DOI: 10.
1093/annonc/mdf666
Interventional palliative treatment options for lung cancer
M. Noppen
Academic Hospital, Interventional Endoscopy Clinic, Respiratory Division, Brussels, Belgium
Introduction
The burden of lung cancer on public health is enormous: about
13% of all new cancers in the world are lung cancers and the
numbers increase at a rate of about 3% a year. Worldwide,
lung cancer is by far the most common cancer in males
(19–21% of all new cancers) and the fifth most frequent
cancer in females (5% of all new cancers) [1]. The worldwide
impact of lung cancer will furthermore increase, as tobacco
companies concentrate their marketing efforts on developing
countries.
Despite all current efforts in prevention (smoking cessa-
tion), early detection [e.g. spiral computed tomography (CT)
scan screening in populations at risk] and early treatment,
development of new chemotherapeutic agents and combined-
modality treatments involving chemotherapy, surgery and
radiation therapy, the overall prognosis of lung cancer is still
dismal, with 5-year survival remaining at about 13% over the
last few decades. Because of this high fatality rate, lung cancer
now accounts for almost 30% of all cancer deaths in males [1].
At the time of diagnosis, only about 20–25% of lung cancers
can potentially be cured, primarily by surgery [2]. Every
clinician should therefore realize that for the large majority
of patients presenting with locally advanced or metastatic
disease, treatment essentially remains palliative, consisting of
external beam irradiation, chemotherapy or a combination of
both.
Every clinician caring for lung cancer patients should
realize that 20–30% of all patients present with neoplastic
major airway obstruction (with resulting atelectasis, pneumo-
nia) [3] and that after initial treatment, 30–50% of patients
present local recurrences [4]. Furthermore, about 30% of all
lung cancer patients eventually develop some form of
bronchial hemorrhage [5].
Finally, the majority of patients with final stage central air-
way tumors will suffer from dyspnea and cough (e.g. because
of atelectasis or post-obstructive pneumonia) [6], a consider-
able number of which can be palliated by means of inter-
ventional bronchoscopic procedures [2, 4, 5, 7].
Although such procedures may improve survival in selected
cases [2], and even be curative in cancers restricted to the air-
way walls [5], their main purpose remains the improvement of
symptom control and quality of life.
© 2002 European Society for Medical Oncology
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A large variety of different endoscopic (flexible as well as
rigid) treatment modalities are now available, and their utility
in controlling local tumor progression has been proven [8].
Indications for interventional bronchoscopic
procedures in lung cancers
Major indications for endobronchial treatment in lung cancer
include:
• life-threatening obstruction of the central airways (trachea,
carina, main bronchi);
• central airway obstruction causing symptoms (dyspnea, ate-
lectasis, post-obstructive pneumonia, hemoptysis or reduc-
ing the airway lumen >50%) and
• inoperable early lung cancer amenable to endoscopic treat-
ment.
This paper will focus on the first two indications, although
the techniques and instruments used are also applicable to the
third category of patients.
Principles and techniques of endoscopic
treatment
The principles of palliative bronchoscopic treatment are:
• to reopen obstructed airways (and, hence, relieve dyspnea,
post-obstructive infection and atelectasis);
• to maintain established airway patency (and, hence, prevent
recurrence of obstructive symptoms, and to allow for con-
comitant non-endoscopic therapy such as chemo/radiother-
apy which often are contraindicated in cases of post-
obstructive complications) and
• to treat specific symptoms (e.g. hemoptysis, cough, ...).
Different endoscopic techniques can hence be classified
relative to the abovementioned treatment principles and
indications:
• Techniques enabling rapid removal of obstruction (e.g.
mechanical debulking/resection, ND:YAG-laser resection,
electrocautery) in case of life-threatening obstruction.
• Techniques enabling delayed removal of obstruction
(e.g. cryotherapy, endobronchial irradiation, photodynamic
therapy) in cases of non-critical stenosis.
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• Techniques enabling maintenance of airway patency (e.g.
stenting).
• Techniques enabling symptom control such as hemoptysis
(e.g. argon plasma coagulation, electrocautery, ND:YAG-
laser therapy, ...).
• Techniques for increased local tumor control (e.g. intra-
tumoral injection of gene therapy vectors).
The choice of the initial endoscopic treatment technique
depends on various factors:
• The urgency of the intervention (e.g. imminent suffocation);
• The nature and extent of the obstruction (e.g. intraluminal
versus extraluminal disease);
• The available equipment, expertise and logistics.
Techniques and instruments
Mechanical removal of obstruction
In cases of life-threatening central airway obstruction, rapid
mechanical resection of intraluminal, exofytic tumor tissue by
rigid bronchoscopy ‘curettage’ and/or forceps resection is a
well-established technique [8]. Provided functional lung par-
enchyma can be recruited, and the pulmonary artery is open,
this procedure may provide instant relief. However, because
bleeding is inevitable, which may compromise gas exchange,
coagulation methods should be applied prior to mechanical
removal. ND:YAG-laser, electrocautery, cryotherapy or other
techniques may be used for this purpose.
Immediate hemostasis can often be obtained by mechanical
airway wall compression using the rigid bronchoscope shaft.
Endobronchial laser therapy
The most widely used and most versatile laser for endobron-
chial treatment is the Nd:YAG (neodymium-yttrium aluminum
garnet) laser, using an infrared wavelength of 1064 nm. The
thermal energy of the laser light is used: the interactions of
laser heat and treated tissue are dependent upon the absorption
characteristics of the tissue, the power output of the laser, the
distance between the laser tip and the tissue, the working
angle, and the time of laser application [5, 9].
Depending on these factors, coagulation, vaporization or
cutting can be obtained. Most often, Nd:YAG-laser therapy
is used to coagulate and devascularize endoluminal tumors,
immediately prior to mechanical resection. Hence, laser therapy
most often is performed through a rigid bronchoscope.
The main complications of Nd:YAG-laser therapy include
hemorrhage (1–10%), airway wall perforation and pneumo-
thorax (3%), transient desaturation and burns. Although rigor-
ous application of preventive measures keeps complications
to a minimum, successful laser therapy requires considerable
expertise. Nevertheless, this technique is safe and efficient in
experienced hands, and has become the ‘gold standard’ for
palliative treatment of endoluminal airway obstruction. In
view of the high costs of purchase and maintenance, however,
electrocautery may well replace laser therapy in the future as
the ‘first-line’ interventional technique [10].
Electrocautery
Similar to Nd:YAG-laser therapy, electrocautery is based on
the local application of heat, using electrical current via a
dedicated probe, to coagulate or vaporize tissue. Electric
current is generated with a standard high-frequency electric
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generator, which is available in any operating theatre. In bron-
chology, unipolar probes (including blunt probes, wire snares,
forceps, ...) can be used via flexible and rigid bronchoscopes.
The indications and principles of application are essentially
the same as for Nd:YAG-laser therapy. Its major advantages
compared with laser therapy are its very low cost, despite
equal levels of efficiency, and probably superior levels of
safety [5, 10, 11].
Argon plasma coagulation (APC)
Argon plasma coagulation is a non-contact mode of electro-
coagulation: argon gas is ejected around a high-frequency
electrode. The ionized gas serves as a conductor between the
electrode and the nearest tissue. A spark through the plasma
jet desiccates and coagulates the tissue. A major advantage of
APC is the fact that the nearest area of contact is not neces-
sarily geometrically straight forward from the direction of the
electrode, because the high frequency current follows the
lowest electrical impedance. Hence, bleeding (wet) lesions
‘attract’ the argon jet: superficially bleeding lesions are there-
fore the ideal indication for APC. Its superficial action makes
APC a safe technique, but also less efficient than Nd:YAG-
laser or simple contact electrocautery in the treatment of bulky
lesions [2, 12, 13].
Cryotherapy
Cryotherapy is the application of extreme cold for local
destruction of living tissue. Two mechanisms of injury are
associated with cryotherapy. Rapid freezing produces intra-
cellular ice crystals which are lethal to the cell. As tissue
thaws, a second mechanism of injury becomes operative: the
circulation of the previously frozen area is restored, but pro-
gressive failure of the microcirculation due to endothelial cell
damage and thrombosis occurs. With failure of circulation, a
larger volume of tissue death will occur [2, 14, 15].
Hence, after cryotherapy, no immediate removal of obstruc-
tions can be carried out: only hours to days after application
can debris be removed (either spontaneously or by ‘clean-up’
bronchoscopy). Therefore, cryotherapy should not be used to
treat severe, life-threatening airway obstruction. The effect of
cold is tissue-specific: depending upon their water content and
degree of vascularization, some tissues are cryosensitive
(tumor cells, granuloma, ...) whereas others are cryoresistant

(fibrous tissue, cartilage, ...). Airway wall perforation there-
fore is virtually non-existent, making cryotherapy a safe tool.
Indications for cryotherapy include treatment of non-critical
malignant airway obstruction and hemoptysis. Other indica-
tions are treatment of superficial early lung cancer and
removal of (water-containing) foreign bodies. Results are
comparable to other techniques that remove obstructions, and
complication rate and costs are low.
Photodynamic therapy
Photodynamic therapy (PDT) involves the intravenous injec-
tion of a (more or less) tumor-specific photosensitizing agent
(e.g. porfimer sodium, photofrin), followed by activation of
the agent by exposure to laser light of a specific wavelength
(630 mm) administered by means of flexible bronchoscopy.
After photosensitizer activation, a photochemical reaction
with production of reactive oxygen singlets destroys tumor
cells. Approximately 48 h later, a ‘clean-up’ bronchoscopy is
required to remove debris [5, 16].
Photodynamic therapy can be used in the palliative treat-
ment of non-critical obstructive malignant tumors of the air-
ways; its local results are comparable with Nd:YAG-laser,
allowing for somewhat slower but longer-lasting effects. In
the palliative context, however, its use is limited by the pro-
longed and sometimes severe photosensitization of skin and
eyes, leading to a severe reduction in quality of life, and by its
high cost. The advantages of PDT are its possible use in
lesions located on the relative periphery of the airways which
are accessible by flexible bronchoscopy, and its potential
curative treatment of early superficial lung cancer.
Endobronchial irradiation (brachytherapy)
Endobronchial irradiation is currently achieved by placing a
highly radioactive source (iridium 192 probe, hence ‘high
dose rate’ or ‘HDR’) through a hollow catheter (hence, ‘after-
loading’) which is positioned by means of a flexible broncho-
scope at the desired location (hence, ‘brachytherapy’) [5, 17].
HDR treatment is usually delivered with one to six fractions at
an interval of 1–3 weeks and a dose of 2–30 Gy per fraction at
1 cm from the source axis. The optimal dosage regimen and
frequency are undetermined as yet. Endobronchial irradiation
can be used for potentially curative treatment of early super-
ficial lung cancer, for treatment of primary non-resectable
bronchial carcinoma with curative intent and for palliative
treatment involving the removal of obstruction for primary or
recurrent endoluminal lung cancer. Its results are comparable
with other ‘late onset’ treatments to remove obstructions.
HDR brachytherapy can be performed on an outpatient basis,
combined with other treatment modalities, and is well toler-
ated. Its main disadvantages are its high procedural and infra-
structural costs, and the possibility of severe radiation fibrosis
or (fatal) hemorrhage.
249
Endobronchial stenting
Airway stents are used in the palliation of lung cancer for
maintaining patency of otherwise (cfr. supra) reopened
airways, for securing patency of a collapsed or extrinsically
compressed central airway, and for sealing of fistulas [5, 7,
18–20]. Minor indications include, for example, control of
hemoptysis. Numerous types of stents are available. They can
be classified according to material (polymer stents, metallic
stents, hybrid stents and covered metallic stents), insertion
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technique (rigid bronchoscopy, flexible bronchoscopy, fluoro-
scopical), type (self-expandable, fixed diameter) or anatom-
ical position (bifurcation, stump, trachea, bronchus). The ideal
stent does not exist; the best stent for a specific patient present-
ing with a specific problem should be identified. Judicious
stent placement undoubtedly improves quality of life and
sometimes even survival.
Side-effects and complications include bacterial coloniza-
tion, migration, granuloma formation, tumor overgrowth,
stent rupture and (rarely) wall perforation.
Impact of interventional palliative treatment
As pointed out in the introduction, the majority of patients
suffering from lung cancer will die from the disease. The vast
majority of treatment efforts (chemo- and radiotherapy, inter-
ventional bronchoscopy) are therefore palliative [21].
As compared with chemo- and radiotherapy, which give rise
to a huge body of randomized comparative trials—mainly
driven by the enormous investments of the pharmaceutical
and technological industry—interventional bronchoscopy is
still considered a kind of ‘playground’ for a peculiar kind of
creative, skillful, handy-man-like pulmonologist, which is
often not taken very seriously by those who work in the field
of oncology. Nevertheless, although many studies devoted to
the impact of interventional bronchoscopy on cancer treat-
ment are often ‘how-I-do-it’ case series with all their pertain-
ing flaws, it is most likely that many of the conclusions drawn
from these studies can be generalized to most patients with
central airway obstruction [21]. It is well proven now that
restoring central airway patency has a significant impact on
symptoms, pulmonary function, quality of life, and—in
selected patients—even on survival [21]. Today, even per-
forming a randomized study of interventional bronchoscopy
using a no treatment arm is considered unethical.
Future projects
Today interventional bronchoscopy is a performant tool in the
palliative treatment of inoperable lung cancer, and is well-
established in the pulmonological world [2]. What is urgently
needed, however, is greater acknowledgement of this treat-
ment tool by the specialists in oncology. This will automat-
ically lead to integrational studies on interventional techniques
in the algorithmic approach of the inoperable lung cancer
250
patient. Indeed, interventional pulmonologists are too often
considered the ‘last hope’ for widely evolved, (pre)terminal
lung cancer patients. An earlier application of interventional
techniques in the management of these patients, in collabora-
tion with chemo- and radiotherapists, will most probably have
a larger impact on quality of life (and probably on survival),
than each treatment on its own. This is what we, interventional
pulmonologists, consider true multimodality treatment of
inoperable lung cancer.
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