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.

• 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.

Local treatment(radiation or

surgery)

Systemic treatment(generally chemo)

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?

• 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.

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.

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 didn’t have an EGFR mutation).

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 isn’t for every patient.

5. Risk from treatment can counterbalance benefit as treatment becomes more intensive.

Conclusions: 5 Key Points for Managing Locally Advanced NSCLC

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