Lung cancer in young nonsmokers is on the rise: Uncovering the cause
March 12, 2021
For years, we have watched lung cancer rates drop in the U.S., except in one group: Adults younger than 40 with no history of smoking.
These patients are often diagnosed with aggressive cases of non-small cell lung cancer (NSCLC), similar to many longtime smokers. What is particularly baffling is that most are otherwise healthy. Even at stage III or IV cancer, research suggests patients may still be able to physically perform at 85 percent of baseline – their disease was not highly impacting their daily activities, compared with older patients.
Identifying the lung cancer risks earlier is difficult. There are rarely red-flag symptoms in early-stage lung cancer, and the disease is generally not top-of-mind for young people who have never been smokers. So, when young adults present with persistent respiratory symptoms or noticeable abnormalities on imaging exams, the disease has already advanced to late-stage cancer.
We've known for decades that smoking increases the risk of many types of cancer. More than 90 percent of patients with NSCLC are older people with a history of smoking. If we could eliminate smoking, lung cancer would become a relatively rare cancer.
For patients who’ve never smoked, prevention and early detection strategies are unclear. Just 10 percent of patients with lung cancer are 55 or younger. And approximately 12 percent of patients with lung cancer are never-smokers, according to a December 2020 study by the American Cancer Society.
Despite the small patient population, this upward trend is alarming because we don’t know yet what's causing the increase. UT Southwestern is leading several national studies to seek answers to the mysteries of what causes lung cancer in young nonsmokers and how to treat and potentially avoid the disease.
What causes lung cancer in nonsmokers?
Researchers are working to identify specific genetic mutations and anatomical differences that may predispose a young patient to any type of lung cancer. Young patients with NSCLC appear to have more driver mutations in their tumors – factors that predispose them to developing lung cancer.
However, unlike mutations in colon, breast, and ovarian cancers, lung cancer mutations do not appear to be hereditary in the vast majority of patients.
Unknown drivers may also be increasing risks associated with other types of advanced lung cancer. The death of former "Saved By the Bell" star Dustin Diamond at age 44 suggests certain factors may predispose patients to early development of aggressive small cell lung cancers, which are usually associated with smoking.
Genetics aside, we know that inhaling any unnatural substance is unhealthy for the lungs. Vaping has been shown to cause lung damage that can be fatal, and vaping is linked to an increased risk of COVID-19 infection in young adults. It is unclear whether vaping, smoking marijuana, or inhaling other substances increases the risk of NSCLC in patients who never smoked tobacco products.
Related reading: In addition to tobacco products, what causes lung cancer?
What are the symptoms of lung cancer in nonsmokers?
Lung cancer symptoms – such as persistent cough, chest pain, fever, frequent respiratory infections, or chronic bronchitis – strongly resemble the symptoms of other health conditions. Often, patients don’t develop noticeable symptoms until the disease has progressed to an advanced stage.
According to a large, retrospective study published in 2018 in Clinical Lung Cancer, the average duration from first doctor visit with symptoms to cancer diagnosis in 166 patients was two months – some cases took nearly three years.
The 166 patients with NSCLC in this study were initially treated for other conditions:
- 62 percent for pneumonia and respiratory tract infection
- 13 percent were incidentally found to have suspicious masses after imaging for an unrelated reason, such as after a vehicle accident or sports injury
- 21 percent for vague symptoms such as headache, altered mental state, abdominal pain, and back pain
Those vague symptoms can be caused by metastatic lung cancer – late-stage cancer that spreads to other parts of the body and cannot be surgically resected. In 22 percent of patients diagnosed with NSCLC in this study, the cancer already metastatic at the time of diagnosis.
Younger patients tend to have fewer underlying conditions that require regular doctor visits or imaging. When cancers are found incidentally, it's usually because the patient visited the emergency room for a severe acute illness or trauma. If the imaging expert notices a nodule or mass, they will mention it to the emergency medicine doctor.
Support for young adults facing cancer
At UT Southwestern's Simmons Cancer Center, a group of cancer patients, ages 18-39, have forged connections through the Young Adult Support Program. They get together (virtually during COVID-19) to socialize and share their experiences in a place where "people get it."
Diagnosis and treatment
Advanced diagnostic approaches can confirm whether a patient has lung cancer and help determine the stage of the disease. The doctor may recommend one or a combination of these approaches:
- Imaging: CT scans can show small tumors that X-rays might not detect, and PET scans can help differentiate between healthy tissue and cancer. Your doctor may recommend an MRI or a bone scan to determine whether the cancer has spread.
- Bronchoscopy: An outpatient procedure in which we look for abnormalities in your airways and lungs. It involves using a thin tube with a light and camera (bronchoscope), which is inserted through your nose or mouth, down your throat and into your lungs to look for tumors, infection, and blockages.
- Biopsy: Tissue samples from any detected nodules, masses, or lesions, as well as lymph nodes in the chest
Treatment options will depend on how advanced the cancer is upon diagnosis as well as the patient's overall health and treatment goals. Your doctor will explain the risks and benefits of your treatment options, which may include one or a combination of these therapies:
- Surgery: Removal of the tumor, part of the lung (lobectomy), or an entire lung in cases where the cancer has not spread outside the affected lung. UT Southwestern was an early leader in robotic lobectomy, which generally results in less pain, faster recovery, and less scarring than traditional open surgery.
- Medical treatment:
- Chemotherapy can destroy cancer cells before, after, or in lieu of surgery.
- Immunotherapy boosts the immune system, "training" the body to recognize and eliminate cancer cells. In fact, lung cancer was one of the first cancers to be effectively treated with immunotherapy.
- Targeted therapies "seek and destroy" cancer by targeting specific mutations in cancer cells that aren't found in normal cells.
- Radiation therapy:
- Stereotactic ablative radiation therapy (SABR) points an intense dose of radiation directly at the tumor, destroying it while also reducing damage to surrounding healthy tissue. Given in stronger but fewer doses, this treatment can eliminate early-stage tumors and shrink larger tumors to an operable or more manageable size.
- Brachytherapy may be another option, whereby temporary tubes filled with a radioactive source are placed inside or near the cancer to limit nearby tissue damage.
- Intensity-modulated radiation therapy (IMRT) is an advanced treatment that deploys multiple radiation beans of varying intensities and lengths. These beams conform to the tumor's shape, further reducing damage to healthy tissue.
Systemic treatments such as chemotherapy can affect future reproductive health in young patients with cancer, particularly in women. Patients who might want to have children in the future should talk with their doctor about the fertility-related risks and benefits of their treatment options.
During cancer treatment, emotional support is key. Lung cancer carries a stigma due to its strong association with smoking. Social support is more available for patients with a history of smoking – this population makes up the vast majority of patients with lung cancer. However, young patients who never smoked and developed lung cancer might feel more isolated. Their condition is less common, particularly among their peers.
The Harold C. Simmons Comprehensive Cancer Center at UT Southwestern offers support groups and social events for young adults living with cancer. Held virtually during COVID-19, these meetups give patients a safe, welcoming outlet to discuss the unique challenges cancer can bring to family life, relationships, work, school, and more. To get involved, email us at email@example.com.
SABR approach delivers precision cancer care
UT Southwestern's Dr. Robert Timmerman is a nationally recognized expert in the use of SABR, a precise radiation technique that targets and shrinks tumors – and sometimes destroys them – all while damaging very little of the surrounding tissue.
Looking toward the future
Broadening the age range for lung cancer screenings
In March 2021, the U.S. Preventive Task Force updated its lung cancer screening guidelines, which now recommend low-dose CT lung cancer screening for patients age 50 to 80 with a history of heavy smoking (the previous minimum age was 55). The expanded age bracket will open screening to more high-risk patients, potentially catching more lung cancer earlier, when it is more treatable.
Screening means routinely checking high-risk patients for cancer, even if they have no symptoms. Since young adults are such a small percentage of patients with lung cancer, and since we do not yet know what factors may increase a patient's cancer risk, it is not yet possible to screen only high-risk, young patients.
But screening everyone of any risk level, also called over-screening, can do more harm than good. Over-screening can lead to:
- Stress and anxiety after a mysterious mass or nodule turns out to be benign
- Expensive follow-up imaging
- Unnecessary biopsies or bronchoscopies that present risks such as scarring and infection.
However, if further research can help us identify the cause of lung cancer in young nonsmokers, we can potentially determine who is most at risk. From there, we can develop a safe, cost-effective protocol to identify and screen that patient population only.
Internationally, dozens of institutions are working to uncover the mechanisms behind NSCLC in young adults. Here in Dallas, John Minna, M.D., and his research team at the UT Southwestern Hamon Center for Therapeutic Oncology Research are key in furthering our understanding of this disease.
Dr. Minna leads a joint Lung Cancer NCI Special Program of Research Excellence (SPORE) grant between UT Southwestern and MD Anderson Cancer Center to conduct ongoing research into the biology of lung cancer to seek more effective and personalized treatment options.
We currently have over two dozen ongoing lung cancer trials at UT Southwestern, including:
- JoLT-Ca/STABLEMATES: This randomized phase III study will compare outcomes for sublobar resection and SABR in patients with stage I NSCLC.
- Targeting Metabolic Vulnerabilities in Lung Cancer: The goal of this project is to enhance our ability to capitalize on metabolic reprogramming and improve cancer treatment, with a focus on how tumors use lactate as fuel or expel it into their surrounding environment.
- Targeting Immune Vulnerabilities in Lung Cancer Vulnerabilities in Immunologically-Inert Lung Cancer: PD-1/PD-L1 are proteins found in the body's cells. When they bind together, they can "hide" cancer cells from the body's immune system. Most patients with NSCLC do not respond well to immunotherapies that target PD-1/PD-L1. The goal of this study is to find an effective alternative therapy for these patients.
Developing lung cancer despite never smoking is a tragic situation we hope to one day mitigate through personalized medicine. As we learn more about the nuances of lung cancer, and potential key drivers beyond smoking, we can develop more targeted screenings and treatment options to protect patients' respiratory health.