Core Principles of Managing Locally Advanced

Non-Small Cell Lung Cancer (NSCLC)

H. Jack West, MD

Locally Advanced, also known as Stage III

NSCLC, may be treated in any of several ways
There is no single best treatment for patients
with locally advanced NSCLC. In general, it requires
a combination of treatment for local disease that
you can see, as well as potential distant disease
that you cannot.
Local treatment
(radiation or
surgery)

Systemic treatment
(generally chemo)

Higher T (tumor) stage tends to be associated with

greater risk of local disease. Higher N (nodal) stage
and greater number of nodes tends to be
associated with greater risk of distant disease.

Multimodality Therapy: A Team Approach

Because optimal treatment of
locally advanced NSCLC is
multimodality (requires a
combination of chemo with
radiation or surgery or both), it is
ideal to have treatment plans
developed by a team of
specialists in these fields prior to
staring therapy.

Recommendations may vary from patient to patient

based on size of the cancer, its location, T stage, N
stage, health of the patient, and other factors.

Hot Light, Cold Steel: Is Surgery the Path

to Cure in Locally Advanced NSCLC?
Not necessarily. Chemo and
radiation combined together
produces comparable survival
to surgery for stage IIIA and
IIIB NSCLC overall and is NOT a
consolation prize.
Surgery is sometimes recommended for patients with stage IIIA
disease and non-bulky N2 nodes on the same side as the
main tumor in the mid-chest (mediastinum). This is typically
preceded by induction chemo or chemo and radiation.

Chemo and radiation, without surgery, are considered more

appropriate when there are many areas of nodal involvement,
bulky lymph nodes, or N3 nodes in the mid-chest opposite
the main tumor.

Chemo/Radiation without Surgery to

Cure Locally Advanced NSCLC

Originally, only radiation or surgery were

used for locally advanced NSCLC.
Unfortunately, only a small minority of
patients with stage III NSCLC were cured
of their cancer (about 5%).

Chemo was then added sequentially (preceding radiation),

improving survival at 3-5 years (to about 10%). It can help treat
invisible, distant disease in addition to the visible disease
treated with local therapy.
Administering chemo concurrently with radiation can improve
cure rates (~15-25%). Chemo acts as a radiosensitizer,
increasing efficacy of the radiation. The most common chemo
regimens combined with radiation are cisplatin/etoposide or
carboplatin/Taxol (paclitaxel), but others can be used.

Balancing Efficacy with Safety

Stage III NSCLC has a high risk of recurrence/progression
through treatment. Combining chemotherapy with radiation
and/or surgery to treat the cancer aggressively has the
potential to improve the cure rate against the cancer, but it
also increases the side effects of treatment.
These can sometimes be life-threatening, or even fatal. Even
in carefully conducted studies, about 5-7% of patients can die
from treatment, and more or left with significantly
compromised lung function.
Beyond a certain level (that varies with
the health of the patient), escalating
intensity of treatment may cause more
harm than good and worsen survival.

Too much of a good thing?

A key clinical trial compared about 6.5-7 weeks of daily chest
radiation (Mon-Fri) to a longer course and higher dose with
concurrent chemotherapy. This showed that more radiation was
associated with WORSE survival than the standard dose.
The best studied chemo is about 6-7 weeks, either two courses
of every 3-4 week cisplatin/etoposide or 7 low weekly doses of
carboplatin/Taxol. Giving additional chemo before or after this
has never been shown to be better (though we often give it,
hoping it could be). Taxotere (docetaxel) after chemo/radiation
increased side effects but not survival.
There is no role established for targeted therapies in locally
advanced NSCLC. Iressa (gefitinib) was significantly harmful,
worsening survival, after chemo/radiation in an unselected
population (most didnt have an EGFR mutation).

Conclusions: 5 Key Points for Managing

Locally Advanced NSCLC
1. Optimal treatment is individualized to the patient and their
cancer but almost always involves two or three modalities of
therapy (chemo, radiation, surgery).
2. A multimodality plan should be developed by a group of
specialists considering the range of combined therapy options.
3. Surgery may have a role in more limited, less bulky stage III
NSCLC (almost always stage IIIA). A nonsurgical approach with
chemo/radiation can lead to comparable survival.
4. Concurrent chemo and chest radiation (as an alternative to
surgery) leads to improved survival compared with sequential
treatment but isnt for every patient.
5. Risk from treatment can counterbalance benefit as treatment
becomes more intensive.

For questions, comments, and

further information, check out
CancerGRACE.org