7.7% incidence of N1 (nodal) involvement when invasion up to the full thickness of the bronchial wall (5 mm) occurred. Nodal disease is not treatable by current endoscopic modalities.
Even if optimal treatments were available for cellular dysplasia, CIS, or microinvasive carcinoma, a major obstacle is early detection. Patients with these disease stages are usually asymptomatic and radiographically quiescent. Screening patients with sputum cytology continues to generate debate. Regarding radiographically occult lung cancer, Woolner and colleagues reported a CIS incidence of approximately 34%, while Nagamoto et al reported approximately 13%. CIS has been reported to occur concomitantly with a more advanced lung cancer in about 15% of cases. Dysplasia or CIS often produces no visible mucosal abnormalities on conventional bronchoscopy. These findings are often subtle, such as erythema or thickened or granular mucosa. The inability of conventional bronchoscopy to consistently detect early-stage lung cancer has led to the development of fluorescence bronchoscopy in an effort to improve early detection.
Prior to the development of bronchoscopic interventions for early-stage disease, surgical resection was the only treatment. Nagamoto et al reported on resection in 19 lung CIS cases - 18 lobectomies and 1 wedge resection. When followed over 4 to 113 months, 15 patients were alive and disease-free, 2 died of unrelated causes, 1 died of an unknown cause, and 1 developed a more invasive lung cancer. Similarly, Ishida and colleagues reported that only 1 of 11 lung CIS resections developed a more advanced lung cancer, with follow-up ranging from 7 to 152 months; 2 patients died of unrelated cases and 1 died of pulmonary fibrosis. Woolner et al noted only 3 of 28 patients who underwent resection for lung CIS or microinvasive disease developed lung cancer. Perhaps the fact that no controlled trials comparing resection to any of the various bronchoscopic modalities have been reported means that using disease-free survival after resection as the standard to which the bronchoscopic data are compared is a suboptimal comparison at best.
Background: Disease-free survival after surgical resection of lung carcinoma in situ has been reported as over 90%. After resection of stage IA non-small cell lung cancer, survival at 5 years is approximately 60% to 70%. If endoscopic or bronchoscopic treatments of early-stage lung cancer can provide similar disease-free survival with less perioperative mortality, morbidity, and cost, then they may be alternative front-line therapies.
Methods: The authors review early-stage lung cancer detection by fluorescence bronchoscopy and the potential treatment of this disease by endoscopic techniques (photodynamic therapy, brachytherapy, Nd:YAG laser, electrocautery, and cryotherapy).
Results: Several reports have noted improved outcomes using endoscopic therapies for early-stage lung cancer, but insufficient data preclude firm conclusions regarding the role of fluorescence bronchoscopy, endobronchial brachytherapy, or electrocautery in early-stage lung cancer. Other than resection, photodynamic therapy may represent the best approach at this time. The principal indication for laser bronchoscopy is palliation of central airway obstruction
Conclusions: The identification of early-stage lung cancer provides no advantage if we have little to offer the patient short of traditional therapy. The value of newer treatment techniques and methods requires verification.
Determining the optimal treatment regimen for lung cancer depends on several factors, including cell type (small cell lung cancer [SCLC] vs non-small cell lung cancer [NSCLC]), stage, and patient performance status. Curative treatment is the main goal; however, most lung cancer patients present with advanced-stage disease, where cure will occur in only a few. For SCLC, chemotherapy is front-line therapy. For stage I or II NSCLC, surgical resection is standard therapy, if the patient can tolerate surgery. Treatment of stage III or IV patients may involve one or more modalities (surgery, chemotherapy, and radiation). This article describes several endoscopic (or bronchoscopic) interventions available to treat early-stage NSCLC, with the intent of cure.
We define early-stage NSCLC as usually lung carcinoma in situ (CIS) - Tis N0 M0, stage 0 in the International System for Staging Lung Cancer, or microinvasive carcinoma. The Armed Forces Institute of Pathology definition of CIS includes malignant cellular changes in the full thickness of the mucosa but an intact basement membrane (Fig 1). CIS is usually squamous cell carcinoma. Microinvasive carcinoma is described as a few millimeters of bronchial invasion but not involving the muscle or cartilage. Perhaps this is truly stage IA. Whether stage IA NSCLC (but probably not IB) should be included in the early-stage definition is debatable.
(Enlarge Image)
Sections show a portion of bronchus. The respiratory epithelium has been replaced by squamous epithelium. The epithelium fails to mature. This is characterized by cytologic atypia extending from the intact basement membrane to the surface. Mitotic figures are present near the surface (arrow). There is chronic inflammation in the stroma below the epithelium.
The rationale for treating CIS is based on the assumption that it will progress to invasive carcinoma and thus treatment at this stage will yield a higher cure rate. The time frame for this progression may span 2 to 10 years, but whether all CIS will progress is unknown. Several investigators have reported that individuals with sputum atypia or dysplasia may develop lung cancer at a rate of 4% to 83% over a period of 5 to 10 years, depending on the severity of the cellular change. Thus, it may be reasonable to treat dysplasia as well, especially if these changes do not normalize after quitting smoking. Since the endoscopic treatments penetrate the airway wall to a limited and unpredictable degree, the extent of cancer invasion will limit the effectiveness of these modalities. Cortese and Edell reported a 7.7% incidence of N1 (nodal) involvement when invasion up to the full thickness of the bronchial wall (5 mm) occurred. Nodal disease is not treatable by current endoscopic modalities.
Even if optimal treatments were available for cellular dysplasia, CIS, or microinvasive carcinoma, a major obstacle is early detection. Patients with these disease stages are usually asymptomatic and radiographically quiescent. Screening patients with sputum cytology continues to generate debate. Regarding radiographically occult lung cancer, Woolner and colleagues reported a CIS incidence of approximately 34%, while Nagamoto et al reported approximately 13%. CIS has been reported to occur concomitantly with a more advanced lung cancer in about 15% of cases. Dysplasia or CIS often produces no visible mucosal abnormalities on conventional bronchoscopy. These findings are often subtle, such as erythema or thickened or granular mucosa. The inability of conventional bronchoscopy to consistently detect early-stage lung cancer has led to the development of fluorescence bronchoscopy in an effort to improve early detection.
Prior to the development of bronchoscopic interventions for early-stage disease, surgical resection was the only treatment. Nagamoto et al reported on resection in 19 lung CIS cases - 18 lobectomies and 1 wedge resection. When followed over 4 to 113 months, 15 patients were alive and disease-free, 2 died of unrelated causes, 1 died of an unknown cause, and 1 developed a more invasive lung cancer. Similarly, Ishida and colleagues reported that only 1 of 11 lung CIS resections developed a more advanced lung cancer, with follow-up ranging from 7 to 152 months; 2 patients died of unrelated cases and 1 died of pulmonary fibrosis. Woolner et al noted only 3 of 28 patients who underwent resection for lung CIS or microinvasive disease developed lung cancer. Perhaps the fact that no controlled trials comparing resection to any of the various bronchoscopic modalities have been reported means that using disease-free survival after resection as the standard to which the bronchoscopic data are compared is a suboptimal comparison at best.
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