Lung cancer, both small cell and non–small cell, is the second most common cancer in both men and women in the United States, with about 238,340 new cases diagnosed each year, and the leading cause of cancer-related mortality, accounting for more than 127,000 deaths annually.1 Lung cancer in younger adults is relatively rare—approximately 10% of lung cancers are diagnosed in people younger than age 55, and the rates dramatically drop with every preceding decade, down to 1.4% in people younger than age 35.2,3 That said, studies have showed the genomics and clinical characteristics of the disease in younger patients differ from those of older-onset lung cancer.
Survival outcome in these younger patients is also worse, suggesting a more aggressive disease biology, according to a 2016 study by Geoffrey R. Oxnard, MD, FASCO, and his colleagues.4 Dr. Oxnard is a thoracic oncologist at Boston Medical Center and Senior Vice President and Head of Clinical Development at Foundation Medicine.
Geoffrey R. Oxnard, MD, FASCO
“The questions we asked in our study were whether young lung cancer is genomically different compared with older-onset disease, and at what age does a genomic difference become apparent?” said Dr. Oxnard. “We looked at the drivers of alterations that define lung cancer biology and found that some are enriched at a younger age, like ALK, ROS1, and HER2, whereas BRAF was found more often in older patients. Other studies have found age to be associated with lung cancer genomics as well. For example, lung cancer in older patients is enriched for MET exon 14 skipping mutations.”5
According to Dr. Oxnard, changes in the biology of lung cancer start at around age 50, and he considers young-onset lung cancer as being diagnosed before age 40.
Analyzing the Differences Between Young- and Older-Onset Lung Cancer
In an exclusive analysis for The ASCO Post, Komodo Health, a New York City–based data analytics company, looked at differences in clinical presentations, diagnosis, and treatment strategies between younger and older individuals with lung cancer. The results may help shed light on incidence trends in this younger population of patients.
In this analysis, Tabby Khan, MD, MPH, Medical Director of Komodo Health, examined data from ICD-10-CM oncology claim codes stored in Komodo’s Healthcare Map to extract information regarding age at diagnosis; race/ethnicity; gender; smoking status; screening, diagnosis, and treatment; clinical presentation; the top medical specialties evaluating and treating patients by age group; and the time from symptoms and diagnosis to treatment. Because this analysis included ICD-10-CM codes alone, the screening rates included here are likely lower than those seen in real-world settings.
This analysis is based on approximately 518,866 insured Americans—50.4% women and 49.6% men—diagnosed with lung cancer in 2022. As expected, the overwhelming majority of patients, 90.5%, were between the ages of 56 and 88; 8.4% were between the ages of 35 and 55; and 0.9% were between the ages of 18 and 34. Most of the older cohorts, 79%, were current smokers vs 22% in the younger-than-35 cohort. Most patients were White (75.8%); 11.4% were Black; 6.9% were Hispanic or Latino; 3.4% were Asian or Pacific Islander; and 2.4% identified as “other.” A summary of Dr. Khan’s findings is presented here.
Clinical Presentation
Although both younger and older patients experienced common symptoms of lung cancer prior to their diagnosis, including shortness of breath, cough, and chest pain, there were some surprising differences between the two age groups. For example, older patients were more likely to have shortness of breath than younger patients—55% vs 42%, respectively.
“Shortness of breath is a classic lung cancer symptom and is common in older patients. I expect symptomatic older patients to routinely undergo a lung cancer workup, potentially expediting their diagnosis,” explained Dr. Oxnard. “But younger patients may not develop shortness of breath and may not undergo a clinical workup until their next set of symptoms appear. That would be one hypothesis.”
Older patients are also more likely to have other comorbidities that send them to their physician when they have a concern, said Dr. Khan. “People who are younger than age 35 may have a cough and think it’s an allergy, and in that situation, those with less access to health insurance or to a primary care provider may not present to a physician.”
Another unexpected finding is that those aged 35 and younger were more likely than their older counterparts to experience nonspecific symptoms, such as nausea (32% vs 19.8%), fever (42% vs 3.4%), and unspecified abdominal pain (44% vs 31.3%). “Young patients in this analysis probably had a more advanced burden of cancer, which could explain an atypical spectrum of advanced cancer symptoms like abdominal pain or nausea caused by liver metastasis,” said Dr. Oxnard.
Specialties Evaluating Symptoms
Younger patients were more likely to be evaluated for their symptoms in the emergency room than older patients (42% vs 33%), who more often were evaluated by an internal medicine or family medicine practitioner. “Understanding the reason why young adults are receiving their diagnosis in the emergency room is important,” said Dr. Khan. “As mentioned earlier, younger patients usually do not see a physician until they are struggling, possibly because they do not have stable insurance or a regular primary care provider, or because they attribute their problem to allergies or a cold. It’s imperative that we get these younger patients into primary care, so they can have regular checkups and the disease can be found earlier. We also need to educate young people, as well as primary care physicians, about the symptoms of young-onset lung cancer.”
Time From Diagnosis to Treatment
On average, following a diagnosis, younger patients received chemotherapy 10 days sooner and surgery 15 days sooner than patients aged 35 and older, possibly because younger adults are more likely to need aggressive treatment compared with their older counterparts, according to Dr. Oxnard. “It might be that these young patients are presenting with more advanced disease, and we are meeting it with greater clinical urgency compared with older patients, who might be presenting with more incidental disease and lower-burden disease,” said Dr. Oxnard.
Younger patients are also more likely to have fewer comorbidities and can withstand intensive therapy. “We want to be more aggressive with younger patients,” said Dr. Khan. “The younger you are, the fewer comorbidities you have. Older patients are more likely to have chronic obstructive pulmonary disease and hypertension, which puts them at greater risk for complications with anesthesia, so they require a longer medical workup than younger, healthier patients. It is incumbent upon providers to ensure that patients have the appropriate level of care to ensure the best possible outcome.”
We want to be more aggressive with younger patients...It is incumbent upon providers to ensure that patients have the appropriate level of care to ensure the best possible outcome.— Tabby Khan, MD, MPH
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Determining the Causes of Lung Cancer in Young Adults
Although this analysis did not examine vaping or environmental factors, such as exposure to various types of hazardous substances, including outdoor toxic air pollutants, as contributing causes in the development of young-onset lung cancer, according to Dr. Khan, these factors should be investigated.
“Although the insurance claims data in our analysis do not tell the full story of the risk factors involved in young-onset lung cancer, they help identify the problem and provide some understanding about who to target for outreach,” said Dr. Khan. “What is troubling is that while a lot of smoking cessation efforts have focused on replacing tobacco smoking with vaping, most e-cigarettes contain nicotine, which is highly addictive, as well as other substances that can lead to lung injury and potentially lung cancer. We need to do more research in this area to see if there is a correlation between rising trends in young-onset lung cancer and exposure to vaping and air pollution.”
DISCLOSURE: Dr. Oxnard is employed by Foundation Medicine and holds equity in Roche. Dr. Khan is employed by Komodo Health.
REFERENCES
1. American Cancer Society: Key statistics for lung cancer. Available at www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html. Accessed August 16, 2023.
2. De Groot PM, Wu CC, Carter BW, et al: The epidemiology of lung cancer. Transl Lung Cancer Res 7:220-233, 2018.
3. Liu B, Quan X, Xu C, et al: Lung cancer in young adults aged 35 years or younger: A full-scale analysis and review. J Cancer 10:3553-3559, 2019.
4. Sacher AG, Dahlberg SE, Heng J, et al: Association between younger age and targetable genomic alterations and prognosis in non-small cell lung cancer. JAMA Oncol 2:313-320, 2016.
5. Awad MM, Oxnard GR, Jackman DM, et al: MET exon 14 mutations in non-small-cell lung cancer are associated with advanced age and stage-dependent MET genomic amplification and c-MET overexpression. J Clin Oncol 34:721-730, 2016.
