How Small Cell Lung Cancer Is Treated

Treatments for small cell lung cancer can extend life for most limited stage and extended stage tumors. Chemotherapy and radiation therapy is often very effective for a time, but these cancers most often again begin to grow. The addition of immunotherapy combined with chemotherapy for extensive stage disease has led to increased survival after many years of little progress in treatment. Surgery may be effective for a small number of people whose cancers are diagnosed in the earliest stage, and at this stage, may potentially lead to a cure.

Since small cell lung cancer tends to spread early, especially to the brain, radiation to the brain is often used as well. Learn about the different treatment options available so you can work with your doctor to make the best decisions for you as an individual.

The treatment options for small cell lung cancer depend on the stage of the cancer and other factors, such as general health. Fortunately, most of these tumors respond very well initially to treatment, but unfortunately, this improvement does not often last.

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), and include surgery, radiation therapy, and ablation therapies.

Systemic treatments: These therapies treat cancer cells wherever they may be in the body, and include chemotherapy, targeted therapies, and immunotherapy.

Most of the time with small cell lung cancer, cells have spread beyond the original site such that 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 these local therapies such as radiation therapy may reduce symptoms caused by the tumor, and uncommonly with very early stage tumors, surgery may be curative.

General Approaches to Treatment Based on Stage

We will discuss the different types of treatments, but 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, and is usually followed by adjuvant chemotherapy (chemotherapy designed to get rid of any 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 a degree that local treatments cannot control the disease. For decades (and with few advances), a combination of chemotherapy and sometimes radiation therapy were used. Recently, the addition of immunotherapy (a checkpoint inhibitor) to chemotherapy has extended survival, and is now recommended as first-line therapy.

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

Lifestyle

if you smoke (and we realize many people diagnosed with lung cancer have never smoked or quit in the past) smoking cessation important. 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 and 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.

Since smoking cessation can be thought of as a "treatment" for lung cancer (it can extend life and improve quality of life), talk to your oncologist if you find it difficult to stop.

Surgery

Surgery is not commonly used to treat small cell lung cancer but, 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, and 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 (chemotherapy after surgery to clean up any cancer cells that may have spread beyond the tumor but cannot be detected by imaging studies currently available) is usually recommended.

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.)

Chemotherapy

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

Uses

Chemotherapy may be used alone, after surgery with early stage tumors, or in combination with an immunotherapy drug with 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. Studies have found that continuing infusions beyond sex 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 did find 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 metastases to other regions of the body. A test called the systemic immune-inflammation index (SII) has been found to strongly predict prognosis, with people who have a low SII having a significantly longer survival rate than those who have a high SII.

When a cancer progresses or recurs after initial chemotherapy, second-line chemotherapy may be considered (see relapse below).

Radiation Therapy

Radiation therapy may be used in a few different ways to treat the tumor in the chest, and may be used preventively to reduce the risk of metastases in 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 with stage I or stage II limited stage disease that is node negative (and will not be having surgery), stereotactic body radiotherapy (SBRT) is strongly recommended (with chemotherapy before or after the radiation). SBRT is a type of radiation that is given with a "curative" intent and 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)

Since small cell lung cancer tends to spread to the brain relatively early (and is sometimes is the initial symptom), 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 physicians to carefully weigh the risks and benefits. PCI does reduce the risk of small cell lung cancer spreading to the brain (brain metastases), but 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 with extensive stage tumors, however, needs to be weighed against the cognitive changes that are often seen 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 or whole brain radiation to treat brain metastases that are already present, there are options that 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 the radiation to avoid a specific region of the brain important in the formation of memory (the hippocampus) is also thought to limit the damage that leads to cognitive dysfunction. A 2020 study combining the use of Namenda and hippocampal avoidance found that people who received the two therapies had less deterioration in memory and learning ability six months after the radiation than those who did not.

Immunotherapy

Immunotherapy, specifically the class of drugs known as checkpoint inhibitors, have sometimes shown dramatic effects for people with advanced melanoma or small cell lung cancer, but 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 First Line

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 first line may improve overall survival.

In one study (IMpower 133), the immunotherapy drug Tecentriq (atezolizumab) was added to the chemotherapy drugs Paraplatin (carboplatin) and VePesid (etoposide) and 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, and people receiving the combination felt it did not reduce their quality of life.

Responses to Immunotherapy Differ From 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.

Before these drugs begin to work, a tumor may even seem to grow in size on imaging scans. This phenomenon of pseudoprogression with immunotherapy (the appearance on a scan that a cancer is growing even though it is not) can be frightening to people. The reason behind the phenomenon appears to be that immune cells are surrounding a tumor. Since a scan cannot tell the difference between cancer cells and normal cells, the combination of the cancer and surrounding immune cells can make a tumor appear larger. 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 doctor will need to attempt to determine if 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. While it remains the exception, especially with small cell lung cancer, there are some cases in which physicians wonder if a person with stage 4 lung cancer may actually be cured.

Treatment of Relapse and Clinical Trials

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

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

The medication lurbinectedin (an oncogenic transcription inhibitor) was given orphan status and granted priority review after responses were seen in 35% of people with relapsed small cell lung cancer. If it receives approval in August of 2020, it will only be the second drug approved for relapsed disease.

Another potential option includes the drug anlotinib, that appeared to improve progression-free survival.

The immunotherapy drug Opdivo (nivolumab) was approved third line after it was 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 (especially those who do not have brain or liver metastases).

Other options being evaluated include other immunotherapy drugs or combinations, cytokines, cancer vaccines, TLR9 inhibition, and more.

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

Palliative Therapy

Palliative therapy, or therapy designed to improve quality of life but not to cure a cancer or extend life, is 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. Not only does palliative therapy not mean that conventional treatment is abandoned, but 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, and people may need to request a consult. Working with both your oncologist and a palliative care team can be a win-win situation, as it designed to make sure all of your symptoms (emotional and physical) are adequately addressed while freeing up your cancer care team to focus on controlling your cancer.

Scope of Palliative Care

Palliative care teams vary somewhat from cancer center to cancer center but usually include a number of practitioners who can help you cope with issues such as:

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

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, and several cancer centers offer these services.

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

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.

A Word From Verywell

While treatments are often very effective 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.

Was this page helpful?
Article Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Domine M, Moran T, Isla D, et al. SEOM clinical guidelines for the treatment of small-cell lung cancer (SCLC) (2019). Clinical and Translational Oncology. 2020;22(2):245-255. doi:10.1007/s12094-020-02295-w

  2. Eng L, Alton D, Song Y, et al. Awareness of the harms of continued smoking among cancer survivors. Supportive Care in Cancer. 2019. doi:10.1007/s00520-019-05175-4

  3. Peng A, Li G, Xiong M, Xie S, Wang C. Role of surgery in patients with early stage small-cell lung cancer. Cancer Management and Research. 2019;11:7089-7101. doi:10.2147/CMAR.S202283

  4. Zhang C, Li C, Shang X, Lin J, Wang H. Surgery as a potential treatment option for patients with stage III small-cell lung cancer: A propensity score matching analysis. Frontiers in Oncology. 2019;9:1339. doi:10.3389/fonc.2019.01339

  5. Salem A, Mistry H, Hatton M, et al. Association of chemoradiotherapy with outcomes among patients with stage I to II vs stage III small cell lung cancer: Secondary analysis of a randomized clinical trial. JAMA Oncology. 2019;5(3):e185335. doi:10.1001/jamaoncol

  6. Wang C, Jin S, Xu S, Cao S. High systemic immune-inflammation index (SII) represents an unfavorable prognostic factor for small cell lung cancer treated with etoposide and platinum-based bhemotherapy. Lung. 2020;198(2):405-414. doi:10.1007/s00408-020-00333-6

  7. Simone CB, Bogart JA, Cabrera AR, et al. Radiation therapy for small cell lung cancer: An ASTRO clinical practice guideline. Practical Radiation Oncology. 2020. doi:10.1016/j.prro.2020.02.009

  8. Bang A, Kendal WS, Laurie SA, Cook G, MacRae RM. Prophylactic cranial irradiation in extensive stage small cell lung cancer: Outcomes at a comprehensive cancer centre. International Journal of Radiation Oncology Biology and Physics. 2018;101(5):1133-1140. doi:10.1016/j.ijrobp.2018.04.058

  9. Brown PD, Gondi V, Pugh S, et al. Hippocampal avoidance during whole-brain radiotherapy plus memantine for patients with brain metastases: Phase III Trial NRG Oncology CC001. Journal of Clinical Oncology. 2020;38(10):1019-1029. doi:10.1200/JCO.19.02767

  10. Nishio M, Sugawara S, Atagi S, et al. Subgroup analysis of Japanese patients in a phase III study of atezolizumab in extensive-stage small-cell lung cancer (IMpower133). Clinical Lung Cancer. 2019;20(6):469-476.e1. doi:10.1016/j.cllc.2019.07.005

  11. Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019;394(10212):1929-1939. doi:10.1016/S0140-6736(19)32222-6

  12. Mansfield AS, Kazarnowicz A, Karaseva N, et al. Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial. Annals of Oncology. 2020;31(2):310-317. doi:10.1016/j.annonc.2019.10.021

  13. No authors listed. Lurbinectedin is safe and active in relapsed small-cell lung cancer. Cancer Discovery. doi:10.1158/2159-8290.CD-RW2020-053

  14. Yang S, Zhang Z, Wang Q, et al. Emerging therapies for small cell lung cancer. Journal of Hematology and Oncology. 2019;12(1):47. doi:10.1186/s13045-019-0736-3

  15. Armstrong SA, Liu SV. Immune checkpoint inhibitors in small cell lung cancer: A partially realized potential. Advances in Therapy. 2019;36(8):1826-1832. doi:10.1007/s12325-019-01008-2

  16. von Eiff D, Bozorgmehr F, Chung I, et al. Paclitaxel for treatment of advanced small cell lung cancer (SCLC): a retrospective study of 185 patients. Journal of Thoracic Disease. 2020. 12(3):782-793. doi:10.21037/jtd.2019.12.74

  17. Sullivan DR, Chan B, Lapidus JA, et al. Association of early palliative care use with survival and place of ceath among patients with advanced lung cancer receiving care in the Veterans Health Administration. JAMA Oncology. 2019. doi:10.1001/jamaoncol.2019.3105

Additional Reading