Non-small cell lung cancer may transform into small cell lung cancer during treatment. This transformation affects symptoms, treatment, and outlook.

There are two main types of lung cancer. Their classification is determined by how the cancer cells look under a microscope.

The majority of lung cancers, about 80% to 85%, are non-small cell lung cancer (NSCLC). Most of the remaining lung cancer diagnoses are small cell lung cancer (SCLC), which is much more aggressive than NSCLC.

In some situations, NSCLC can transform into SCLC. Read on below to learn more about the causes of this transformation, how it’s detected, and how it can impact lung cancer treatment and outlook.

Targeted therapy is a type of treatment used for NSCLC. It works by honing in on specific markers associated with cancer cells. As such, it has more precise activity against cancer cells than broad-acting treatments like chemotherapy.

NSCLC can transform into SCLC when it becomes resistant to a type of targeted therapy drug that targets and inhibits epidermal growth factor receptor (EGFR). EGFR is a protein that promotes cell growth and division.

Mutations in the EGFR-coding genes in NSCLC cells mean that more of the EGFR protein is present, boosting cell growth and division. EGFR-targeted drugs can help to reduce this. Some examples of such drugs are:

As treatment proceeds, it’s possible for NSCLC cells to acquire additional mutations that provide resistance to EGFR-targeted therapy. This can drive the transformation into SCLC.

It’s estimated that between 3% and 10% of resistance mutations to EGFR-targeted therapy drugs are related to transformation to SCLC. Some research has found that the time from NSCLC diagnosis to SCLC transformation is about 20 months.

Transformation of NSCLC to SCLC has also been seen in cancers without mutated EGFR as well as in cancers treated with a type of immunotherapy called an immune checkpoint inhibitor.

When NSCLC transforms into SCLC, you may notice a worsening of your lung cancer symptoms. This is because the transformation is associated with resistance to targeted therapy drugs, meaning they won’t work as well.

Some things to look out for include:

It’s known that resistance to EGFR-targeted therapy can occur. So, if you’re prescribed EGFR-targeted therapy for your NSCLC, your care team will monitor you for signs that the treatment has become less effective.

One 2021 study identified a rise in specific tumor markers several months before transformation of NSCLC to SCLC. However, regular screening for these markers for signs of a possible transformation isn’t typically done.

If your doctor suspects that your cancer has transformed, they may order the following tests:

  • CT scan: A CT scan can help your doctor visualize your lungs and surrounding tissues to see if the cancer is progressing.
  • Biopsy: Your doctor can use a recent biopsy of your cancer to see if it has signs of SCLC.
  • DNA sequencing: DNA sequencing can show if additional mutations associated with drug resistance have developed.

Transformation of NSCLC to SCLC will require changes to your cancer treatment. Typically, chemotherapy that targets SCLC is added to your targeted therapy regimen.

SCLC chemotherapy often involves more than one drug. Some regimens that may be used include carboplatin with etoposide or cisplatin and etoposide.

It’s also possible that immunotherapy may be used after NSCLC transforms to SCLC. However, some research has found that the response to immunotherapy in this scenario isn’t as good as it is to chemotherapy.

In general, SCLC is more aggressive than NSCLC. That means that it grows and spreads more quickly. As such, the outlook for NSCLC that transforms to SCLC is typically poor.

A 2021 study reviewed outcomes in 72 people who had NSCLC transform to SCLC. The median overall survival (OS) since the initial NSCLC diagnosis was 27 months.

However, when median OS after transformation was taken into account, it was much shorter at 8.5 months. In their conclusions, the researchers noted that the outlook for transformed SCLC was worse than primary SCLC.

Other studies have supported these findings. One found that median OS was 37 months after NSCLC diagnosis and 13 months after transformation. Another saw that median OS was 28 months after initial diagnosis and 9 months after transformation.

What is a median survival rate?

Median survival rate is a term that refers to the length of time that half of the people with a specific disease are expected to be alive. A median survival rate also means that you have a 50% chance of surviving beyond that time.

In some cases, NSCLC can transform into SCLC. This typically happens after cancer cells gain resistance to EGFR-targeted therapy.

When NSCLC transforms, it typically means that you’ll need adjustments to your treatment plan. This often includes adding chemotherapy that works against SCLC.

SCLC is a more aggressive cancer and the outlook for NSCLC that has transformed is poor. However, each person is different. Because of this, be sure to talk with your care team about what to expect for your specific situation.