Surgery is the standard treatment for early stage lung cancer, sometimes also including other types of threrapy in addition. There are many types of lung cancer surgery, and there is still active debate about whether a pneumonectomy or lobectomy should be the preferred surgery for lung cancer, or whether a sub-lobar resection, either a segmentectomy or a wedge resection, is appropriate for certain patients. We need to start with some definitions.

Chemotherapy after surgery has become increasingly well established as beneficial for many patients who have undergone surgery for early stage NSCLC, at least for stage II and IIIA resected disease (stage IB has had more mixed results and remains quite debatable). The chemo regimens that have been most clearly shown to confer improved survival are cisplatin-based and can have very challenging toxicity in anybody, especially after a major lung surgery.

In contrast to the guidelines that exist for treating advanced lung cancer in the first-line setting for 4-6 cycles, there are really just practice patterns and good judgment to guide decisions of how long to treat in the second-line therapy. First, this is a relatively new question. As I previously mentioned when describing the history of treatment for advanced lung cancer, ten years ago there was plenty of debate about whether the benefits of treating NSCLC were sufficient to make this a standard of care.

The guidelines from the American Society for Clinical Oncology (ASCO) for NSCLC start the discussion on how long to continue first-line chemo as follows: "The optimal duration of chemotherapy remains a matter of debate." Just in case you thought it was only me saying that we don't know the exact answer for one issue or another, the evidence-based guidelines are filled with hedge comments like this.

We've come along way over the past decade. In the first half of the 1990s, the value of treating metastatic NSCLC was debated and not clear. A "meta-analysis" that pooled the results from 11 chemotherapy trials, 8 with cisplatin, and nearly 1200 patients demonstrated a modest but convincing improvement in survival compared to supportive care alone (article here). The figure summarizing the improvement by adding chemo is shown here:

As I mentioned in my introduction to the topic, SCLC is typically sensitive to chemo and radiation initially, but it tends to be considerably less responsive after recurrence. Unfortunately, most SCLC patients, or about 75-80% of patients with LD-SCLC and nearly 100% of patients with ED-SCLC , do subsequently recur.

For patients with locally advanced NSCLC, the question of whether to pursue a surgical or a non-surgical approach has a great deal to do with the extent of mediastinal (middle of the chest) lymph node involvement. The mediastinal nodes are shown here:

As I described in a post describing the general principles of SCLC, it is typically responsive to treatment initially, but upon recurrence it is much less likely to respond.

The oral EGFR inhibitors Iressa and Tarceva both have activity in advanced NSCLC, with proven responses in a minority of patients and improvements in cancer-related symptoms as well.

Both standard chemotherapy and EGFR tyrosine kinase inhibitors (TKIs) have been approved in NSCLC, and other anti-EGFR agents like erbitux/cetuximab and vectabix/panitumumab are also commercially available for treating other cancers and are being studied in lung cancer. Iressa was previously approved as a single agent in previously treated patients with advanced NSCLC, and Tarceva is now available but approved also as a single agent therapy. However, some oncologists give EGFR inhibitor therapies in combination with standard chemo.