Autofluorescence Bronchoscopy Improves Staging of Radiographically Occult Lung Cancer and Has an Impact on Therapeutic Strategy

doi:10.1378/chest.120.4.1327

Chest

Volume 120, Issue 4, October 2001, Pages 1327-1332

https://doi.org/10.1378/chest.120.4.1327 Get rights and content

Background

The ability of conventional CT scans and fiberoptic bronchoscopy to localize and properly stage radiographically occult lung cancer (ROLC) in the major airways is limited. High-resolution CT (HRCT) scanning and autofluorescence bronchoscopy (AFB) may improve the assessment of ROLC before the most appropriate therapy can be considered.

Patients and methods

We prospectively studied 23 patients with ROLC, who were referred for intraluminal bronchoscopic treatment (IBT) with curative intent. Additional staging with HRCT and AFB was performed prior to treatment. Twenty patients were men, 9 patients had first primary cancers, and 14 patients had second primary cancers or synchronous cancers.

Results

HRCT scanning showed that 19 patients (83%) had no visible tumor or enlarged lymph nodes. With AFB, only 6 of the 19 patients (32%) proved to have tumors ≤ 1 cm² with visible distal margins. They were treated with IBT. In the remaining 13 patients, abnormal fluorescence indicated more extensive tumor infiltration than could be seen with conventional bronchoscopy alone. Six patients underwent radical surgery for stage T1–2N0 (n = 5) and stage T2N1 (n = 1) tumors. Specimens showed that tumors were indeed more invasive than initially expected. The remaining seven patients technically did not have operable conditions, so they were treated with external irradiation (n = 4) and IBT (n = 3). The range for the time of follow-up for all patients has been 4 to 58 months (median, 40 months). The follow-up data underscore the correlation between accurate tumor staging and survival.

Conclusions

Our data showed that 70% of patients presenting with ROLC had a more advanced cancer than that initially diagnosed, which precludes IBT with curative intent. Additional staging with HRCT and AFB enabled better classification of true occult cancers. Our approach enabled the choice of the most appropriate therapy for each individual patient with ROLC.

Section snippets

Materials and Methods

Twenty-three consecutive patients were referred with the initial diagnosis of ROLC. This was based on the findings of tumors detected intraluminally using conventional WLB that were not visible on standard chest radiographs and standard CT scans with slice thicknesses of 10 mm prior to referral.

HRCT was performed according to the protocol that has been published previously.⁸ WLB and AFB were carried out to inspect the accessible part of the tracheobronchial tree to localize, delineate, and

Results

Follow-up of all patients occurred over a range of 4 to 58 months after the initial diagnosis. In four patients with locally advanced cancers (group A, patients 1 to 4), AFB did confirm the presence of extensive intraluminal tumors, giving a much clearer view of how extensive tumor involvement was. The survival time of the four patients ranged from 4 to 28 months, and they all experienced tumor-related death.

In all six patients (patients 5 to 10) who underwent surgery because occult tumors

Discussion

Woolner et al⁵ showed that in only 29% of patients with early-stage lung cancers detected by sputum cytology could the primary tumor be located by the use of standard radiologic techniques. Two-thirds of these ROLCs are indeed only a few millimeters thick and can be classified as early-stage tumors. WLB relies on the visual judgment of the bronchoscopist. It is important to be diligent in the correct judgment of these minute lesions. Mucosal thickening, swelling, granularity, nodules, and

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Les traitements endoscopiques des cancers in situ ou microinvasifs sont généralement réservés aux contrindications chirurgicales. Différentes modalités thérapeutiques sont potentiellement curatives pour autant que les lésions soient superficielles, peu étendues et in situ ou micro-invasives. Les lésions synchrones sont fréquentes et doivent également être détectées. Les traitements endoscopiques sont également utilisés à visée palliative essentiellement dans le traitement de la dyspnée et cet article de synthèse revoit leurs indications, les résultats actuels et les complications.
Endoscopic management of carcinoma in situ or microinvasive carcinoma of the central airways is generally performed in patients who are not candidates for resection. Curative treatment can be obtained with different techniques and can be expected when the lesion is superficial, of small size and corresponds to in situ or microinvasive carcinoma. Endoscopic treatment is also indicated to relieve airway obstruction in order to palliate dyspnea. This review discusses the indications, the results of different technologies and their complications.
Preinvasive disease of the airway
2017, Cancer Treatment Reviews
Squamous cell carcinoma of the lung arises from preinvasive progenitors in the central airways. The archetypal model appears to be a stepwise morphological progression until there is invasion of the basement membrane. However, not every lesion appears to follow this course and many individuals can have stable disease, or indeed regress to normal epithelium. From our increased understanding of the molecular pathology it is becoming apparent that the respiratory epithelium accumulates progressive genetic and epigenetic insults in response to carcinogens. Still, little is known about how to predict those ‘at risk’ of progression, and it is likely that in the future molecular signatures will underpin prediction models of developing invasive lung cancer. Currently, autofluorescence bronchoscopy gives us the ability to follow the natural history of these lesions, with the prospect that detecting and treating lesions early may improve survival. However, treatment remains controversial, and radical therapies are offered to individuals with carcinoma in situ who may never develop invasive cancer. This has paved the way for the use of minimally invasive bronchoscopic treatments, which, while apparently effective, have not been tested in randomised controlled trials. In this paper we describe the known biology and natural history of preinvasive lesions and review the current treatment strategies.
Interventional bronchoscopy in the management of lung cancer
2016, Revue des Maladies Respiratoires Actualites
Les traitements endoscopiques des cancers in situ ou micro-invasifs sont généralement réservés aux contre-indications chirurgicales. Différentes modalités thérapeutiques sont potentiellement curatives pour autant que les lésions soient superficielles, peu étendues et in situ ou micro-invasives. Les lésions synchrones sont fréquentes et doivent également être détectées. Les traitements endoscopiques sont également utilisés à visée palliative essentiellement dans le traitement de la dyspnée et cet article de synthèse revoit leurs indications, les résultats actuels et les complications.
Endoscopic management of carcinoma in situ or micro-invasive carcinoma of the central airways is generally performed in patients who are not candidates for resection. Curative treatment can be obtained with different techniques and can be expected when the lesion is superficial, of small size and corresponds to in situ or micro-invasive carcinoma. Endoscopic treatment is also indicated to relieve airway obstruction in order to palliate dyspnea. This review discusses the indications, the results of different technologies and their complications.
Advances in imaging probes and optical microendoscopic imaging techniques for early in vivo cancer assessment
2014, Advanced Drug Delivery Reviews
A new chapter in the history of medical diagnosis happened when the first X-ray technology was invented in the late 1800s. Since then, many non-invasive and minimally invasive imaging techniques have been invented for clinical diagnosis to research in cellular biology, drug discovery, and disease monitoring. These imaging modalities have leveraged the benefits of significant advances in computer, electronics, and information technology and, more recently, targeted molecular imaging. The development of targeted contrast agents such as fluorescent and nanoparticle probes coupled with optical imaging techniques has made it possible to selectively view specific biological events and processes in both in vivo and ex vivo systems with great sensitivity and selectivity. Thus, the combination of targeted molecular imaging probes and optical imaging techniques have become a mainstay in modern medicinal and biological research. Many promising results have demonstrated great potentials to translate to clinical applications. In this review, we describe a discussion of employing imaging probes and optical microendoscopic imaging techniques for cancer diagnosis.
Early Lung Cancer. Methods for Detection.
2013, Clinics in Chest Medicine
Citation Excerpt :
AFB has also been shown to increase detection sensitivity of recurrent or new intraepithelial neoplasias and invasive carcinomas when added to WLB (from 25% for WLB alone to 75% when AFB is used in conjunction with WLB) in postoperative surveillance of patients who underwent curative resection for non–small cell lung cancer.32 AFB combined with CT of the thorax in patients with radiographically suspicious and occult lung cancer has shown to be an effective staging and tumor extension assessment modality for lung cancer, with some impact on choice of therapeutic strategy.33,34 AFB can become a useful tool in the screening detection of endobronchial premalignant and malignant lesions, especially in high-risk groups (patients with head and neck cancers and COPD, and smokers), given that the incidence of synchronous lesions ranges from 0.7% to 15% and that metachronous lesions might occur in as many as 5% of high-risk patients annually.35,36
Diagnosis and treatment of bronchial intraepithelial neoplasia and early lung cancer of the central airways: Diagnosis and management of lung cancer, 3rd ed: American college of chest physicians evidence-based clinical practice guidelines
2013, Chest
Citation Excerpt :
These factors may help predict if endobronchial therapy will be successful and identify patients who may require surgery to completely remove the lesion. Sutedja et al78 studied 23 consecutive patients with a diagnosis of radiographically occult lung cancer determined by WLB who were referred for endobronchial treatment with curative intent. Of these, four patients were found to have locally advanced cancers on CT scan of the chest.
Bronchial intraepithelial lesions may be precursors of central airway lung carcinomas. Identification and early treatment of these preinvasive lesions might prevent progression to invasive carcinoma.
We systematically reviewed the literature to develop evidence-based recommendations regarding the diagnosis and treatment of intraepithelial lesions.
The risk and timeline for progression of bronchial intraepithelial lesions to carcinoma in situ (CIS) or invasive carcinoma are not well understood. Multiple studies show that autofluorescence bronchoscopy (AFB) is more sensitive that white light bronchoscopy (WLB) to identify these lesions. In patients with severe dysplasia or CIS in sputum cytology who have chest imaging studies showing no localizing abnormality, we suggest use of WLB; AFB may be used as an adjunct when available. Patients with known severe dysplasia or CIS of central airways should be followed with WLB or AFB, when available. WLB or AFB is also suggested for patients with early lung cancer who will undergo resection for delineation of tumor margins and assessment of synchronous lesions. However, AFB is not recommended prior to endobronchial therapy for CIS or early central lung cancer. Several endobronchial techniques are recommended for the treatment of patients with superficial limited mucosal lung cancer who are not candidates for resection.
Additional information is needed about the natural history and rate of progression of preinvasive central airway lesions. Patients with severe dysplasia or CIS may be treated endobronchially; however, it remains unclear if these therapies are associated with improved patient outcomes.

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Chest

Background

Patients and methods

Results

Conclusions

Section snippets

Materials and Methods

Results

Discussion

References (21)

Lung cancer and chronic obstructive pulmonary disease

Med Clin North Am

Roentgenographically occult lung cancer: pathologic findings and frequency of multicentricity during a 10-year period

Mayo Clin Proc

Relation between bronchoscopic findings and tumor size of roentgenographically occult bronchogenic squamous cell carcinoma

J Thorac Cardiovasc Surg

Detection of dysplasia and carcinoma in situ with a lung imaging fluorescence endoscopy device

Thorac Cardiovasc Surg

Review article: bronchoscopic treatment of lung tumours

Lung Cancer

Occult lung cancer beyond bronchoscopic visibility in sputum cytology positive patients

Lung Cancer

Localization of bronchial intraepithelial neoplastic lesions by fluorescence bronchoscopy

Chest

Assessment of usefulness of endobronchial ultrasonography in determination of depth of tracheobronchial tumor invasion

Chest

Outcome of bronchial carcinoma in situ

Chest

Photodynamic therapy in the management of early superficial squamous cell carcinoma as an alternative to surgical resection

Chest

Cited by (101)

Palliative and curative treatments by bronchial endoscopy

Preinvasive disease of the airway

Interventional bronchoscopy in the management of lung cancer

Advances in imaging probes and optical microendoscopic imaging techniques for early in vivo cancer assessment

Early Lung Cancer. Methods for Detection.

Diagnosis and treatment of bronchial intraepithelial neoplasia and early lung cancer of the central airways: Diagnosis and management of lung cancer, 3rd ed: American college of chest physicians evidence-based clinical practice guidelines

Chest

BronchoscopyAutofluorescence Bronchoscopy Improves Staging of Radiographically Occult Lung Cancer and Has an Impact on Therapeutic Strategy

Background

Patients and methods

Results

Conclusions

Section snippets

Materials and Methods

Results

Discussion

Med Clin North Am

Mayo Clin Proc

J Thorac Cardiovasc Surg

Thorac Cardiovasc Surg

Lung Cancer

Lung Cancer

Chest

Chest

Chest

Photodynamic therapy in the management of early superficial squamous cell carcinoma as an alternative to surgical resection

Chest

Bronchoscopy
Autofluorescence Bronchoscopy Improves Staging of Radiographically Occult Lung Cancer and Has an Impact on Therapeutic Strategy