A nationwide analysis of disparities in guideline-concordant care in American Indians and Alaska Natives with stage I non-small cell lung cancer

Introduction

Racial disparities in the management of early-stage lung cancer are well described (1). It has been shown that Black and Hispanic populations receive lower rates of guideline-concordant care for early-stage cancer than do non-Hispanic White (NHW) patients (1), however there is limited information on American Indian/Alaskan Native (AI/AN) patients. In this growing population, which experienced an 86.5% increase from 5.2 million [2010] to 9.7 million [2020], and represents 2.9% of the United States (USA) population, the incidence of lung cancer is higher than in the NHW population, with lower survival compared to other racial and ethnic minorities (2-4). Minorities with lung cancer have a lower overall survival (OS) compared with NHW highlighting the need for studies in the AI/AN population to further assess this knowledge gap.

Racial differences in lung cancer outcomes are partially explained by patient socioeconomic status and physician behavior, as well as by systemic factors such as racism and bias (5-7). Although minority populations may share some of these factors, each group is unique and should be studied individually in order to bring about the most effective changes. AI/AN people have high prevalence estimates of tobacco use, obesity, and physical inactivity, and low prevalence estimates of fruit and vegetable consumption, cancer screening, and seatbelt use in comparison to NHW (8). In addition to these health behaviors AI/AN people have less comprehensive insurance coverage and lower utilization of healthcare than NHW (9). Studies show that AI/AN are more likely to be uninsured than NHW and that over half of low-income uninsured AI/ANs do not have access to the Indian Health Services (IHS) (9). The IHS is the health care system for federally recognized AI/AN in the USA. Even with access to IHS, AI/AN women had low rates of preventative care, which may reflect the relative lack of resources in the IHS (10).

To better understand disparities in lung cancer outcomes for AI/AN patients, we evaluated surgical treatment of stage I non-small cell lung cancer (NSCLC). This stage and pathology were chosen because surgery is potentially curative for these patients. According to the National Comprehensive Cancer Network (NCCN), the majority of patients with operable stage I NSCLC should undergo anatomic lung resection (11). Here, we use the National Cancer Database (NCDB) registry, a national hospital-based cancer data source, to describe differences in surgical treatment of stage I NSCLC between AI/AN and NHW patients and evaluate associated outcomes. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-801/rc).

Methods

Data

We performed a retrospective review of the NCDB, evaluating patients diagnosed with stage I NSCLC between 2004 and 2017. The NCDB is a joint project of the Commission on Cancer (CoC) of the American College of Surgeons and the American Cancer Society. The hospitals participating in the CoC NCDB are the source of the de-identified data used; they are not responsible for the statistical validity of the data analysis or the conclusions derived by the authors. The NCDB registries capture outcomes data for more than 1,500 CoC hospitals in the USA and Puerto Rico. The NCDB contains standardized data elements on patient demographics, tumor characteristics, including age at diagnosis, histology/hormone receptor status, stage, grade, treatments, race/ethnicity, state, and insurance status (12). The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). Given the de-identified nature of the data, the University of Minnesota IRB (STUDY00015006, 1/19/2022) has deemed evaluation of the NCDB dataset exempt from review.

Study population

We included NHW and AI/AN patients 18 years of age and older who were diagnosed with clinical stage I NSCLC between 2004–2017. Patients were excluded if they had multiple cancer diagnoses, unknown variables of interest (clinical stage, histology, race), or incomplete treatment details. We also excluded patients who underwent segmentectomy due to low numbers (n=613 in AI/AN) and the changing paradigm regarding segmentectomy as a curative cancer operation.

Definition of guideline-concordant care

According to NCCN guidelines (version 2.2023), anatomic resection with mediastinal lymph node dissection or systematic lymph node sampling is preferred for the surgical management of stage I NSCLC (13). Thus, we evaluated patients according to treatment strategy: anatomic resection or “other”. Anatomic resection was defined as lobectomy, bilobectomy, and pneumonectomy. Non-anatomic resection included patients who underwent wedge resection or non-surgical management.

Statistical analysis

Cohorts were compared using the Chi-square test for categorical variables. Variables included were demographic [race (AI/AN or NHW), age at diagnosis, sex, year of diagnosis, rural/urban residence, and Charlson Comorbidity Index (CCI)], disease-specific (tumor grade, number of nodes examined, lymph node status), and treatment (surgical management, chemotherapy, and radiation therapy). Patients were staged based on NCDB analytic stage category (stage I, II, III, IV, occult) as it was more complete than clinical stage. A sensitivity analysis was performed in which clinical stage was available. In the NCDB, the analytic stage item uses the pathologic stage and only the clinical stage group if pathologic stage is not reported. When looking at disparities in care, the clinical staging variables should be used to categorize patients given that this is the staging used preoperatively to determine the role of surgery. Patients who do not undergo surgery (those receiving discordant care) would only have clinical staging available (N=104,235).

Histologies evaluated were adenocarcinoma, squamous cell carcinoma and other. “Other” histologies included those that were categorized as non-small cell carcinoma (bronchioloalveolar carcinoma, adenosquamous carcinoma, epithelial-myoepithelial carcinoma, and metaplastic carcinoma) and therefore warranted anatomic resection. Using multivariable logistic regression, we assessed variables associated with anatomic resection. We used the Kaplan-Meier method to estimate 5-year OS. Multivariable Cox regression was used to estimate the hazard of death. Five-year OS was calculated from date of diagnosis to date of death. We used a significance level (α) of 0.05 for all analyses. Analyses were completed using SAS 9.4 (SAS Inc., Cary, NC, USA).

Results

Patient characteristics

Of 196,349 patients meeting inclusion criteria, 195,736 (99.69%) were NHW and 613 (0.31%) were AI/AN. Relative to NHW, AI/AN tended to be diagnosed in more recent years (P=0.02), were more frequently diagnosed at a younger age (P<0.001), and more commonly resided in rural locations (P<0.001) (Table 1). There were no significant differences between AI/AN and NHW with regards to sex, CCI, and pathology. A similar proportion of AI/AN and NHW underwent surgery (P=0.09) and had >15 lymph nodes examined (P=0.09).

Anatomic resection

In our multivariable analysis adjusting for all patient factors (race, sex, age at diagnosis, residence location, CCI, pathology, lymph nodes, and treatment facility), AI/AN were less likely to undergo anatomic resection than NHW [odds ratio (OR), 0.74; 95% confidence interval (CI): 0.62–0.89] (Table 2). For all patients evaluated, variables independently associated with decreased odds of undergoing anatomic resection were adenocarcinoma histology (reference squamous cell histology), CCI of 1 (reference CCI of 0), and unknown lymph node status (reference <15 nodes evaluated) (Table 2). Variables independently associated with undergoing anatomic resection were female sex, increasing comorbidities (CCI of 2 or 3), positive lymph nodes, age >65 years, and “other” tumor histology.

Survival outcomes

In our unadjusted Kaplan-Meier survival analysis for all patients, AI/AN had lower 5-year OS than NHW (58% vs. 56%, P=0.04) (Figure 1). When adjusted according to treatment strategy, the 5-year OS of patients who underwent anatomic resection was similar between NHW and AI/AN (P=0.20) (Figure 1).

Figure 1 OS of patients with stage I NSCLC by race who underwent any treatment (A) and who underwent only lobectomy or more extensive anatomic resection (excluding segmentectomy) (B), from the NCDB, 2004–2017. OS, overall survival; NHW, non-Hispanic White; AI/AN, American Indian/Alaska Native; NSCLC, non-small cell lung cancer; NCDB, National Cancer Database.

In our cox proportional hazard model evaluating patients treated with non-anatomic resection or non-surgical strategies, there was no difference in hazard of death between AI/AN and NHW [hazard ratio (HR), 1.17; 95% CI: 0.96–1.43]. Variables associated with increased hazard of death in this cohort were “other” histology types and increased CCI (Table 3).

In our cox proportional hazard model of patients who underwent anatomic resection, there was no significant difference in hazard of death between AI/AN and NHW (HR, 1.06; 95% CI: 0.92–1.22). Among AI/AN and NHW, those with adenocarcinoma had an increased hazard of death compared to those with squamous cell carcinoma (HR, 1.04; 95% CI: 1.02–1.06). In patients who underwent anatomic resection, other variables associated with increased hazard of death were age over 75 years, increased number of nodes harvested, increased comorbidities, and rural residence location (Table 3). Restricting our cohort to NCDB clinical stage did not change the magnitude or direction of our results.

Discussion

In this retrospective study using the NCDB, we evaluated management of stage I NSCLC in the AI/AN population and its association with survival. We found that AI/AN with stage I NSCLC underwent anatomic resection less frequently than NHW. AI/AN with stage I NSCLC had lower 5-year OS compared to all NHW with stage I NSCLC (56% vs. 58%; P=0.04). When comparing AI/AN and NHW who underwent anatomic resection, there was no difference in 5-year OS, suggesting that AI/AN who receive guideline-concordant anatomic resection for stage I NSCLC have outcomes comparable to NHW who receive similar treatment.

Several studies have documented a higher incidence of lung cancer and lower survival in AI/AN with lung cancer compared to NHW (4,14,15). The literature suggests that minority populations undergo anatomic resection less frequently than NHW (1,6,15). The linkage studies between cancer registries and IHS data suggest a 12% higher risk of lung cancer in AI/AN compared to NHW (3,16,17). It is not known how these patients are managed in terms of surgical and other treatment strategies. Though management could be extrapolated from studies of other minorities, dedicated research is required to evaluate outcomes in the understudied and historically neglected AI/AN population.

We describe in granular detail the characteristics of AI/AN patients with stage I NSCLC. We found that AI/AN were diagnosed at a younger age than NHW (40% vs. 28% younger than 65 years of age). Other studies evaluating epidemiology and demographics of AI/AN with lung cancer using the Surveillance, Epidemiology, and End Results (SEER) database have also reported a younger age at diagnosis in AI/AN compared to NHW (4,15,18). The Centers for Disease Control and Prevention (CDC) also reports that 23% of lung cancer cases among AI/AN were diagnosed before age 60 years compared with 16% among NHW (17). Prevalence of tobacco use among AI/AN relative to NHW could be a contributing factor (19). Cornelius et al. found that AI/AN have the highest prevalence of current tobacco use in comparison to other races (20).

We did not find a difference in the incidence of stage I NSCLC between male and female patients in NHW and AI/AN, nor a difference in survival when stratified for sex. This is similar to most other published data evaluating the AI/AN population (15,17). There are, however, several studies that demonstrated women have a survival advantage compared to men with lung cancer (21).

In other large database studies, Smith et al. and Javid et al. (4,14) described lower rates of surgical resection in AI/AN. These studies included all potentially operable lung cancers (stages I–IIIA) and hence included a wider range of patients. Our study found the same disparity even when focused only on stage I NSCLC. This finding is in line with findings in other minority populations. Hispanic patients with early stage, potentially resectable lung cancer are less likely to receive the standard-of-care treatment (22). DeShazer et al. found that Black Americans underwent surgery significantly less frequently for stage I and II lung cancer compared to NHW (1). Similar findings have been described by Balekian et al., Chau et al., and Wolf et al. (23-25).

Guideline-concordant care, as recommended by the NCCN, includes sampling or dissection of at least three ipsilateral mediastinal lymph node stations (N2) and mapping of N1 and N2 nodes. This detail on lymph node dissection was unavailable in the NCDB, so we did not evaluate this variable in our study. There is no published data evaluating lymph node resection patterns in AI/AN. Studies in other minority populations have indeed shown that these groups are significantly less likely to have more than 15 nodes examined (25,26).

We found that AI/AN with stage I NSCLC had lower 5-year OS when compared to NHW. Although statistically significant, the small absolute survival difference is of uncertain clinical significance. When comparing AI/AN and NHW who underwent anatomic resection, the difference in 5-year OS was no longer apparent. Variables that could potentially affect survival such as CCI, tumor characteristics or number of lymph nodes examined were not significantly different between AI/AN and NHW in our study. This suggests that delivery of adequate care to this population could help reduce survival disparities, even if they are minor. Wolf et al. described similar findings in Black and NHW patients with early-stage lung cancer (25). They found that univariate 5-year OS was lower for Black patients than NHW patients, but when stratified by treatment type, those survival differences were not significant.

Minimizing disparities in survival requires that AI/AN patients receive high-quality care. This largely depends on mitigation of disparities throughout the healthcare system. There are documented disparities in health coverage and care showing that AI/AN continue to be at a disadvantage in the USA health system, with uninsurance rates at much higher rates than NHW (9). Although the IHS provides a valuable source of basic health care for some AI/AN who lack insurance coverage, there are gaps in preventive care that could contribute to findings in this study (27).

Fewer AI/AN patients receive cancer-directed therapies after diagnosis than NHW, which is likely related to socioeconomic factors such as lower income and rural residency. An analysis of the largest all-payer data source for hospital admissions in the USA (excluding Alaska) found that among hospitalized cancer patients, AI patients were more likely to live in low-income zip codes, more likely to have Medicaid, and more likely to have their cancer surgeries performed at a rural hospital (28). Although not evaluated in this study, it has previously been described that a small proportion of hospitals provide a disproportionate amount of surgical care for racial and ethnic minorities with lung cancer, albeit with higher mortality, complications, and readmissions, and a larger portion of these surgeries being emergent rather than elective (29,30).

Culturally tailored programs in some communities have been shown to mitigate the observed cancer-related health disparities among AI/AN (31). Cultural issues specific to certain tribes, regional gradients of inequity, geography, and a multitude of other factors contribute to the fact that any program will need to be regionally tailored to serve its target population by addressing barriers and reducing health disparities (32).

The limitations of our study include the limitations of large database research in general: reliance on coding, data which can be incomplete, and sample size. Despite the broad range of data captured in the NCDB, the sample size of the AI/AN cohort was small and may limit the power of our analysis. Additionally, AI/AN may be under-reported in the NCDB due to racial misclassification (33).

We are unable to comment on patient-level factors that are not included in the NCDB, such as smoking history, lung function, family history of lung cancer, and obesity, which could affect patient suitability for anatomic versus non-anatomic resection or non-surgical treatment. In some cases, segmentectomy and wedge resections are necessary in patients with poor pulmonary function, or in those with small peripheral lesions of certain histology. Additionally, the NCDB does not include granular data on lymph node sampling or dissection, or cancer-specific survival. We chose to use the NCDB because it collects data from CoC-accredited institutions which ought to adhere to best practices and surgical standards, and because it includes the CCI, which is important variable in evaluation of surgical patients (14). Despite these limitations, our study provides a detailed evaluation of surgical management of NSCLC in a population that is traditionally difficult to study, and underscores the importance of anatomic resection for optimal survival outcomes.

Conclusions

AI/AN with stage I NSCLC undergo anatomic resection less frequently than NHW, with a slight decrement in survival. This difference was not seen among AI/AN patients undergoing guideline-concordant anatomic resection. Our findings provide a discrete area for future intervention, in that guideline-concordant surgical treatment for AI/AN with stage I NSCLC may result in improvements in mortality in this population. Potential areas of future research include analyzing the availability and utilization of lung cancer screening in AI/AN, as well as evaluation of rural and urban AI/AN access to thoracic surgeons.

Acknowledgments

Initial data from this research was presented at the 2022 American Association for Thoracic Surgery (AATS) meeting in New York, USA.

Funding: This work was supported by the Diversity, Equity, and Inclusion grant from University of Minnesota Department of Surgery.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-801/rc

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-801/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-801/coif). A.B. serves as an unpaid editorial board member of Journal of Thoracic Disease from October 2021 to September 2023. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). Given the de-identified nature of the data, the University of Minnesota IRB (STUDY00015006, 1/19/2022) has deemed evaluation of the NCDB dataset exempt from review.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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