Having both small-cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) is relatively rare but possible. Having symptoms of both may lead doctors to diagnose mixed, or combined, cell lung cancer.

Both types of lung cancer share some similarities, but there are also some key differences that define each of the two conditions.

In this article, we look at whether it is possible to have SCLC and NSCLC at the same time, what the research says, the differences between SCLC and NSCLC, diagnosis, and treatment.

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It is possible for a person to have signs of both SCLC and NSCLC at the same time, but it is relatively rare.

Research from 2018 notes that about 5–10% of all SCLC cases are combined SCL carcinoma (CSCLC). This means they show signs of different types of NSCLC as well, including cell types such as:

The main symptoms of CSCLC are:

The risk factors for combined SCLC and NSCLC are similar to those for other lung cancer types.

CSCLC develops in central locations, as well as in peripheral locations in the lungs.

The authors of a 2018 review note that CSCLC is more likely to occur in the peripheral parts of the lungs than SCLC and to produce distant growths from the central location.

The prognosis may improve with CSCLC, as it is more likely for doctors to diagnose CSCLC in earlier stages. Doctors diagnose about 70% of CSCLC cases in the limited stage of the condition.

Treatment for CSCLC can vary. While doctors may begin to follow treatments for SCLC, CSCLC may be resistant to some treatment forms.

A doctor may choose customized options in each case, which typically involves several forms of treatment, such as surgery, chemotherapy, and radiation therapy.

There are several differences between NSCLC and SCLC. These include:

Appearance

The characteristic difference between NSCLC and SCLC is how they look under a microscope. Cancerous cells from someone with SCLC appear small and round. By contrast, cancerous cells from a person with NSCLC appear larger.

Progression

The progression of the two types of lung cancer may also differ.

SCLC can progress rapidly and may be fatal much quicker than NSCLC. Approximately 70% of individuals with SCLC will have cancer that has already metastasized at the time when they receive their diagnosis.

Doctors may categorize SCLC using only two stages: limited and extensive. In the limited stage of SCLC, the cancer is on one side of the chest. In extensive stage SCLC, the cancer has spread to other parts of the chest and to other organs.

Some healthcare professionals may still use further staging for SCLC.

For NSCLC, doctors may use a four-stage system to categorize the cancer:

  • Stage 1: The cancer is only in the lungs.
  • Stage 2: The cancer has spread to nearby lymph nodes.
  • Stage 3: The cancer has spread to the lymph nodes inside the chest.
  • Stage 4: The cancer has spread to both lungs or to other parts of the body.

NSCLC tends to spread more slowly and metastasize to secondary sites.

Location

The location of lung cancer types may vary.

SCLC generally begins in the airways in the center of the chest called the bronchi. NSCLC may originate in other areas of the lung, such as the outer regions that produce mucus.

Treatment

Treatment for SCLC may be different than that for NSCLC. Overall, treatment varies depending on the progression of the disease.

Treatment for SCLC may be more intensive, as SCLC tends to spread faster. Doctors may recommend treatments such as chemotherapy and radiation therapy, as well as preventive treatments in other areas where the cells may spread.

NSCLC treatment may be less aggressive. However, doctors may also diagnose NSCLC at a later stage, which could mean a person needs more intensive treatment to contain the condition.

In the earlier stages, treatment may include surgery to remove a tumor.

People with cancer in later stages may need chemotherapy and radiation therapy.

It is possible for NSCLC to transform into SCLC in some cases. A 2020 case report notes that some cases of lung adenocarcinoma can transform into SCLC after treatment with certain drugs, such as tyrosine kinase inhibitors (TKIs).

Researchers believe it is a resistance mechanism that the cancer uses against certain drugs. In these cases, doctors may recommend a combination of treatments or some other medication.

Diagnosing CSCLC quickly is important to help ensure the most treatment options are available. Doctors who suspect CSCLC may use specific tests to look for biomarkers of the condition.

For example, a 2018 review observes that epidermal growth factor receptor (EGFR) mutations are more common in CSCLC than in SCLC. Finding them may prompt doctors to carry out additional testing.

In other cases, doctors may only suspect combined CLC after treatment begins.

An example would be a case of SCLC that appears to resist chemotherapy or radiation therapy. This may be an indicator of combined CLC and may prompt doctors to take a tissue sample for biopsy.

Treatment for CSCLC can be difficult and will vary in each case, as there are no set treatment models.

Doctors may refer to SCLC treatments and use a few different approaches. They may consider a comprehensive treatment and use a combination of different methods.

If doctors have diagnosed CSCLC, they may recommend surgical resection followed by lymph node dissection if the person’s body is strong enough to undergo surgery. Doctors may also use chemotherapy and radiation therapy to help treat cells left behind or reduce the spread of cancer.

It is still unclear how helpful these additional treatments are for CSCLC compared with SCLC alone. The authors of a 2018 review note that CSCLC may be more resistant to radiation and chemotherapy than SCLC.

However, CSCLC may progress more slowly than SCLC. This means that other options, including surgery, may still be available if doctors can diagnose the cancer early on.

Other drugs, such as EGFR TKIs, may be useful for CSCLC, and ongoing research can help explore these options.

The outlook for an individual with combined NSCLC and SCLC can vary, as the course of the condition itself can differ in each case.

Many factors can affect how the condition progresses.

For instance, the type of combination that occurs may affect a person’s outlook. SCLC combined with spindle cell carcinoma or adenocarcinoma may have a better disease course.

Other factors that may indicate a better course of the condition include:

  • availability of surgical treatment
  • limited spread of the condition
  • lower neutrophil-lymphocyte ratio
  • normal C-reactive protein levels

An improved disease course may give doctors a chance to predict or respond to the condition and provide the best treatments, which could give a person a better outlook.

A 2020 comparative study found that surgeries such as resection, lobectomy, and lymph node dissection may improve the outcomes for people with CSCLC. The study recommends surgery in combination with other methods, whenever possible.

The outlook for CSCLC can differ greatly from person to person, as individual variables play a role in the course of the condition.

It is possible to have both NSCLC and SCLC.

CSCLC may be difficult to treat, as it may be resistant to treatments for SCLC. However, the fact that the condition progresses slowly may also mean that doctors may catch it when surgery is a treatment option.

Treatment may include multiple surgeries and other methods, such as chemotherapy or radiation therapy.