Background
Metastatic non-small cell lung cancer, often abbreviated mNSCLC, is the most advanced stage of a disease that already accounts for a large share of lung cancer deaths. In recent years, care for this cancer has changed dramatically. Treatments such as immune checkpoint inhibitors, molecularly targeted therapies, and more refined chemotherapy regimens have improved survival for many patients and are often better tolerated than older approaches.
Even so, little has been known about how often older adults in the United States actually receive systemic treatment in routine practice. This matters because most people diagnosed with metastatic lung cancer are older, and real-world treatment patterns can differ from clinical trial results. Clinical trials often enroll healthier patients, while everyday practice includes patients with frailty, multiple chronic illnesses, cognitive or social barriers, and rapidly declining health.
This study examined treatment rates among older adults with metastatic NSCLC using a large population-based dataset, with the goal of understanding who gets treated, who does not, and how those patterns have changed over time.
Study design and data source
Researchers used linked Surveillance, Epidemiology, and End Results (SEER) cancer registry data and Medicare claims. This combination is especially useful for population research because it captures both cancer diagnosis information and actual billed medical services for older adults covered by Medicare.
The study included patients aged 65 years and older who were diagnosed with metastatic NSCLC between January 2006 and December 2021. The analysis looked at whether patients ever received systemic treatment, meaning treatment that travels through the body rather than being limited to one site. In lung cancer, this typically includes chemotherapy, immunotherapy, targeted therapy, or combinations of these.
The investigators also examined factors that might influence treatment, including:
– Age
– Sex
– Race and ethnicity
– Marital status
– Comorbidity burden
– Histologic subtype of the cancer
– Rural versus urban residence
– Medicare coverage type
– Referral to an oncology specialist
– Biomarker testing
To account for the fact that some patients die before treatment can even begin, the study used a competing risk model. This is important in metastatic lung cancer because death itself can prevent treatment from ever occurring and can distort simpler analyses.
Who was included
The cohort included 254,611 older adults with metastatic NSCLC. The median age was 73 years, with an interquartile range of 68 to 80 years. Slightly more than half were male.
By race and ethnicity, the cohort was predominantly White, with smaller proportions of Black, Asian, Hispanic, and other or unknown groups. This distribution reflects the underlying population captured in the registry and Medicare data.
A striking feature of the cohort was how quickly many patients died after diagnosis. About 39.8% died within 90 days of being diagnosed. This short survival time helps explain why treatment rates are so challenging in metastatic lung cancer: some patients are diagnosed very late, have rapidly progressive disease, or are too ill to begin therapy.
Main findings
Overall, 46.8% of patients ever received systemic treatment. In other words, slightly less than half of older adults with metastatic NSCLC received any body-wide anticancer therapy at all.
Among patients who died within 90 days of diagnosis, only 13.2% were treated. By contrast, 69% of those who survived longer than 90 days received treatment. This difference highlights a major clinical reality: the sickest patients are often unable to start therapy before their condition worsens further.
Treatment rates improved only slightly between 2006 and 2021, despite major advances in available therapies over that period. That finding is especially notable. One might expect rising treatment use as immunotherapy and targeted drugs became more effective and sometimes less toxic than older chemotherapy. Instead, the proportion treated barely moved, suggesting that advances in science did not fully translate into population-level care.
Factors linked to higher or lower treatment rates
Several factors were associated with the chance of receiving treatment.
Referral to an oncology specialist had one of the strongest associations with treatment. Patients who were referred were much more likely to receive systemic therapy. In the competing risk model, the hazard ratio was 2.5, meaning referral was associated with a substantially higher likelihood of treatment over time. At 180 days, this translated into a 30.3% greater cumulative incidence of treatment compared with patients who were not referred.
This is clinically important. It suggests that access to specialist evaluation may be a major gateway to treatment. When patients are not seen by oncology early enough, opportunities for biomarker testing, treatment discussion, and shared decision-making may be lost.
Biomarker testing also mattered. Patients who underwent biomarker testing had a 17.8% greater cumulative incidence of treatment at 180 days. This makes sense because biomarker testing is now essential in metastatic NSCLC. It identifies tumor features that may open the door to targeted therapies or immunotherapy. Common biomarkers include EGFR mutations, ALK and ROS1 rearrangements, BRAF mutations, MET exon 14 skipping, RET and NTRK alterations, and PD-L1 expression.
Age strongly influenced treatment. Patients older than 80 years had a 15.4% lower cumulative incidence of treatment at 180 days compared with those aged 65 to 69 years. This is not surprising, but it raises important concerns. Some of the difference likely reflects legitimate medical issues such as frailty, impaired organ function, or patient preference. However, it may also reflect undertreatment based on age alone.
Cancer histology mattered as well. Patients whose NSCLC was classified as not otherwise specified had a 12.8% lower cumulative incidence of treatment than patients with adenocarcinoma. This may reflect incomplete diagnostic workup, difficulty obtaining adequate tissue, or fewer chances to identify targetable abnormalities.
Other factors linked to treatment differences included:
– Comorbidity burden
– Marital status
– Medicare Part C or Part D coverage
– Rural residence
– Race and ethnicity
These differences point to both clinical and social determinants of care. They suggest that insurance coverage, geography, social support, and structural inequities may all shape whether a patient receives treatment.
Why this study matters
This study shows that, even in an era of rapid therapeutic progress, many older adults with metastatic NSCLC never receive systemic therapy. That is a sobering finding because modern treatment can sometimes improve both survival and quality of life.
At the same time, it would be too simplistic to say every patient should receive treatment. Metastatic lung cancer is often aggressive, and some patients are too ill to benefit. For some, the burdens of treatment may outweigh the likely gains. The key issue is not that every patient must be treated, but that every patient should have an informed, timely opportunity to be evaluated for treatment when appropriate.
The very low treatment rate among patients who died within 90 days suggests that diagnosis often occurs late in the disease course, when the window for therapy is already closing. Earlier detection, faster referral, and streamlined biomarker testing may help more patients receive potentially beneficial care.
Clinical implications
The findings suggest several practical steps for improving care:
1. Earlier specialist referral
Primary care clinicians, emergency physicians, hospitalists, and pulmonologists should refer patients with suspected advanced lung cancer to oncology promptly, especially when treatment decisions need to be made quickly.
2. Rapid biomarker testing
Molecular testing and PD-L1 testing should be integrated early in the workup of metastatic NSCLC. Delays in testing can delay or prevent access to targeted or immunotherapy-based treatment.
3. Attention to frailty and goals of care
Older adults should be assessed individually rather than by age alone. Functional status, symptoms, cognition, nutrition, social support, and patient goals all affect whether systemic therapy is reasonable.
4. Support for patients with social barriers
Transportation, rural access, insurance coverage, language barriers, and caregiver availability can affect treatment initiation. Addressing these issues may help reduce disparities.
5. Better care coordination
Because metastatic lung cancer progresses quickly, systems that speed diagnosis, biopsy, pathology review, biomarker analysis, and oncology consultation are likely to improve access to treatment.
What systemic treatment usually means in metastatic NSCLC
Systemic therapy for metastatic NSCLC is not a single treatment. It is a category that includes several approaches:
– Chemotherapy, which attacks rapidly dividing cells
– Immunotherapy, which helps the immune system recognize and attack cancer cells
– Targeted therapy, which blocks specific genetic changes that drive tumor growth
– Combination regimens, which may pair chemotherapy with immunotherapy or use other tailored approaches
The best option depends on tumor biology, PD-L1 status, specific gene alterations, symptom burden, and the patient’s overall condition. In some patients with actionable mutations, targeted therapy can be especially effective and may be better tolerated than conventional chemotherapy.
Limitations to keep in mind
Because this was an observational study, it can show associations but cannot prove why treatment did or did not occur. Some potentially important details are also not fully captured in claims data, such as patient preferences, frailty measures, performance status, smoking history, or exact reasons a clinician chose not to treat.
In addition, Medicare claims can identify whether services were billed, but they do not always reveal the complete clinical context. For example, a patient might decline therapy, might receive care outside the captured system, or might be deemed medically inappropriate for treatment because of very limited life expectancy.
Even with these limitations, the study offers a highly informative picture of real-world care in a large and diverse population.
Bottom line
Among older adults with metastatic NSCLC, fewer than half ever received systemic treatment, and treatment rates improved only slightly from 2006 through 2021. Referral to oncology and biomarker testing were strongly linked to treatment, while advanced age, certain histologic findings, and social or insurance-related factors were associated with lower treatment rates.
The study suggests that major progress in lung cancer therapy has not yet fully reached many older adults in everyday practice. Improving early specialist access, speeding biomarker testing, and addressing barriers to care may help ensure that more patients who could benefit from systemic therapy actually receive it.
