The Difference Between Small Cell and Non-Small Cell Lung Cancer

The Difference Between Small Cell and Non-Small Cell Lung Cancer

If you've received a lung cancer diagnosis, it can be confusing. What does it mean and what treatments are available?

The answers to those questions can depend on what type—and subtype—you have. Given that lung cancer is the second most common cancer in men and women, arming yourself with knowledge is one of the best things you can do.

What are the different types of lung cancer?

Generally speaking, lung cancer is divided into two categories, non-small cell and small cell lung cancer. (Although there are other types of cancer that can get started in the lungs, including carcinoid tumors and asbestos-related mesothelioma.) Non-small cell is by far the most common, making up 85% of all lung cancers. “The definition is an extremely archaic one, dating back to the earliest days of lung cancer treatment. It was found that if you look at the tumors from these cancers under a microscope, some have small cells and some have bigger cells,” says David P. Carbone, MD, PhD, director of the James Thoracic Center at The Ohio State University in Columbus.

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Non-small cell can be located in the mid-chest, but it’s also often found in other parts of the lung too. Non-small cell lung cancer is further divided into subcategories including adenocarcinomas (which make up about 70% of non-small cell cancers), squamous cell carcinomas, and less common types, including large cell carcinomas, adenosquamous carcinomas, and sarcomatoid carcinomas.

Small cell is typically more centrally located in lungs. “We often see masses in the mid-chest,” adds Nicholas Rohs, MD, attending physician in hematology and oncology at Mount Sinai Downtown-Chelsea Center in New York City.

What are the lung cancer risk factors?

It’s likely you associate lung cancer with smoking, and for good reason. When it comes to non-small cell, the majority are smokers, but 15% to 20% are not. “There are 20,000 patients who get lung cancer who have never touched a cigarette,” says Dr. Carbone.

“Nonsmokers who are diagnosed will come in and say ‘why do I have this’?, but we don’t know,” says Gregory Kalemberian, MD, clinical professor of medicine in hematology/oncology at The University of Michigan in Ann Arbor. Radon and asbestos exposure are other causes, but, as he points out, they’re not terribly common. And it’s still unknown whether there’s a genetic predisposition at play, but he notes that it’s rare that it runs in families.

In small cell lung cancer, 98% of patients are former or current heavy smokers. “If we see it in a non-smoker, we ask ‘are you sure?’ and recheck the pathology reports,” says Dr. Kalemberian. The more “pack years” you smoke (defined as the number of packs smoked per day per year), the greater the risk of small cell, adds Dr. Rohs.

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What are the symptoms of lung cancer?

The symptoms are similar for both non-small cell and small cell cancer: cough, shortness of breath (especially when exerting yourself), fatigue, weight loss, lack of appetite, and rarely, severe chest pain and coughing up blood, explains Dr. Rohs.

The symptoms can be hard to spot in the early stages. He estimates that about 60% of people with non-small cell and three-quarters of people with small cell have an advanced form of cancer when it is diagnosed. Why is that? “For better or worse, we have a lot of lung to give,” Dr. Rohs explains. “Even if you have something growing in your lungs, it may not cause symptoms for a while,” he says. General screening is rarely used, so few early cases are being identified. And symptoms can masquerade as a lot of other problems. They could point to something far less worrisome, like allergies, a virus, or bronchitis. In some cases, they may be attributed to chronic obstructive pulmonary disease, or COPD, which includes emphysema and chronic bronchitis. COPD can also be caused by smoking and is often diagnosed in long-term smokers (although like lung cancer, you don't have to smoke to get COPD).

What is the treatment for non-small cell lung cancer?

Non-small cell lung cancer is less aggressive than small cell, but any type of lung cancer is still “an aggressive cancer that tends to spread and metastasize,” says Dr. Kalemerian. That’s one reason only about 25% of patients come in with early stage (stage 1 or 2), he notes. “That’s a pretty low rate relative to other cancers like breast or colon,” he says.

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When a patient has early stage cancer, surgery to remove the cancer is an option. In later stages of non-small cell cancer, where the cancer has spread to lymph nodes in the chest, treatment is commonly chemotherapy and radiation, according to Dr. Kalemkerian.

In those with adenocarcinomas, the most common type of non-small lung cancer, the tumor may be tested to determine if there are specific mutations in the DNA. If there is, the tumor may better respond to certain targeted oral medications, says Dr. Rohs. The reality of lung cancer treatment today is that technology is moving at such a fast clip, and new drugs are constantly being developed. “We are trying to do personalized medicine based on the patient in front of us and the biology of the tumor,” he says. The benefit is that these oral pills require patients to see the doctor far less (and thus maintain a sense of normalcy), and they’re simply more effective than chemo, adds Dr. Kalemkerian. “They offer better shrinkage and longer control of the disease,” he says.

If the tumor doesn't contain these specific mutations, a patient may still be a candidate for immunotherapy, another targeted therapy that’s been shown to offer a better outcome compared to chemo.

Still, because so much depends on the type and stage of cancer, the prognosis can hard to predict. “I tell my patients that statistics apply to populations, but not patients,” says Dr. Carbone. (Learn more about specific survival rates at the American Cancer Society.) “That doesn’t mean you won’t die in six weeks—or of old age. We try to make everyone above average,” he says.

What is the treatment for small cell lung cancer?

The treatment depends on the type and stage of cancer at diagnosis. In general, the pace of treatment is faster for small cell cancer. These tumors tend to spread more rapidly from the lungs to lymph nodes and other organs in the body. “I’ve seen small cell double in size in two weeks,” says Dr. Kalemkerian, adding that chemo and radiation can put about one-quarter of these people into remission. Doctors may also preventatively treat the brain with radiation, as cancer cells that have metastasized, or spread in the body, may end up here, he notes.

Metastatic cancer is more common with small cell cancer. It will also be treated with chemo and radiation, which can shrink the tumor to half its original size in 60% of patients, says Dr. Kalemerian.

Expert recommendations for lung cancer patients:

Get a second opinion: “Lung cancer is now complicated. It’s no longer just small cell and non-small cell. Just in the last year there have been more than half a dozen new drugs approved. The average doctor may not be up to date on this. I suggest everyone get a second opinion at a major academic medical center before they start therapy,” says Dr. Carbone.

See a specialist: Along the same lines, “even if you want to get treated in a community because the pace and medicine is changing quickly, you want to see someone who knows the most up-to-date information on the specific disease type you have,” says Dr. Rohs. “That’s the one piece of advice I would give to friends and family,” he says.

Get a palliative care specialist involved: Palliative care addresses any medical issues that are not related to the cancer itself, for example, pain and quality of life. These needs may not necessarily be addressed by your doctor. “Early palliative care actually improves quality and quantity of life,” says Dr. Rohs.

Seek out more info: Patients and families should educate themselves to really understand what their doctor is talking about, says Dr. Carbone. He recommends the LUNGevity Foundation and the Bonnie J. Addario Lung Cancer Foundation.