Understanding the Treatment Journey in Stage 3 Non-Small Cell Lung Cancer

This article is sponsored by AstraZeneca.

Lung Cancer among People Who Don’t Smoke

Individuals with lung cancer are often assumed to be current or previous cigarette smokers. Smoking is an established risk factor for lung cancer, but this disease can occur among those who have never smoked.¹ In fact, approximately 20,000 to 40,000 Americans who never smoked or smoked fewer than 100 cigarettes over their lifetimes are diagnosed with lung cancer each year. These individuals account for about 10% to 20% of all people who receive a diagnosis of lung cancer in the United States.¹

Several risk factors may contribute to the development of lung cancer among people who do not smoke. In the United States, exposure to radon gas is one common cause, and exposure to secondhand smoke contributes to 2.7% of new cases.^1,2 A family history of lung cancer and genetic mutations can also increase risk of developing the disease.^1,3

“People who never smoked can develop lung cancer,” said Victoria Villaflor, MD, a medical oncologist from the City of Hope Cancer Center in Duarte, CA. “There are screening tests available for patients who smoked but not for patients who never smoked unless there is a familial history. Therefore, it is prudent for a radiologic evaluation to be pursued if a person who did not smoke develops persistent symptoms of cough, chest pain, shortness of breath, coughing up of blood, or weight loss.”

Introduction to Heidi

Heidi never smoked cigarettes, and she developed lung cancer at 55 years of age. A resident of Greenwood Village, Colorado, Heidi lives with her husband and high school sweetheart, Pierre, who is a primary care physician; they have 3 adult children. Heidi has a master’s degree in health education; she has worked as a fitness trainer for 16 years, and has followed a healthy lifestyle. In addition to the physical and emotional challenges associated with the lung cancer diagnosis, Heidi also experienced the social misconceptions people associate with lung cancer. Even family members who she had known for a long time would say, “I didn’t know that you ever smoked.”

Heidi’s Diagnosis

As with many other people, Heidi did not experience any respiratory symptoms before she was given a diagnosis of lung cancer. Because she had a history of ovarian cysts, she visited her gynecologist to determine whether another cyst had developed when she felt a twinge on her lower left side. Results from an ultrasound scan revealed a cyst measuring 6 centimeters on Heidi’s left ovary.

To be thorough, Heidi’s gynecologist also ordered a computerized tomography scan of her chest, abdomen, and pelvis. Results from the scan revealed an abnormal mass in Heidi’s lung. Findings from a positron emission tomography scan and biopsy confirmed that Heidi had a mass located in the upper left lobe of her lung and enlarged lymph nodes in her chest and between her lungs. She was diagnosed with Stage IIIA non-small cell lung cancer (NSCLC), with an adenocarcinoma subtype.

“When I was first given my diagnosis, I couldn’t believe what I was hearing,” Heidi recalled.

Heidi’s pulmonologist advised her to “put her affairs in order,” leading her to believe she didn’t have long to live. She gained a bit of hope when the results of her magnetic resonance imaging scan showed that the cancer had not spread to her brain.

NSCLC Diagnosis and Appropriate Staging

Accounting for 80-85% of all lung cancer diagnoses, NSCLC is the most-common type of lung cancer.⁴ This is caused by cancer cells that form in the tissues of the lung.⁵ Based on the type of cell the cancer has affected, NSCLC is categorized into subtypes.⁶ The most common of these subtypes are adenocarcinoma (40%), or cancer that begins in the cells that line the alveoli (small air spaces in the lung) and make substances such as mucus; followed by squamous cell carcinoma (25%), or cancer that forms in the thin, flat cells lining the inside of the lungs; and large-cell carcinoma (10%), or cancer that may begin in several types of large cells.^5,7

Early detection and treatment of NSCLC is important but may be difficult because symptoms do not always appear early in the disease process.⁸ Symptoms are dependent on several factors including the location of the tumor and how or where it has spread to.⁹ Some symptoms of NSCLC (such as a cough that does not go away) may not be perceived as serious by the individual, which can delay detection.^8,10

“Because lung cancer symptoms—such as cough, chest pain, or wheezing—can be mistaken for a less serious illness,¹⁰ we would encourage an appointment with the doctor and recommend inquiring about radiologic testing,” Villaflor advised. “The earlier lung cancer gets detected, the more options a patient may have for treatment.”⁸

Staging

The stages of NSCLC range from I through IV, and describe the location of the tumor and how extensively NSCLC has spread through the lungs and to other areas of the body.^6,11 Stages III and IV (diagnosed in approximately 40% of people with NSCLC¹¹) describe advanced cancer.¹² In Stage III NSCLC, the cancer is in the lungs but may have also spread into lymph nodes or other structures in the chest.¹³ In Stage IV NSCLC, the cancer has spread away from the lungs, or to another part of the body, such as the liver or other organs, or to the fluid in the areas around the lungs or heart.¹³ The letters A, B, and C are used to describe advancement within each stage (such as, Stages IIIA, IIIB and IIIC).^11,13

The overall 5-year survival rate, or percentage of people alive 5 years after the cancer is diagnosed, is 35% for Stage III NSCLC and 7% for Stage IV disease.⁴ By comparison, the 5-year survival rate for NSCLC that hasn’t spread beyond the lung is 63%.⁴

Treatment Options for Stage 3 NSCLC

It is important for people with Stage III NSCLC to be familiar with treatment options so that they can participate in shared decision-making with their provider and broader health care team.¹⁴ Stages IIIA and IIIB tumors may be difficult or impossible to surgically remove.¹¹ Surgery is usually not an option after the cancer has progressed to Stage IIIC.¹¹ Tumors which cannot be removed by surgery are considered to be “unresectable.” Those with unresectable Stage III NSCLC may be eligible for curative intent treatment (given with the goal of cure).¹⁵

As an initial treatment strategy, people with inoperable Stage III NSCLC often receive treatment with chemoradiation (a combination of chemotherapy and radiation therapy).⁷ These therapies are used to treat NSCLC by either killing the cancer cells or stopping their growth.⁵ Radiation therapy targets cancer cells using high-energy x-rays or another kind of therapeutic energy that can be delivered through a machine.⁵ Receiving radiation therapy and chemotherapy concurrently (during the same time period) may increase time of survival; however, use of concurrent therapies could involve more toxic side effects than receiving the treatments one after another.⁶

After treatment with concurrent chemoradiation, people with inoperable Stage III NSCLC may be eligible to receive immunotherapy.⁵

With available treatment options, certain people with inoperable Stage III NSCLC have the opportunity to be treated with curative intent.¹⁵

“Lung cancer care has advanced over the years,” Villaflor said. “We are lucky that we can now develop treatment plans that are uniquely tailored to each patient.^17,18 For this reason, doctor-patient communication and collaboration is more important than ever when it comes to exploring all treatment options.”

Heidi’s Treatment Journey

Although Heidi didn’t think she would have long to live when she was initially diagnosed, she was hopeful when her oncologist said that her cancer was locally advanced (had not spread to distant regions of her body).

The disease stage and its multiple locations meant that Heidi was not eligible to receive surgical treatment. However, Heidi was eligible for other treatment with curative intent. She would first receive concurrent chemoradiation therapy and if the cancer did not progress, she would then receive immunotherapy infusions every other week for 1 year, as long as she could tolerate them or as long as her disease did not progress.

Heidi’s tumor responded well to concurrent chemoradiation therapy without progression after treatment. Heidi was therefore able to receive immunotherapy.

She continues to live life to the fullest between scan to scan.

Heidi acknowledged that, in addition to her medical team, she had an amazing support system throughout her treatment journey. Pierre played the important role of caregiver and medical advocate. Her children and extended family members helped when they could, and she also received support from her fitness students and clinical pharmacists.

“If I was approached by someone who was newly diagnosed with Stage III lung cancer, I would let them know that there is a lot of hope, that I am living proof,” Heidi said. She also acknowledged that the belief that lung cancer only happens to people who have smoked cigarettes is not true. “Anybody with lungs can get lung cancer,” she said. “It should be nothing to be ashamed of since this cancer does not discriminate. Anyone can get this disease.”

References

1. Lung cancer among people who never smoked. Centers for Disease Control and Prevention. Updated November 9, 2020. Accessed September 20, 2021. https://www.cdc.gov/cancer/lung/nonsmokers/index.htm

2. Cancer facts & figures 2021. American Cancer Society. Accessed September 20, 2021. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2021/cancer-facts-and-figures-2021.pdf

3. What Causes Lung Cancer? American Cancer Society. Accessed September 20, 2021. https://www.cancer.org/cancer/lung-cancer/causes-risks-prevention/what-causes.html

4. Lung cancer - non-small cell: statistics. Cancer.net. Published January 2021. Accessed September 20, 2021. https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics

5. Non-small cell lung cancer treatment (PDQ®)–patient version. National Cancer Institute. Updated August 27, 2021. Accessed September 21, 2021. https://www.cancer.gov/types/lung/patient/non-small-cell-lung-treatment-pdq

6. What Is Lung Cancer? American Cancer Society. Accessed September 20, 2021. https://www.cancer.org/cancer/lung-cancer/about/what-is.html

7. Non-small cell lung cancer treatment (PDQ®)–health professional version. National Cancer Institute. Updated July 12, 2021. Accessed September 20, 2021. https://www.cancer.gov/types/lung/hp/non-small-cell-lung-treatment-pdq#_48565_toc

8. Lung cancer early detection, diagnosis, and staging. American Cancer Society. Revised October 1, 2019. Accessed September 20, 2021. https://www.cancer.org/content/dam/CRC/PDF/Public/8705.00.pdf

9. Lung Cancer. Merck Manual Consumer Version. Revised July 2020. Accessed September 20, 2021. https://www.merckmanuals.com/home/lung-and-airway-disorders/tumors-of-the-lungs/lung-cancer

10. Ellis PM, Vandermeer R. Delays in the diagnosis of lung cancer. J Thorac Dis. 2011;3(3):183-188.

11. Lung Cancer – Non-Small Cell: Stages. Cancer.net. Published May 2020. Accessed September 20, 2021. https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/stages

12. Ramalingam S, Belani C. Systemic chemotherapy for advanced non-small cell lung cancer: recent advances and future directions. Oncologist. 2008;13(suppl 1):5-13. doi:10.1634/theoncologist.13-S1-5

13. Non-Small Cell Lung Cancer Stages. American Cancer Society. Accessed September 20, 2021. https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/staging-nsclc.html

14. Lung Cancer – Non-Small Cell: Types of Treatment. Cancer.net. Published May 2020. Accessed September 20, 2021. https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/types-treatment

15. Non-Small Cell Lung Cancer. NCCN Clinical Practice Guidelines in Oncology. Published October 29, 2021. Accessed November 1, 2021.https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf

16. What is immunotherapy? Cancer Research Institute. Accessed September 21, 2021. https://www.cancerresearch.org/en-us/immunotherapy/what-is-immunotherapy

17. Advances in Lung Cancer Research. National Cancer Institute. Accessed September 21, 2021. https://www.cancer.gov/types/lung/research

18. Joshi E, et al. Precision Medicine in Lung Cancer. Eur Med J. 2020.