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INSIDE
Diagnosis and
screening
Staging and
pathological
confirmation
Non-small-cell
lung cancer
Small-cell lung
cancer
Specific clinical
circumstances
Integrating
palliative care
principles

the authors

Lung
cancer

Professor Matthew Peters

senior staff specialist, department
of thoracic medicine, Concord
Hospital, Concord, NSW.

Dr Tajalli Saghaie
clinical associate lecturer,
medicine, Concord Clinical School,
University of Sydney; and consultant
respiratory and sleep physician,
Concord Hospital, Concord, NSW.

Background
BY all reasonable estimates, more
than 90% of the current burden of
lung cancer is related to current or
past active smoking. Smoking risks
are related to age at starting, and
intensity and duration of smoking.
Low-nicotine/low-tar
cigarettes
(sometimes previously marketed as
mild or light) do not reduce lung
cancer risk. Lung cancers associated
with these products may be more
peripherally situated, probably
because deeper inhalation is needed
for nicotine delivery from low-tar
cigarettes.
Reducing the number of cigarettes
smoked is much less beneficial than
complete cessation of smoking. One
study showed that in those who

smoke fewer than 15 cigarettes a

day, reducing the number of cigarettes smoked by more than 50%
reduced lung cancer risk by only
27%.1 After cessation, the risk differential between continuing smokers
and ex-smokers progressively widens with time but the absolute lung
cancer risk of an ex-smoker remains
higher than someone who has never
smoked. However, a smoker quitting at age 40 eliminates 80-91%
of lifetime lung cancer risk and even
quitting at age 50 eliminates 45-67%
of risk. Using nicotine replacement
treatment to aid smoking cessation
confers no lung cancer risk.
Of the remaining 10% of lung
cancer risk, environmental tobacco

smoke may account for many, and

perhaps most, cases in Western
countries. Spousal and occupational exposure clearly increases
lung cancer risk. Most non-smokers
diagnosed with lung cancer in the
current era have lived in periods
when cigarette smoke exposure in
the family home and many community settings was much greater
than now. Of the environmental
air pollutants, diesel particulates
increase lung cancer rates but the
effect is very small compared with
that of smoking.
Therapeutic irradiation to the
lung (such as during treatment
for breast cancer or lymphoma)
increases risk but the effect is either
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only just detectable in non-smokers

or is greatly enhanced by smoking.
The effect is also site-specific so that
the risk is for the lung on the same
side as breast irradiation.
In the background sits genetic
risk. Increasing testing for specific mutations in patients with lung
cancer has identified specific germline mutations, such as the T790M
mutation in the epidermal growth
factor receptor gene that is associated with familial lung cancer
clusters. Very widespread lung cancer genetic testing that is presently
being conducted in France and elsewhere may identify more predisposing germ-line mutations.
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Australian Doctor
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28 March 2014 | Australian Doctor |

23

How To Treat Lung cancer

Diagnosis and screening
THE most important tool in the
diagnosis of lung cancer is clinical
acumen considering lung cancer
as a possible explanation for symptoms. The range of local symptoms that may be related to lung
cancer includes a new or altered
cough, breathlessness, haemoptysis or pain. Systemic features may
include anorexia and weight loss.
Patients with metastatic disease
may also have a range of site-specific symptoms such as seizures or
pathological fractures.
As a general rule, the presence of
symptoms at the time of diagnosis
is associated with more advancedstage disease. Non-smokers tend
to be diagnosed even later because,
not unreasonably, lung cancer is
not considered as an explanation
for early symptoms.
Smokers should be encouraged
to report symptoms. An early
diagnosis increases the range of
possible treatments and their
effectiveness, and may also allow
peace of mind in most cases where
the symptoms are not lung cancer related. Other differential
diagnoses should always be kept
in mind, especially in low-risk
patients, unless they are appropriately excluded. These may include
a myriad of pulmonary conditions
as well as other malignancies.

Initial investigations
The initial investigation in all suspected cases should be a plain chest
X-ray. Previous imaging should be
obtained for comparison whenever
possible. When a chest X-ray reveals
an abnormality that may be lung
cancer, the focus of the clinical interaction must change immediately (figure 1).
Although the preceding clinical
interaction may have been based
on current respiratory symptoms,
the history should be extended to
include past history of other malignancies (if not already known).
Careful physical examination should
be performed looking for abnormal
lymphadenopathy, liver enlargement
and, especially in Australia, lesions
that could be melanoma.
In almost all cases the diagnosis
should be confirmed by pathology.
It is reasonable not to obtain pathological confirmation when there is
comorbidity and a tissue diagnosis
would not lead to specific treatment.

Figure 1:
A plain PA
chest X-ray
showing a
suspicious
coin lesion in
the left lung
field adjacent
to the right
cardiac
border.

Figure 2: CT scan of the chest showing an incidental finding of a solitary

pulmonary nodule in the left lung at the level of the aortic root.
However, it should also be remembered that diagnostic certainty has
value and facilitates other clinical
decision-making.
Making a clinical diagnosis of
lung cancer, even in the presence
of other disease, mandates that the
patient be watched for specific lung
cancer symptoms that require palliative intervention.

Appropriate counselling
When lung cancer appears to be
localised, detailed discussion of
treatment options and prognosis must be politely but firmly
deferred until all relevant diagnostic and staging information is
available.
Many patients will not have
surgically
resectable
cancers,
irrespective of favourable initial
impressions. Knowing the generally adverse course of lung cancer,
doctors can be tempted to describe
the possibility of a surgical cure
prematurely.
This risks taking a patient
through a sequence of anxiety
and despair at the likely diagnosis,
relative euphoria at the prospect
of a curative intervention, then to
despair again.
It is preferable to mention the
range of all possible treatments,
including surgery, chemotherapy
and radiotherapy, and to explain
that the best treatment for the
patients particular case will
become clear after all information is available.

Lung cancer screening

Chest X-rays and sputum cytology
are ineffective tools, but the use of
low-dose CT scans to detect early,
resectable cases in high risk current
and recent ex-smokers holds considerable promise. In the largest study
completed so far, there was both a
reduction in lung cancer mortality
and total mortality when patients
were screened by three annual lowdose CTs vs single-view posteroanterior chest X-rays.2 By way of
contrast, FOBT reduces bowel cancer mortality but does not alter total
mortality.
Recommendations to implement
this strategy at a community level
are reserved, as proper costbenefit
studies as well as other randomised
clinical trials are ongoing. As with
all other screening tests, including
breast and bowel cancer, many positive results are false positive. Consideration of suitability for screening
requires an understanding of the
absolute lung cancer risk, which is
determined by age, current smoking
status, intensity of smoking, period
since smoking cessation (if ceased),
presence of COPD and family or
personal history of cancer. Screening CT should be denied to low-risk
subjects as the risks of radiation and
other consequences of screening
outweigh the reasonable foreseeable
benefits.

Solitary pulmonary nodule

Most small lung cancer nodules are
now detected incidentally in CT

scans done for other purposes or for

symptoms unrelated to the nodule.
It is probable that many patients
have had follow-up CT scans too
frequently for low-risk nodules (figure 2).
First, an attempt at assessing the
individuals lung cancer risk should
be made with one of the various online calculators (see Online
resources). Second, the characteristics of the nodule itself should
be considered. Nodules that are
in the upper lobe, in women, that
are larger, part-solid and seen with
fewer other nodules are more likely
to be malignant. In contrast, small
nodules located close to fissures
and triangular in shape are almost
certainly benign and do not require
follow-up. Despite the selection of
patients for screening and in developing follow-up strategies, lung
cancer cases will present outside the
high-risk group where follow-up is
justified. This problem is not unique
to lung cancer.

Smoking cessation after lung

cancer diagnosis
All medical staff dealing with lung
cancer patients must be able to sensitively but effectively encourage
and support smoking cessation.
Cessation is absolutely necessary
for safe surgical resection.
However, there will be times
when, despite all measures and
support, a patient with resectable
non-small-cell lung cancer (NSCLC)
cannot stop smoking. In these cir-

cumstances, the risks of non-operation need to be carefully weighed

against the increased perioperative
risks and the greater subsequent
risks of recurrence and new primary
tumours with surgery in smokers.
Outcomes after chemotherapy
for small-cell lung cancer (SCLC)
and NSCLC are better in patients
who quit smoking.3-5 Smoking cessation also decreases the risk of
a second primary lung cancer in
those who have extended survival
after treatment.
It is not true that smoking cessation is an unnecessary imposition in
advanced disease, given that it has
been shown to consistently improve
quality of life in that setting and
should be strongly supported.
Using aids
The risks of nicotine replacement
therapy are trivial and their use is
much safer than smoking in any setting. However, bupropion (Bupropion-RL, Clorprax, Zyban SR)
should be avoided unless there is
substantial evidence that the tumour
is localised. This is because the drug
increases the risk of seizure if cerebral metastases are present.
Extending care to family members
Lung cancer risk has an inherited
genetic component, and close relatives who smoke should also be
strongly supported to quit for their
own future health and to increase
the chance that the patient will
quit successfully.

Staging and pathological confirmation

THE dominant predictors of prognosis and determinants of management are histology and staging (table
1). In most cases, establishing histology and staging will proceed in parallel.
Clinicians are encouraged to
evaluate the available information
carefully before planning new investigations. It is always recommended
to plan further investigations in a
way to minimise the number of tests.
This not only limits the cost of care
but also reduces the risk of potential
complications. A procedure that is
likely to provide both a diagnosis
and staging at the same time should
be favoured over a solely diagnostic
procedure. For example, endobron-

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| Australian Doctor | 28 March 2014

Table 1: New staging system for non-small-cell lung cancer6

Stage

Description

Primary tumour is less than 5cm in diameter, located away from all
pleural surfaces and not involving a major bronchus or lymph node
Primary tumours are less than 3cm in diameter, located away from
all pleural surfaces and not involving a major bronchus or lymph
node

1A

Primary tumours larger than 5cm in diameter, with hilar lymph node
or chest wall involvement

3A
3B

Involvement of ipsilateral mediastinal lymph nodes only

Involvement of contralateral mediastinal lymph nodes

Distant disease, typically metastatic to liver, bone, brain, adrenal or

contralateral lung
Cytology-positive pleural effusion are also stage 4 (M1a)

chial ultrasound with transbronchial

needle aspiration (EBUS-TBNA) of
a mediastinal lymph node should be

favoured over a transthoracic needle

aspiration biopsy. In many cases,
when metastatic disease is identified
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Management groupings of
patients from pathology and
clinico-radiological staging
Small-cell lung cancer (SCLC)
amenable to treatment
Non-small-cell lung cancer
(NSCLC) that is localised or only
locally advanced
NSCLC with metastatic disease
Patients with such severe
comorbidity that lung cancer is
not a dominant health issue

in lymph nodes, liver or elsewhere,

biopsy of the metastasis rather than
the primary may be an easier and
safer alternative.
When pathology and clinico-

radiological staging have been

established, the patient will usually
fall into one of four main groups
for management (see box left) that
will require a multidisciplinary
approach. This should include a
respiratory physician, thoracic surgeon, radiation and medical oncologist, and palliative care physician
together with specialist lung cancer
nurses who can provide additional
support and aid the patient in navigating their way through the process
of further assessment and treatment.

CT
Generally, a CT scan from the chest
down, including the whole of the
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How To Treat Lung cancer

from page 24
liver and adrenals, is performed.
Routine radionuclide bone scans
or CT brain scans are not done
in patients without symptoms or
abnormal clinical signs suggestive of
metastasis at the time of diagnosis.

Figure 3: Positive
sputum cytology
for lung cancer,
bypassing the
need for invasive
procedures for
pathological
confirmation.

Sputum cytology
Sputum cytology for malignant
cells is a simple procedure too
often neglected. Although a negative result should not deter clinicians from further investigation,
positive cytology can avoid the
need for invasive procedures (figure 3).

Bronchoscopy
Bronchoscopy is a safe procedure
for the diagnosis of lung cancer
when the lesion is likely to be
endobronchial. Sampling peripheral lesions using an endobronchial
ultrasound with radial ultrasound
probe (figure 4), with or without
assistance from a navigational system is emerging quite rapidly as a
safer alternative to transthoracic

needle aspiration, especially in

patients with significant emphysema. Transthoracic needle aspiration remains the investigation of
choice in pleurally based lesions.
As molecular diagnosis is now
becoming more important, core
biopsies should be obtained whenever practicable.

Pleural fluid sampling

About 10% of lung cancers present with a pleural effusion.

Therefore, pleural investigations

should be considered as means
of diagnosis in this select group
of patients. Thoracentesis and
cytological assessment of pleural
fluid has a variable yield profile
depending on the type of cancer,
but rarely exceeds 60%. Regardless, this low-risk investigation
should be strongly considered as it
provides both diagnostic and staging information. Repeat sampling
significantly increases the yield

Figure 4: An endobronchial ultrasound (EBUS) scope guiding a transbronchial

needle aspiration of a mediastinal lymph node.
Reproduced with permission from Olympus Australia.

in malignant pleural effusions. In

some cases, medical pleuroscopy,
thoracoscopy or even thoracot-

omy could be considered as a diagnostic procedure and as means to

obtain tissue for genetic profiling.

Non-small-cell lung cancer

PET scans
WHEN available, PET scans provide useful information in patients
with NSCLC who are stage 1-3B
on initial clinico-radiological assessments and who are fit for one or
more possible aggressive interventions (figure 5). PET scans may affect
management in many ways (see box
below) by targeting rapidly dividing
cells and correlating highlighted cells
with CT imaging.
However, PET scan findings are
neither perfect nor absolute: the test
results modulate the pretest probability of metastatic disease being
present. For example, the larger the
mediastinal nodes on CT, the more
likely a PET scan will be positive,
but false-negative PET scans are also
more likely in larger nodes.
Therefore, when PET scans indicate mediastinal nodal disease,
pathological confirmation should
generally be obtained. EBUS-TBNA
has largely replaced conventional
mediastinoscopy in staging mediastinal and hilar lymph nodes. As well
as being less invasive, it also provides
access to nodes not previously accessible by mediastinoscopy. It also has
a more favourable safety profile.
In about 10% of patients, additional PET findings lead to fruitless
further investigations or have no
impact on management.

Use of PET scans in NSCLC

PET scans can assist in the management of NSCLC by:
Upstaging patients by identifying unsuspected locally advanced or distant
disease and avoiding futile surgery or aggressive chemotherapy and
radiotherapy treatments
Eliminating suspected sites of metastatic disease and making patients
eligible for treatments with better outcomes
Providing some guidance to the likelihood of malignancy being present in a
solitary pulmonary nodule when biopsy is considered risky
Giving guidance to the state of differentiation of the tumour by the intensity
of fluorodeoxyglucose (FDG) uptake in the primary tumour (high uptake
increases the likelihood of nodal involvement)
Identifying potentially significant, otherwise unsuspected pathology, eg,
renal cell carcinoma, colorectal carcinoma

Figure 5: A FDG-avid right upper lobe pulmonary nodule highlighted on a PET-CT

scan.

Table 2: Risks of lung cancer surgery

Surgery for NSCLC

Surgery for NSCLC is the preferred
modality for treating localised disease (stage 1-2B) with intent to cure;
there is no place for partial resection
or tumour debulking. Preoperative
assessment should include cardiac
and respiratory comorbidities.
Preoperative assessment
An estimate of the expected postoperative FEV1 can be made by
multiplying preoperative FEV1 by
the fraction of ventilated lung segments that will remain after surgery. The general aim is to have
the postsurgical FEV1 >1000mL or
40% of predicted.
Severely impaired diffusing
capacity should encourage cau-

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| Australian Doctor | 28 March 2014

Providing clinicians with a potentially safer biopsy site to obtain tissue

diagnosis

tious assessment of predicted postoperative capacity.

Formal cardiopulmonary exercise testing using a safety threshold
of VO2max >15mL/kg/minute can
be useful to distinguish those at the
highest risk of perioperative morbidity and mortality and of unsatisfactory quality of life after surgical
resection.
The decision to treat surgically

should be made in conjunction with,

or by, a cardiothoracic surgeon who
performs lung cancer surgery frequently, particularly in any case considered marginal.
Extent of surgery
Lobectomy rather than wedge excision is the gold standard. Lesser
resections are associated with higher
local recurrence rates and reduced
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Risk

Counselling

Death

With competent surgery selection, operative technique and

postoperative care, the death rate after lobectomy or left
pneumonectomy should be <1%

Open and shut

procedure

Even with the most up-to-date non-invasive assessment of

intrathoracic tumour extent, some patients will be found to
be inoperable at thoracotomy. Cases may include finding
abnormal vascular anatomy in the chest that precludes
lobectomy, when pneumonectomy is considered an unduly
high risk

Relapse after
an apparent
surgical cure

This is the most significant risk. Even with the most

favourable pre-operative workup and anatomical staging
there are recurrences after apparent complete resection

survival, except for patients aged

over 70 with stage 1A tumours, in
whom outcomes are similar. Nonanatomical lung resections can also
be associated with prolonged postoperative air leaks that can partially
offset the benefit of the lesser resection.
Involvement of the chest wall
(stage 2B) can be treated with en bloc
resection that includes the chest wall.
Chest wall resection should never be
performed when there is concurrent
mediastinal nodal involvement, as
the cure rate is minimal.
Left pneumonectomy is associated with moderate functional
impairment, but function is even
worse after right pneumonectomy.
This deficit needs to be balanced
against the likelihood that the surgery will be curative.

Prognosis after surgery

Counselling about the risks and
benefits of surgery should include at
least the three major risks listed in
table 2, as well as any others pertinent to the individual. In most cases,
patients who have undergone a
lobectomy can be expected to return
to a level of function similar to that
before surgery. This is not true of
patients who have a lung removed
(pneumonectomy).

Stereotactic radiotherapy
Patients with solitary peripheral
1A/1B tumours who are not fit or
willing to undergo surgery should
be offered radiotherapy, given at
high dose with intent to cure. In this
group, radiotherapy should be better tolerated than most because the
tumour is likely to be well separated

make an informed decision. Combination chemotherapy confers a modest survival benefit in patients who
have performance status equivalent
to Eastern Cooperative Oncology
Group (ECOG) level 0 (fully active,
able to carry on all pre-disease
performance without restriction)
or level 1 (restricted in physically
strenuous activity but ambulatory
and able to carry out work of a light
or sedentary nature, eg, light housework, office work).
Both toxicity and the likelihood
of better outcomes are increased
when cisplatin is included in the
regimen. As long as two effective
agents are used in combination,
outcomes are similar. Therefore,
choices between treatments can
be made based on the relevance of
particular side effects for individual
patients and the cost of treatment.
In patients who remain well,
there is no additional benefit in
extending treatment beyond four
cycles. For patients with poorer
performance status but still wishing to consider treatment, singleagent chemotherapy is an option.

from the oesophagus.

Recent advances have made the
option of radiotherapy more appealing, especially in cases where surgery is associated with significant
risks. Stereotactic radiotherapy
significantly limits the area where
treatment is being delivered, and
therefore makes it possible to deliver
higher accumulative doses and plan
for cure.
Placement of fiducial markers
using advanced bronchoscopic techniques such as radial endobronchial
ultrasound has made this treatment
even more accurate. Fiducial markers direct radiotherapy beams to the
target area and can also eliminate
the movement factor when patients
breathe.

Thermal ablation
As with tumours at some other sites,
thermal ablation can be considered
in expert hands to be an alternative to stereotactic radiotherapy in
patients unsuitable or unwilling to
have lung cancer surgery.

Adjuvant treatment after

macroscopic complete resection
Current evidence does not support
adjuvant radiotherapy for patients
who have had a complete lung resection when either hilar or mediastinal
nodes are found to be unexpectedly
involved at the time of surgery.
Adjuvant chemotherapy
For patients with stage 2 or 3A
disease, based on nodal staging
at surgical pathology, adjuvant
chemotherapy with cisplatin-containing regimens confers a survival
benefit of 5-10% at five years.7 The
use of carboplatin instead of cisplatin in chemotherapy regimens has
increased due to its more favourable side-effect profile but there is
uncertainty about the equivalency
of the benefits. Adverse effects on
quality of life are seen with adjuvant chemotherapy for 6-9 months
in contrast to the wait and see
approach.
There is less certainty about the
benefits of adjuvant chemotherapy
in stage 1B (tumours >3cm), for
which results are inconsistent. It
is also uncertain whether benefits
extend beyond the younger, fitter
patients who have been included in
the treatment trials to date, although
this is a reasonable extrapolation.

Initial treatment of locally

advanced disease
Locally advanced disease includes
stages 3A with bulky nodes and 3B
at the time of diagnosis or at relapse
after surgery. This stage of disease
encompasses a broad range of primary tumours and extent of nodal
spread, from microscopic nodal
disease to greatly enlarged nodes
replaced by tumour. It also presents
the most vexed choice of treatments.
Careful integration of radiotherapy,
chemotherapy and surgery is necessary to achieve optimal outcomes
in this group and more research is
needed to generate more accurate
guidance in this area.
Patients with known mediastinal
node involvement are not generally considered for surgery as initial
treatment, unless nodal involvement
is limited to hilar or ipsilateral mediastinal stations (N1/N2 disease).
Therefore careful nodal staging
using PET scans as well as EBUSTBNA or mediastinoscopy are of
paramount importance. However,
in the era before PET scans, similar
patients with metastatic tumour in
nodes that were not enlarged on CT

would often proceed to surgery and

had a five-year survival rate of up to
40%.8

Treatment of advanced nonsmall-cell lung cancer

Problems in treating advanced lung
cancer can occur at initial presentation or during relapse after an apparently curative lung resection. Stage 4
NSCLC requires a holistic approach
in which outstanding life goals and
commitments should influence management. For example, a minimally
symptomatic patient may wish to
travel briefly overseas to see a relative or friend, and the window of
opportunity may be closed if such
a journey were delayed until after
treatment that may ultimately
prove to be ineffective. Importantly,
patients are frequently symptomatic
and management must address
symptoms first and treatment decisions thereafter.
Discussing chemotherapy
All patients with good performance
status should have the opportunity
to discuss the risks and benefits
of cytotoxic chemotherapy and to

Discussing prognosis
Long-term survival is rare, but when
discussing treatment options and
prognosis it should be borne in mind
that a small number of patients do
survive several years, or even longer,
irrespective of management choices.
This provides an honest approach
for the preservation of hope.
Above all else it is important that
treatment plans take into account
the preferences and performance
status of the patient and continuous control of important symptoms.
Radiotherapy should be used when
localised tumour is causing symptoms such as haemoptysis or bone
pain.
Relapse is almost inevitable after
initial treatment. When used as second-line therapy, paclitaxel (Anzatax, Paclitaxel, Taxol) has been
shown to extend survival compared
with best supportive care, but the
benefit is modest and the toxicity is
high.
Recent studies have shown that
patients treated with lower-intensity
paclitaxel and pemetrexed (Alimta)
have similar survival rates compared
with those treated with the higher
doses of paclitaxel used initially, but
experience fewer treatment-related

adverse events and symptoms.

One or other of these regimens
should be favoured because of the
importance of symptom control at
this stage of the disease.
No cytotoxic chemotherapy treatment has been proven effective as
third-line therapy and beyond; it is
proper that patients in this group be
included in ethically justified studies
of novel treatments.

Genetic profiling of lung cancers

Another exciting advancement in
treatment of NSCLC is the emergence of genetic characterisation.
Mutations in more than 15 different
genes are believed to be the driving
oncogene for more than two-thirds
of all non-squamous NSCLCs.
These provide potential treatment
targets.
At present tyrosine kinase inhibitors targeting specific mutations on
the EGFR gene are commercially
available and are associated with
favourable clinical outcomes in
advanced NSCLC. Both erlotinib
(Tarceva) and gefitinib (Iressa) are
shown to be associated with impressive response rates in progressionfree survival in selected patients.
Based on recent randomised controlled trials, erlotinib or gefitinib
should be used as first-line treatment
in advanced NSCLCs (stage 3B and
4) with sensitising EGFR mutations.
Some experience complete tumour
regression that is maintained for
years. However, relapse is considered inevitable and is often seen with
a further or different mutation.
As some mutations are considered
to be responsive and others resistant
to tyrosine kinase inhibitor therapy,
obtaining an adequate tissue sample to allow genetic assessment is
a necessary part of investigations
in lung cancer. Although higher in
prevalence in Asian female nonsmokers, these mutations are by no
means limited to this group. Therefore all tumours with non-squamous
NSCLC should be tested for known
genetic mutations.
Patients with ALK gene rearrangements, found in about 5%
of adenocarcinoma, may experience significant progression-free
survival benefit when treated with
crizotinib (Xalkori). Other targets
are being discovered and targeted
drugs are being developed around
the world.

Small-cell lung cancer

FOR staging and guidance of treatment, SCLC is classified into limited
and extensive disease. In practical terms, limited disease includes
tumours that could be encompassed
in one radiotherapy field.
Although this division has prognostic value, in reality the SCLC is
distributed continuously rather than
as a dichotomy, and prognosis better
follows bulk of disease rather than
dichotomous staging.
Therefore, minimal extrathoracic
disease may have a similar prognosis to bulky intrathoracic disease.
As with NSCLC, it is critical when
managing SCLC that disease-related
symptoms be identified and well palliated at all times.

Limited disease
All patients with limited SCLC and

without major comorbidity should

be offered chemotherapy with a
proven effective treatment regimen.
The best evidence is for platinumbased regimens such as etoposide
(Etopophos, Etoposide, Vepesid)
and cisplatin. Often carboplatin is
substituted for cisplatin because of
its relatively favourable toxicity profile. Intensifying treatment by adding
a third agent increases toxicity but
does not improve outcomes. Maintenance treatment has no value.
Concurrent radiotherapy
Concurrent deep X-ray therapy
to the chest (dose about 40Gy)
improves response rates but is associated with increased toxicity. The
optimal timing for radiotherapy is
about six weeks after chemotherapy
starts; benefit is minimal when deep

X-ray therapy starts after completion

of chemotherapy.
In patients who have had an
apparent complete response, prophylactic cranial irradiation increases
disease-free and overall survival.
Further treatment
Response with partial or complete
tumour regression occurs in about
75% of cases, but relapse also
occurs after weeks to months for
most patients.
Treatment after relapse depends
on the interval since last treatment.
If this is less than three months, the
tumour can be considered resistant
to the first-line combination, and
a new regimen should be selected.
If there is a longer interval before
relapse, the original regimen can be
used again, reserving second-line
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treatment for the later relapse that is

almost inevitable in this group.

Extensive disease
The great majority of patients with
SCLC will have significant symptoms, and these must be identified
and appropriately treated. Patients
with good performance status
should be encouraged to have platinum-based chemotherapy, which
can be expected to reduce tumour
size, provide a survival benefit and
improve symptom control.
However, long-term survival in
extensive SCLC is exceptionally rare.
Second-line chemotherapy should be
limited to the uncommon patients
who have had a good response to
first-line treatment and continue to
have good performance status.
Elderly patients with good perfor-

mance status should be treated with

combination treatment. Responses
are usually good. The role of socalled gentle chemotherapy in
frailer patients is dubious and should
not be used as a substitute for a
frank, honest discussion of the clinical reality.

Surgery in small-cell lung cancer

SCLC is not a surgically treatable
disease. However tempting a given
clinical setting may seem, outcomes
after surgery are poor and it may
delay more appropriate treatment.
When a diagnosis of SCLC is
made only at the time of surgery
for a solitary pulmonary nodule,
standard SCLC treatment should be
administered as soon as is reasonable after recovery from surgery.
contd next page
28 March 2014 | Australian Doctor |

27

How To Treat Lung cancer

Specific clinical circumstances
Cerebral metastases
SINGLE or multiple cerebral
metastases are treated with highdose corticosteroids such as dexamethasone
(Dexamethasone,
Maxidex) 4mg qid. The patient
should be warned about the risks
of agitation and psychosis which,
although uncommon, are distressing and can be mistaken for
tumour-related phenomena.
In most circumstances steroids are followed by whole-brain
irradiation, with the steroid dose
carefully tapered over weeks. If
cerebral metastases are a presenting feature, other tumour treatment should be postponed until
brain disease is reasonably controlled.
In very select cases, when there
is a solitary cerebral lesion and
a resectable stage 1 lung lesion,
sequential resection of the cerebral
lesion and the lung primary can be
considered.
Generally, the development of
more than one cerebral metastasis
in the course of lung cancer care
indicates a prognosis of less than
three months. In the terminal phase
of care, steroids should be stopped
after appropriate discussions.

Superior vena cava obstruction

While superior vena cava obstruction is not a medical emergency,
prompt evaluation and treatment
is required. When present at the
time of diagnosis, a tissue diagnosis should be obtained from
obstructing nodes because while
lung cancer is the most common
cause for obstruction it is not the
only one.
For patients with SCLC, chemotherapy is the optimal initial
treatment and can generally be
delivered more quickly than radiotherapy.

in a patient with only a small primary lung lesion, so it is important

to search carefully for skeletal disease or bulky disease elsewhere;
otherwise, there may be an overlooked alternate explanation for
hypercalcaemia, such as coincidental primary hyperparathyroidism.
Hypercalcaemia of malignancy
has a poor prognosis; survival
beyond several months is unusual.
Symptoms can be distressing and
should be treated using adequate
hydration, IV bisphosphonates,
and care aimed at other specific
symptoms.

Pleural effusion

Radiotherapy is the treatment of

choice for patients with NSCLC
and superior vena cava obstruction at the time of diagnosis.
Stenting procedures have been
reported to be beneficial but the
devices are costly and there is no
meaningful comparative study on
which to form recommendations.

Thromboembolism
Patients with more advanced lung
cancer have the general risks of
DVT associated with reduced
mobility, and also the risk of
tumour-related
thrombophilia.
During periods of hospitalisation
or immobility, local policies for
prophylaxis against DVT must be
followed.
Although the great majority of
events are simple DVT or pulmonary embolism, arterial thrombosis can occur in patients with
thrombophilia secondary to malignancy.
Initial treatment of venous

thromboembolism is with one

of the standard low molecular
weight heparins (LMWH), such
as enoxaparin (Clexane). It is now
clear that in the context of active
malignancy, LMWHs are superior
to oral derivatives of warfarin (eg,
Coumadin) and therefore should
be considered first-line. Novel oral
anticoagulants may provide additional treatment and prophylaxis
options, but their efficacy and
safety in this population are yet to
be established.
In general terms, when anticoagulation is started in the context
of malignancy, it should be continued as long as the underlying cancer is believed to be active.

Hypercalcaemia
SCLC rarely causes humoral
hypercalcaemia (caused by factors
released from cancer cells); this
condition occurs more often with
patients who have NSCLC.
Hypercalcaemia is also unusual

Symptomatic pleural effusions

develop in about 15% of patients
with lung cancer, and dyspnoea
is usually problematic. Simple
aspiration is first-line treatment,
and an initial aspiration of 10001500mL is generally safe. An incessant cough or chest pain, often
radiating to the shoulder tip, during aspiration is a sign of dramatic
change in intrathoracic pressures,
and should be an indication to stop
drainage immediately. Continuing
drainage risks the development of
re-expansion pulmonary oedema
a rare but important complication of large-volume aspiration. It
is important to assess the symptom
response after aspiration and to
establish whether the underlying
lung expands. This is significant
because even in the absence of significant lung expansion, dyspnoea
may be relieved by reducing the
load on the diaphragm.
Pleurodesis
In fit patients, fluid reaccumulation can be controlled by pleurodesis. In this procedure, the
effusion is drained using an intercostal catheter. A sclerosant, such

Integrating palliative care principles

EFFECTIVE management of cancer-related symptoms is available
and should not be delayed waiting
for the development of advanced
disease, to discuss the diagnosis or
to assess the clinical response to
treatment.
In the minds of many people,
palliative care is inextricably associated with terminal care, so discussion of palliative care principles
or referral to a palliative care service needs to be done with considerable sensitivity.
The introduction of opiates for
symptom relief is often seen in the
same way. Individual clinicians
are encouraged to develop their
own script that will allow them
to positively engage patients.

Pain
There is a mistaken perception that
advanced cancer is inevitably associated with prolonged periods of
unrelieved pain, so patients and their
families should be reassured early on
that pain can be relieved safely and
effectively almost all of the time.
Patients should be questioned
about pain during each clinical
review using pain scales to assess
the effectiveness of treatment. Oral

28

| Australian Doctor | 28 March 2014

treatments are generally preferable. Start with short-acting simple

analgesia then convert to regularly
scheduled long-acting formulation when control is established.
An opiate is appropriate if pain is
severe, titrated against sedation.
Constipation occurs almost
invariably; prophylaxis with nonbulking agents should be started
early and bowel function monitored. When pain is not well controlled by analgesics, co-analgesics
such as tricyclic antidepressants or
anticonvulsants may be helpful.
Radiotherapy
Radiotherapy is indicated when
bone pain in one or a small number of sites is causing severe pain
or leading to unacceptably high
opiate doses. A single high fraction
to the site is appropriate when the
appendicular skeleton is involved
but is not likely to be effective for
spinal metastases.
Prophylactic radiotherapy to
avoid fracture should be offered
when a metastasis is identified in a
weight-bearing bone.

Cough and breathlessness

Cough is common and problem-

as talc slurry, is instilled into the

pleural space through the catheter.
The visceral and parietal pleura
become adherent, leaving limited
or no space in which fluid can
accumulate.
The success rate of the pleurodesis depends on the underlying pathology and is higher if it is
performed after fibre optic pleuroscopy or thoracoscopy performed
under general anaesthesia. This
is probably because the pleural
space is better cleared of fluid.
Either procedure allows instillation of talc aerosol spray or talc
poudrage.
Tunnelled pleural catheters
More recently tunnelled pleural
catheters (TPCs) have become
a viable alternative in palliative
management of large symptomatic
pleural effusions, with an aim to
improving patients quality of life
by decreasing hospital admissions
and necessary medical procedures.
As well as promoting patient
autonomy, they also provide a
chance for end-stage patients to
spend more time away from hospitals. They are associated with
fewer complications compared to
talc pleurodesis and repeat thoracentesis and are appropriate in the
less fit category of patients. Interestingly, about half the patients
with TPCs develop pleurodesis,
which in turn allows for removal
of the drain.
Ineffective pleural aspiration
If the initial pleural aspiration has
no clinical or symptomatic benefit
and the patient is not suitable for
a surgical approach, it is best to
leave the pleural effusion alone.
Breathlessness is better palliated
by other means such as opiates in
these cases.

Online resources
atic. Other causes of cough, including COPD and gastro-oesophageal
reflux, should be considered and
treated if found.
Opiates may be required when
the treatment indicated for the
tumour leaves a persistent cough,
but the benefit is modest. Breathlessness is best addressed by
treating any causes that can be
modified using either general or
specific anti-tumour measures
such as pleural fluid aspiration.
Oxygen is commonly prescribed for non-hypoxic patients
with breathlessness, but the benefit beyond a reasonably expected
placebo effect is uncertain. Irrespective of this uncertainty, until
studies are completed, oxygen
should not be withheld.

Haemoptysis
Haemoptysis can vary from minimal to massive. The management
of massive haemoptysis ranges
from exclusively palliative (when
the prognosis is otherwise poor)
to interventional, with airway support and either laser phototherapy
or bronchial artery embolisation.
In less acute settings it is important to consider whether bronchial
www.australiandoctor.com.au

infection has caused or aggravated bleeding, as infection can be

treated more readily than tumourrelated haemoptysis. External
beam radiotherapy is a good treatment option for persistent troublesome haemoptysis.

Central airway obstruction

Management of central airway
obstruction depends on whether
the obstruction is caused by extraluminal nodal disease or intraluminal tumour and whether other
treatments have been exhausted.
For
intraluminal
tumours,
dyspnoea is most rapidly relieved
by laser treatment. This procedure is often followed by placing
a covered intraluminal stent to
prevent recurrence of significant
narrowing. Brachytherapy (radiation delivered on or close to the
tumour) is also effective treatment
but is slower in onset.
Intraluminal
stenting
may
relieve symptoms in some cases
of extrinsic compression. Other
available options include: shaving
the tumour using a rigid scope,
cryotherapy, photodynamic therapy or microdebridement.
contd page 30

Medscape
Solitary Pulmonary Nodule
Malignancy Risk (Mayo Clinic
model)
reference.medscape.com/
calculator/solitary-pulmonarynodule-risk
National Cancer Institute
General Information About NonSmall Cell Lung Cancer
www.cancer.gov/cancertopics/
pdq/treatment/non-small-cell-lung/
healthprofessional

References

Available on request from

howtotreat@cirrusmedia.com.au

How To Treat Lung cancer

Case study

Conclusion

AARON, a 62-year-old exsmoker, presents with a six-week

history of increasing cough. He
had been a long-term smoker of
20 cigarettes daily, but he stopped
smoking at age 58 after a single
episode of rapid AF. He has been
stable in sinus rhythm for the past
two years. He has never had his
lung function measured.
A chest X-ray, performed after
a prolonged increase in his usual
cough after a viral URTI, shows
a solitary nodule in the left upper
lobe 2.5cm in diameter. Aaron has
had a daily cough productive of
clear sputum since the age of 40
but walks 2km daily without chest
pain or dyspnoea.
Physical examination is normal.
Spirometry shows an FEV1 of 2.2L
(72% of predicted) and an FVC
of 3.6L (85%). CT scan confirms
that the lesion is solitary with no
enlarged mediastinal nodes. Liver
and adrenals are normal.
After referral to a thoracic
physician and consideration of
possible diagnoses other than
malignancy, a fine-needle biopsy
reveals NSCLC. A PET scan high-

lighted the lesion consistent with

malignancy, and no abnormal
uptake is seen at other sites.
A provisional diagnosis of stage
1 NSCLC is made and, after discussion with a thoracic surgeon,
left upper lobectomy and lymph

node dissection is performed. The

procedure is uncomplicated and
Aaron is discharged six days after
surgery.
Surgical pathology confirms a
2.5cm primary adenocarcinoma
with involvement of two ipsilateral hilar lymph nodes but no
mediastinal nodal tumour; Aaron
has stage 2A NSCLC.
At the six-week postoperative
visit, he has made a good recovery and is walking 500m daily. He
has been offered participation in
the local pulmonary rehabilitation
program to facilitate return to full
function.
Based on the local data, Aarons
estimated five-year survival is
50-60%, with a potential absolute
benefit of about 5% from adjuvant chemotherapy. He agrees to
have chemotherapy. Neutropenic
sepsis, requiring a six-day hospital
stay, complicated the first of four
courses but the remainder were
well tolerated.
Twelve months after surgery he
is well and has returned to near
his previous level of functional
capacity.

LUNG cancer is the leading cause

of cancer death in Australia. Even
with the most optimistic reduction in
community smoking rates it is likely
to remain so for decades.
Most lung cancer has an adverse
prognosis. Regardless of the mode
of management, long-term survival
is rare. However, early diagnosis
increases treatment options, and
for this reason, smokers should be
encouraged to report any symptoms
as they occur.
Counselling patients in a sensitive
way underpins the GPs role in lung
cancer diagnosis and management. It
is important not to discuss treatment

options and raise a patients hope

until all diagnostic procedures are
complete and the diagnosis is clear.
Helping a smoker who is a lung
cancer patient to quit smoking
is another role that needs to be
handled compassionately. Likewise, discussion of palliative care
options is a delicate area to manage.
After resection or other treatment, some lung cancer patients
are able to achieve a level of function for several years that is almost
comparable to their pre-cancer
state, so a diagnosis should not be
regarded as a death sentence.

Instructions

How to Treat Quiz

Complete this quiz online and fill in the GPevaluation form to earn 2 CPD or PDP points.
We no longer accept quizzes by post or fax.
The mark required to obtain points is 80%. Please note that some questions have more than one correct answer.

Lung cancer 28 March 2014

GO ONLINE TO COMPLETE THE QUIZ

www.australiandoctor.com.au/education/how-to-treat
1. Which TWO statements are correct
regarding risk factors of lung cancer?
a) Smoking greatly increases the risk of cancer
owing to past irradiation
b) Reducing the number of cigarettes smoked
is just as beneficial as complete cessation of
smoking
c) The lifetime risk of lung cancer remains about
50% higher in ex-smokers who quit at the age
of 50 vs lifetime non-smokers
d) Using nicotine replacement treatment to aid
smoking cessation increases the risk of lung
cancer by 30%
2. Which TWO statements are correct
regarding investigations for assessing lung
cancer?
a) A CT assessment of lung cancer should
include the liver and adrenal glands
b) Transthoracic needle aspiration remains the
investigation of choice in suspicious pleurally
based lesions
c) The yield of pleural fluid assessments is
usually less than 10%
d) Sputum cytology is ineffective and should not
be ordered
3. Which TWO statements are correct
regarding the use of PET scanning in nonsmall-cell lung cancer (NSCLC)?
a) PET scans are only useful if the NSCLC is
stage 4
b) One function of PET-CT in NSCLC is in fully
staging patients to avoid futile treatment
c) Once PET scans indicate mediastinal nodal

disease in NSCLC, no further pathological

confirmation is needed
d) In up to 10% of patients additional PET
findings lead to fruitless further investigations
4. Which TWO statements are correct
regarding surgery for NSCLC?
a) Function after right pneumonectomy may be
worse than after left pneumonectomy
b) Tumour debulking surgery is the primary
treatment for stage 1-2B NSCLC
c) Perioperative risk may be assessed with
formal cardiopulmonary exercise testing
looking at the VO2max
d) N
 SCLC that involves the chest wall (stage 2B)
is not suitable for surgery
5. Which TWO statements are correct
regarding the nonsurgical management of
NSCLC?
a) Solitary peripheral 1A/1B tumours that are not
fit for surgery should be offered radiotherapy
b) T
 hermal ablation is ineffective and should not
be offered
c) Adjuvant radiotherapy must be given in all
cases where hilar nodes are found to be
unexpectedly involved at the time of surgery
d) F
 or patients with stage 2 or 3A NSCLC,
adjuvant chemotherapy increases survival
benefit
6. Which TWO statements are correct
regarding the management of small-cell
lung cancer (SCLC)?
a) Surgery remains the primary treatment

for SCLC
b) All patients with limited SCLC and without
major comorbidity should be offered
chemotherapy
c) Concurrent deep X-ray therapy to the
chest may be given about six weeks after
chemotherapy starts
d) Further treatment of SCLC should not be
attempted on relapse
7. Which TWO statements are correct
regarding complications of lung cancer?
a) Dexamethasone to treat cerebral metastases
may cause agitation and psychosis
b) Superior vena cava obstruction is best treated
by stenting
c) Anticoagulation to treat a malignancy-related
DVT should be limited to symptomatic
treatment
d) Hypercalcaemia of malignancy indicates a
poor prognosis
8. Marco is a 43-year-old chronic smoker
who presented requesting screening for
lung cancer because his uncle has just
been diagnosed with lung cancer. Which
TWO statements are correct in addressing
his concerns?
a) Whether Marco is suitable for lung cancer
screening should be considered in the context
of a comprehensive history and examination
b) Marco should be reassured that lung cancer
is due to smoking and no genetic link has
been shown
c) Lung cancer screening with low-dose CT scan

may improve lung cancer mortality

d) Chest X-ray is the most cost-effective
screening tool for lung cancer
9. Marco was found to have a chronic cough
and occasional haemoptysis on assessment.
A chest X-ray was ordered which found a
nodule on his right chest field and ipsilateral
pleural effusion. Which TWO statements are
correct regarding further management?
a) M
 ultiple pleural fluid sampling increases the
diagnostic pick-up for lung cancer
b) Marco should be examined for abnormal
lymphadenopathy, liver enlargement and
lesions that could be melanoma
c) M
 arco should be reassured early that if the
nodule turned out to be a limited lung cancer
it can be well treated
d) Bupropion is useful to help Marco quit
smoking regardless of the diagnosis
10. Marco was found to have stage 4 SCLC.
Which TWO statements are correct
regarding his palliative management?
a) M
 arcos expectations for adequate pain
control in advanced cancer needs to be
tempered
b) Non-bulking agents should be started early
to prevent constipation if opioid analgesia is
prescribed
c) E
 xternal beam radiotherapy is a good
treatment option for persistent troublesome
haemoptysis
d) Oxygen should never be given for
breathlessness

CPD QUIZ UPDATE

The RACGP requires that a brief GP evaluation form be completed with every quiz to obtain category 2 CPD or PDP points for the 2014-16 triennium.
You can complete this online along with the quiz at www.australiandoctor.com.au. Because this is a requirement, we are no longer able to accept
the quiz by post or fax. However, we have included the quiz questions here for those who like to prepare the answers before completing the quiz online.

how to treat Editor: Dr Steve Liang

Email: steve.liang@cirrusmedia.com.au

Next week There are many non-apnoeic conditions that cause excessive daytime sleepiness, such as insomnia, the effect of medications, and narcolepsy. In patients who present in this way, the causes
and management of their condition needs to be considered. This is the topic of the next How to Treat. The author is Dr Anup Desai, senior staff specialist, department of respiratory and sleep medicine,
Prince of Wales Hospital, Randwick; consultant physician in private practice, Camperdown (BMC) and Randwick; and clinical senior lecturer, faculty of medicine, University of Sydney and University of NSW.

30

| Australian Doctor | 28 March 2014

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