How Small Cell Lung Cancer Is Treated

Treatments for small cell lung cancer can extend life for most limited-stage and extended-stage tumors. The options depend on the stage of the cancer and other factors, such as general health.

This article discusses the different treatments available, including chemotherapy, immunotherapy, surgery, and radiation therapy. It also covers therapies that help people deal with symptoms, including palliative care and complementary medicine.

Types of Treatment

Treatments for cancer can be broken down into two major categories: local and systemic.

• Local treatments: These therapies treat cancer where it originates (or isolated areas where it spreads). They include surgery and radiation therapy.
• Systemic treatments: These therapies treat cancer cells wherever they may be in the body. They include chemotherapy, targeted therapies, and immunotherapy.

Most of the time, when small cell lung cancer is discovered, cells have already spread beyond the original site. Therefore, local therapies are ineffective in getting rid of all of the cancer. For this reason, systemic therapies are the mainstay for most small cell lung cancers.

That said, even with advanced disease, local therapies (such as radiation therapy) may reduce symptoms caused by the tumor. With very early-stage tumors, surgery may be curative.

Treatment Based on Stage

Before discussing the different types of treatments, it can be helpful to discuss the general approaches based on stage.

Limited-stage: With limited-stage small cell lung cancer, there is a potential for curing the disease. With very early tumors, surgery may be considered. It's usually followed by adjuvant chemotherapy. This is designed to get rid of any remaining cancer cells that may have spread but can't be detected on imaging.

Stereotactic body radiotherapy (SBRT) is a type of specialized radiation therapy that may be used as an alternative. Otherwise, combination chemotherapy and radiation therapy are usually given.

Extensive-stage: By definition, extensive-stage small cell lung cancers have spread to the degree that local treatments cannot control the disease. For decades (and with few advances), a combination of chemotherapy and sometimes radiation therapy was used.

Recently, the addition of immunotherapy to chemotherapy has extended survival. It's now recommended as first-line therapy. This includes therapies such as Imfinzi (durvalumab), in combination with Imjudo (tremelimumab), and platinum-based chemotherapy.

Second-line therapy: For cancers that relapse or progress after treatment, the chemotherapy drug Hycamtin (topotecan) has been the standard of care. Other options (sometimes via clinical trials) may include repeating chemotherapy and using newer drugs such as Zepzelca (lurbinectedin) or other immunotherapy drugs.

Prescriptions

Your healthcare provider may prescribe systemic treatment such as chemotherapy or immunotherapy. Chemotherapy uses drugs to kill cancer cells or stop them from dividing. It's either taken by mouth or injected into the body so the drug can enter your bloodstream.

In immunotherapy, your body's immune system is activated to kill the cancer cells. The treatment uses substances that are made by your body or in a lab to boost your body's natural defenses against cancer cells.

Chemotherapy

Chemotherapy is recommended for most people with small cell lung cancer (with or without immunotherapy). It improves survival for both limited-stage and extensive-stage disease.

Uses

Chemotherapy may be used alone, after surgery for early-stage tumors, or in combination with an immunotherapy drug for advanced-stage cancers. It may also be combined with radiation therapy either to the chest or the brain.

Medications

First-line treatment of small cell lung cancer usually involves the use of two drugs (combination chemotherapy):

• A platinum drug, such as Platinol (cisplatin) or Paraplatin (carboplatin)
• VePesid (etoposide)

Sometimes the drug Camptosar (irinotecan) may be used instead of VePesid.

Length of Treatment

Chemotherapy is usually given in a series of four to six infusions or injections. Studies have found that continuing infusions beyond six does not appear to improve outcomes, but does increase side effects. (Radiation may be used at the same time, often once or twice daily.)

Prognosis with Chemotherapy

Small cell lung cancer usually responds well to chemotherapy initially, but the response is often short-lived. Even with earlier stages (limited-stage) disease, chemotherapy does not often "cure" these cancers.

That said, a 2019 study found that the combination of chemotherapy and radiation did result in long-term survival for some people with limited-stage small cell lung cancer.

Some people respond better to chemotherapy than others. Factors that are associated with poorer survival include a history of smoking, a more advanced tumor stage, and a larger number of tumors that spread to other regions of the body.

A test called the systemic immune-inflammation index (SII) has been found to strongly predict prognosis. People who have a low SII have a significantly longer survival rate than those who have a high SII.

When cancer progresses or recurs after initial chemotherapy, second-line chemotherapy may be considered.

Immunotherapy

Immunotherapy, specifically the class of drugs known as checkpoint inhibitors, has sometimes shown dramatic effects for people with advanced melanoma or small cell lung cancer. Until recently, their role in treating small cell lung cancer was limited. That is now changing, and the use of these drugs is now recommended first-line for extensive-stage tumors.

Effectiveness As First-Line Treatment

After three decades during which no significant advances were made that resulted in increased survival with small cell lung cancer, two separate clinical trials have found that combining immunotherapy with chemotherapy as first-line treatment may improve overall survival.

In one study (IMpower 133), the immunotherapy drug Tecentriq (atezolizumab) was added to the chemotherapy drugs Paraplatin and VePesid. This was found to improve both progression-free and overall survival relative to chemotherapy alone.

In the other study (CASPIAN), combining the immunotherapy Imfinzi (durvalumab) with the chemotherapy drugs (a platinum drug plus VePesid) similarly showed significantly improved survival.

The drug Opdivo (nivolumab) is approved for people who have received at least two previous lines of therapy.

Side Effects

Side effects of checkpoint inhibitors differ from those commonly seen with chemotherapy and can include inflammation (of the skin, lungs, or other regions) as well as endocrine problems (such as hypothyroidism).

Fortunately, in a 2020 study looking at Tecentriq combined with chemotherapy, the combination of treatments resulted in no more side effects than chemotherapy alone. People receiving the combination felt it did not reduce their quality of life.

Responses to Immunotherapy Compared to Other Treatments

The response patterns to immunotherapy are different than those seen with chemotherapy and other therapies, and this can be very confusing.

Unlike chemotherapy, which works almost immediately due to the drugs causing cell death, immunotherapy can take some time to be effective. Checkpoint inhibitors work in a way that is analogous to taking the brakes off of the immune system.

Our immune systems know how to fight cancer, but cancer cells often find ways to "hide" from the immune system. By taking the mask or disguise off of cancer cells, the immune system can do its job of going after and attacking cancer cells. This process, however, takes time.

Metastases that were not seen before may also be seen (or appear to arise anew) due to this phenomenon.

Uncommonly, immunotherapy may sometimes result in a paradoxical effect and more rapid growth of a tumor (hyperprogression with immunotherapy). If your tumor seems to grow on immunotherapy, your healthcare provider will help determine why. They'll look into whether it is pseudoprogression, if the medication is simply not working, or if hyperprogression is present.

An exciting phenomenon that is not unique (but is much more common) with immunotherapy is what is referred to as a durable response. There is not a precise definition at this time, but this is essentially a long-term response to the drugs that may even continue after the drugs are stopped.

It remains the exception, especially with small cell lung cancer. However, there are some cases in which healthcare providers wonder if a person with stage 4 lung cancer may actually be cured.

Medications for Relapses

When small cell lung cancer relapses, there are relatively few effective medications for treatment. However, there are clinical trials in place looking at other options either alone or combined with current treatments.

One FDA-approved second-line therapy is Hycamtin, although only a minority of people (around 16%) will respond.

The medication lurbinectedin (an oncogenic transcription inhibitor) was given orphan status by the U.S Food and Drug Administration in 2018. This status means it showed promise for treating a rare life-threatening condition.

Lurbinectedin was granted priority review after responses were seen in 35% of people with relapsed small cell lung cancer. It received accelerated FDA approval in June 2020 to become the second drug approved for relapsed disease.

Anlotinib, an oral tyrosine kinase inhibitor, has been shown to improve progression-free survival in patients with advanced small cell lung cancer that progressed after prior treatment. As of November 2022, anlotinib was not yet FDA approved.

The immunotherapy drug Opdivo (nivolumab) was approved third line, meaning when the first and second lines of therapy aren't working. It's been found to have a response rate of almost 12% and a median duration of response of nearly 18 months.

The chemotherapy drug Taxol (paclitaxel) also appears to be helpful for some people who have already received extensive treatment for small cell lung cancer. This is especially the case when the cancer hasn't spread to the brain or liver.

Other options being evaluated include other immunotherapy drugs or combinations, cytokines (proteins that control immune system activity), cancer vaccines, and more.

Unlike non-small cell lung cancer, targeted therapies (drugs that target specific molecular abnormalities in the cancer cells) now have little role in treatment. However, they may with further research and understanding of the genetic profile of small cell lung cancer in the future.

Surgeries and Specialist-Driven Procedures

In some cases, your healthcare provider may recommend radiation therapy or surgery. These procedures are usually performed along with another treatment like chemotherapy.

Radiation therapy delivers high-energy x-rays or other radiation to fight cancer cells. Surgery is used if the cancer is only found in one lung. Usually, this type of cancer is found in both lungs, so surgery is often not the only treatment.

Radiation Therapy

Radiation therapy may be used in a few different ways to treat the tumor in the chest. It can also be used preventively to reduce the risk of metastasis (spreading) to the brain.

Chest Radiation

Whether radiation therapy to the chest is recommended or not depends on other treatments used and the stage of the disease. Fortunately, the American Society of Radiation Oncology has put forth guidelines that can help with decision-making.

When surgery will be performed for limited-stage disease, radiation therapy should follow for those who have positive lymph nodes or positive margins (when the cancer extends to the edges of the tissue removed during surgery).

For people not having surgery with stage I or II limited-stage disease that is node-negative, stereotactic body radiotherapy (SBRT) is strongly recommended. Chemotherapy is given before or after the radiation.

SBRT is a type of radiation that is given with a "curative" intent. It involves using a high dose of radiation to a very localized area of tissue. In some cases, the results of surgery and SBRT can be similar.

When chemotherapy will be used for limited-stage tumors, once- or twice-daily radiation therapy is usually recommended early in the course of treatment.

With extensive-stage small cell lung cancer, radiation therapy may be used for some people after chemotherapy or for those who are responding to the combination of chemotherapy and immunotherapy.

In some situations, proton beam therapy may be recommended as an alternative to external beam radiation. Proton beam therapy works in a similar way to conventional radiation, but some researchers believe it results in less damage to nearby healthy tissue.

Prophylactic Cranial Irradiation (PCI)

Small cell lung cancer tends to spread to the brain relatively early and is sometimes the initial symptom. Therefore, preventive whole-brain radiation is often used. Unfortunately, due to a tight network of capillaries called the blood-brain barrier, most chemotherapy drugs are unable to enter the brain.

The decision to use prophylactic cranial irradiation (PCI) requires patients and their healthcare providers to carefully weigh the risks and benefits. PCI does reduce the risk of small cell lung cancer spreading to the brain (brain metastases). However, it can cause significant cognitive problems (such as problems with memory, concentration, and more) for many people.

PCI is currently recommended for people with stage II or stage III limited-stage small cell lung cancer who respond to chemotherapy. (It is not recommended for very small, stage I limited-stage tumors.)

With extensive-stage small cell lung cancer, PCI is most often recommended for those who have at least a partial response to chemotherapy or chemoimmunotherapy. In this setting (when a cancer is responding), PCI appears to improve survival and delays the time until brain metastases occur.

The benefit of extensive-stage tumors needs to be weighed against the cognitive changes that can significantly reduce quality of life. For this reason, there is currently a debate over using PCI versus periodically monitoring people for brain metastases with brain MRIs.

Reducing Cognitive Problems Related to Whole-Brain Radiation

If you will be receiving PCI to treat brain metastases that are already present, some options may reduce cognitive changes. The medication Namenda (memantine) has been found to reduce cognitive problems when started along with radiation to the brain.

In addition, designing radiation to avoid the hippocampus, the part of the brain that helps form memory, may limit damage leading to cognitive dysfunction. A 2020 study combined the use of Namenda and hippocampal avoidance. It found that people who received the two therapies had less deterioration in memory and learning ability six months after the radiation than those who didn't.

Surgery

Surgery is not commonly used to treat small cell lung cancer. However, for around 5% of people, it may be an option.

When Surgery May Be Considered

Surgery may be considered for some people with limited-stage small cell lung cancer if a tumor is present in only one lung and has not spread to lymph nodes (T1 or T2 and N0). A 2019 study suggests that surgery leads to better survival rates with early-stage small cell lung cancer than non-surgical options.

Some people, however, with more advanced limited-stage tumors (stage III) may benefit from surgery as well. A 2019 study found that for some people with stage III, surgery may improve survival.

When surgery is performed for small cell lung cancer, chemotherapy is usually recommended. Chemotherapy after surgery cleans up any cancer cells that may have spread beyond the tumor but cannot be detected by imaging studies currently available.

The most commonly recommended procedure is a lobectomy or removal of one of the lobes of the lungs. (The right lung has three lobes and the left has two.)

Lifestyle

Many people diagnosed with lung cancer have never smoked or have quit in the past. However, if you do smoke, it's important to quit.

Unfortunately, there is a common misconception that once you've been diagnosed with cancer, especially small cell lung cancer, it's too late to quit. That's simply not the case. The advantages of quitting include both a better response to treatment and a better quality of life.

A 2019 study looked at awareness of the harms of continued smoking among people with cancer. It was found that a significant percentage of people were unaware that continued smoking was associated with:

• Decreased effectiveness of chemotherapy and radiation therapy
• Decreased quality of life during chemotherapy
• Increased side effects due to radiation therapy
• Increased complications when surgery is performed
• Increased risk of death

Smoking cessation can be thought of as a treatment for lung cancer since it can extend life and improve quality of life. Talk to your oncologist if you find it difficult to stop.

Palliative Therapy

Palliative therapy is designed to improve quality of life but not to cure a cancer or extend life. It's important for everyone with advanced cancer.

Palliative Therapy Differs From Hospice

Palliative therapy differs from hospice in that palliative care can be used even by people who have early-stage, highly curable cancers. Palliative therapy does not mean that conventional treatment is abandoned. In fact, according to a 2019 study, people with advanced lung cancer who received palliative care actually lived longer.

Despite the benefits, the addition of palliative care to cancer care is still relatively new. You may need to request a consult.

Working with both your oncologist and a palliative care team can be a win-win situation. It's designed so your physical and emotional symptoms are addressed while freeing up your cancer care team to focus on controlling your cancer.

Scope of Palliative Care

Palliative care teams vary somewhat depending on the cancer center. Typically, they include a number of practitioners who can help you cope with issues such as:

• Pain
• Side effects of cancer growth (this may include treatments such as stent placement to keep a blocked airway open)
• Shortness of breath
• Nutritional management for weight loss and eating difficulties
• Emotional distress
• Family concerns related to your cancer

Complementary and Alternative Medicine

At the current time, there are no alternative or complementary therapies that are effective for treating small cell lung cancer. That said, some of these therapies may help people cope with the physical symptoms and emotional upheaval caused by cancer. Several cancer centers offer these services.

Examples of mind-body practices that may help with cancer symptoms (such as fatigue, cognitive problems, pain, anxiety, and depression) include:

• Meditation
• Yoga
• Qigong
• Music therapy
• Art therapy
• Pet therapy
• Massage
• Acupuncture

Other activities, such as journaling, can also be helpful, especially when you are trying to figure out how you really feel and what you really need.

Summary

Treatment for small cell lung cancer can be local or systemic. Local means the cancer is treated in isolated areas. Systemic therapies treat cancer anywhere in the body.

When small cell lung cancer is limited, surgery may be considered. In its earliest stage, this can potentially lead to a cure. Extensive-stage small cell lung cancers often require a combination of chemotherapy and radiation therapy or a combination of immunotherapy and chemotherapy to help control the cancer's growth.

Palliative therapy is designed to improve quality of life by addressing issues like pain, emotional distress, and nutrition management. Complementary and alternative medicine practices such as mediation, yoga, and art therapy may help in relieving symptoms like fatigue, anxiety, and depression.

Your healthcare provider will work with you to help you make the best decisions for your particular case.

A Word From Verywell

While treatments are often very effective in the short term for small cell lung cancer, most of these cancers eventually progress. Fortunately, after decades of little progress in treatment, the addition of immunotherapy is extending life, and further treatments are being evaluated in clinical trials.

As treatments advance, so do the options, and it can be confusing trying to decide what is best for you as an individual. Taking some time to research your cancer, asking a lot of questions, and participating in a support community may all help you feel that you have at least some control in a situation that can sometimes feel completely beyond your control.