Early Routine Lung Cancer Screening Leads to Improved Treatment Options and Survival

Key Takeaway

• Patients with a history of screening were significantly more likely to be diagnosed at stages 0 to 2 than those without a screening history.

Introduction

Lung cancer is the leading cause of cancer-related deaths in the United States for both men and women, and it is the second most common cancer diagnosed. Although survival has improved in other cancers, that trend has not been seen with lung cancer. ¹ Survival for all types of lung cancer at 5 years is approximately 23%. ² This is believed to be due to late stage at diagnosis, advanced stage when ultimately symptomatic, and overall lack of screening compliance. In 2011, the National Comprehensive Cancer Network (NCCN) developed screening guidelines to help diagnosis lung cancer at earlier stages by screening those with high-risk features with low dose chest computerized tomography (CT). ¹ According to National Institutes of Health (NIH), 4.5% of adults aged 55 to 80 years at risk for lung cancer due to smoking had a CT scan to screen for lung cancer. ³ In stark contrast, 75.9% of women aged 50 to 74 years had a mammogram to screen for breast cancer, and 71.8 % of adults aged 50 to 75 years had received colorectal cancer screening.^4,5 The National Lung Cancer Screening trial demonstrated that screening improves lung cancer suvival. ⁶ With only 4.5% of eligible individuals being screened, the United States Preventive Services Task Force (USPSTF) recently revised guidelines for lung cancer screening from age 55 years to 50 years and from a smoking history of 30 pack years to 20 pack years. ³ This increases the number of eligible persons who would benefit from screening. Due to this change in eligibility, the NIH set a healthy people 2030 screening target goal of 7.5%. ³

The recommended method of screening for lung cancer is an annual low dose (non-contrast) CT scan. The adoption of CT as a screening method has been poor, with only a small percentage of the eligible population reporting to have had received screening. Multiple factors are believed to contribute to this low percentage including patient hesitancy, the complexity of the guidelines, and multileveled factors that negatively influence the implementation in health systems (lack of health care infrastructure). ⁷ Some patients avoid screening because they fear the results, or out of guilt. The lack of trust among current smoker is brought on by fatigue from smoking cessation conversations and the feeling that the patient brought the diagnosis on independently by smoking. ⁷ Patient trust and guilt remain an ongoing challenge. Furthermore, eligibility can be confusing because guidelines change frequently, and different organizations have different recommendations. For example, the most recent update by the USPSTF was 2021, but the American Cancer Society recently updated its guidelines in November of 2023 and eliminated the requirement of having quit smoking within 15 years. Still another constraining factor is lack of health care infrastructure necessary for screening, which is especially evident in rural settings. ⁷

Treatment for lung cancer varies by stage and if the tumor is considered resectable. Treatment approaches also vary for non-small cell lung cancers vs small cell lung cancers. The most common treatment method for early stage (stages 1-2) resectable non-small cell lung cancers is surgery, which offers the best survival. ⁸ For late-stage cancers (stages 3-4) deemed unresectable, systemic therapy (which includes chemotherapy and immunotherapy) is the mainstay of treatment with possible radiation. Small cell lung cancers are initially more responsive to systemic therapy and radiation but, given its aggressive nature, it is very difficult to treat, regardless of stage. ⁸ Small cell lung cancer treatment depends on histology, but a combination of systemic therapy, radiation, and surgery is included in the treatment algorithm.

Given patient reluctance and lack of trust, ever-changing guidelines, and infrastructure challenges as barriers to lung cancer screening, screening remains low. The goal of this study was to determine whether screening was of benefit in our patient population and, if so, to encourage patient demand and provider recommendation for screening. We hypothesized that lung cancers diagnosed on screening CTs would be found at an earlier stage, thus broadening treatment options and improving overall survival in our rural patient population.

Methods

Following approval of the study, we queried our organization’s electronic health record (EHR) system to identify all patients with a lung cancer diagnosed from 2017 through 2020. Our health system serves a large rural population. We retrospectively reviewed these patients’ EHRs to capture demographic data, lung cancer screening history, and tumor characteristics and treatment information. Pearson χ², Fisher exact, and Wilcoxon rank-sum tests were used to compare demographics, tumor, and treatments of patients with and without screening history. The same tests were applied to assess associations between treatments and stage of cancer at diagnosis. Kaplan-Maier curves with associated log rank test were used to compare survival rates based on screening history and treatments. These curves were used to estimate 3-year overall survival rates. All analyses were conducted using SAS statistical software version 9.4 (SAS institute). All statistical testing used a significance level of .05.

Results

Demographic Characteristics

764 patients had lung cancer diagnoses in our health system from 2017 through 2020. At diagnosis, the average age was 69.7 ± 10.1 years, and average body mass index (BMI) at diagnosis was 28.1 ± 7.0 kg/m². The study cohort was 45.3% female and 98.3 % White. Within this cohort, 14.7% (112/764) had a history of lung cancer screening and 10.2% (78/764) had cancer diagnosed via screening. Demographic details are provided in Table 1. Overall, rurality was not associated with lung cancer screening computed tomography (CT) scan (P = .36). There was not a significant difference between those diagnosed via screening and rurality (P = .76).

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Table 1.

Demographics.

Associations Between Screening History, Tumor Stage, and Treatment Modality

Patients with a history of screening were significantly more likely to be diagnosed at stages 0 to 2 than those without a screening history (66/112 [59%] vs 215/652 [33%], respectively; P < .0001). Patients without a screening history were more likely than those with a screening history to be diagnosed in stages 3 to 4 (437/652 [67%] vs 46/112 [41.1], respectively; P < .0001) as demonstrated in Figure 1.

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Figure 1.

Screening history.

Patients whose stage at diagnosis was 0 to 2 were significantly more likely to have surgery than those diagnosed at stages 3 or 4 (118/281 [42%] vs 25/483 [5.2%], respectively; P < 0.0001). Conversely, patients diagnosed at stages 3 or 4 were significantly more likely than those diagnosed at stages 0 to 2 to receive systemic therapy (318/483 [66%] vs 76/281 [57%], respectively; P < 0.0001). Systemic therapy included chemotherapy regimens and/or immunotherapy. Receiving systemic therapy was not significantly associated with a screening history (P = .17). Radiation was more likely in stages 0 to 2 than in 3 to 4 (160/281 [46%] vs 181/483 [37%], respectively; P < .0001). However, radiation was most common in stage 3 (105/144, 73%).

Patients who were screened were significantly more likely than those who were not to have surgery included as a treatment for lung cancer (46/112 [41%] vs 97/652 [15%], respectively; P < .0001). Receiving systemic therapy and radiation therapy was not significantly associated with a screening history (P = .17 and P = .54) as demonstrated in Figure 2.

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Figure 2.

Screening and treatment approach.

Survival

Survival curves following initial diagnosis differ significantly based on history of screening (P < .0001) with the rate of survival being uniformly higher with screening (n = 105, mean follow-up, 27.5 months) than without screening (n = 628, mean follow-up, 21.7 months). The Kaplan-Meier estimated survival rate at 3 years after initial diagnosis with screening history was 47.4% (95% CI, 34.8-59.0), while the rate without screening was estimated at 25.2% (95% CI, 21.2-29.4), as seen in Figure 3.

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Figure 3.

Survival and screening history.

Survival curves following initial diagnosis differ significantly based on undergoing surgical intervention (P < .0001) with the rate of survival being generally higher with surgery (n = 132, mean follow-up, 40.6 months) than without surgery (n = 600, mean follow-up, 18.1 months). The Kaplan-Meier estimated survival rate at 3 years after initial diagnosis with surgical treatment is 64.8% (95% CI: 53.1%-74.3%) while the same rate without surgery is estimated at 20.6% (95% CI: 16.8%-24.7%) as seen in Figure 4. Survival curves following initial diagnosis do not differ significantly based on receipt of systemic therapy (P = .68) as demonstrated in Figure 5. Survival curves following initial diagnosis differ significantly based on receiving radiation (P < .0001, radiation: n = 325, mean follow-up, 27.8 months; no radiation: n = 408, mean follow-up, 18.8 months). The Kaplan-Meier curves estimated survival rate at 3 years after initial diagnosis for those receiving radiation treatment was 31.8% (95% CI: 25.5%-38.1%) while the same rate without radiation was estimated at 24.9% (95% CI: 20.1%-30.1%) as demonstrated in Figure 6.

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Figure 4.

Survival and surgery.

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Figure 5.

Survival and systemic therapy.

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Figure 6.

Survival and radiation.

Discussion

Patients diagnosed with lung cancer in our health system who had undergone screening were more likely than unscreened patients to be diagnosed at an earlier stage which broadened treatment options and improved overall 3-year survival.

As more patients are screened and diagnosed, the number who are candidates for surgery will also likely increase. This is supported by an analysis from South Korea that indicated only 16% of lung cancer patients underwent surgery in 2003, compared with 25% in 2012. ⁹ We found that survival increased in those patients who had surgical intervention with a survival of 64.8% at 3 years. This survival curve was slightly less than reported in other analyses with 71% of stage 1 patients who underwent lobectomy surviving to 5 years. ⁹ However, that was comparing our 3-year data vs 5-year data sited in the study. In addition, radiation treatment was used at a significant rate in those diagnosed at an early stage and had improved survival. Both stereotactic body radiation therapy (SBRT) and surgery have been used for treatment of early-staged lung cancer. Radiation therapy is the primary curative treatment modality for patients who decline surgical intervention or those deemed not surgical candidates for early-staged cancer. ¹⁰ Surgery vs SBRT as a single entity for treatment of early-stage lung cancer remains a patient-physician decision. However, a study recently indicated that surgery provides a better overall survival compared with radiation therapy alone. ¹¹

A surprising finding was that in our demographics, rurality was not associated with whether a patient underwent a screening CT. Those who had a screening CT were just as likely to live in an area that was considered highly rural as they were to live in an urban setting. This contrasted with other studies that found screening access disparity between urban and rural settings.^7,12 In 1 study, approximately 5% of the eligible screening population lived within 40 miles of the nearest facility that offered screening CT. ¹³ A possible explanation for why this was not the case in our rural region was the number of critical access hospitals and providers in the this region that have CT scans available for the rural patients.

When patients were diagnosed at a later stage (stages 3-4), they were more likely to have chemotherapy (systemic therapy) apart of their treatment plan. This is consistent with multiple meta-analysis over the years that detailed indications for chemotherapy. Chemotherapy remains a cornerstone treatment modality for lung cancer, whether it is small cell or non-small cell. It is used as adjuvant therapy in resectable disease, as palliative treatment, and as the mainstay treatment of locally advanced cancers. ¹⁴ Our study found that 66% of those diagnosed in stages 3-4 had chemotherapy (systemic therapy) in their treatment plan. This shows that in our cohort, systemic therapy was mostly used in locally advanced disease or as palliative treatment. 27% of our cohort received systemic therapy as an adjuvant to surgical intervention. Receiving systemic therapy did not influence 3-year survival as we found that it was typically used as palliative treatment in later-staged cancers.

This study was subject to the limitations inherent to retrospective design, including missing and/or inaccurate data. Additionally, there was a potential for lead time bias that was not able to be accounted for given the retrospective nature of the study. Lead time bias causes an over-estimation of screening effectiveness. Owing to these factors, future randomized, prospective studies on the effectiveness of lung cancer screening should be conducted with corrections implemented for the anticipated lead time bias.

In conclusion, lung cancer diagnosed via screening was more likely to be diagnosed at earlier stages than those diagnosed without screening. Patients diagnosed at early stages were more likely to undergo surgery and radiation than they were to have systemic therapy. Rurality did not have a significant impact whether the patient was diagnosed via screening. Those diagnosed via screening had a higher 3-year survival rate compared with that of those who were not diagnosed via screening. These findings provide further evidence that early routine screening leads to improved treatment options and longer survival.