Cancer in rural America: Improving access to clinical trials and quality of oncologic care

Abstract

Individuals from rural areas in the United States suffer higher rates of morbidity and mortality from cancer than their urban counterparts. This review is based on the idea that equity—the elimination of unnecessary and preventable differences between groups of individuals—should underlie access to cancer care resources for patients from rural areas. Access to cancer clinical trials serves as the framework for identifying and understanding barriers in access to quality oncologic care. The authors discuss the interplay between rural living, socioeconomic status, culture, and health; and they highlight how economic considerations in rural areas often limit access to clinical trials and oncologic care because economies of scale do not apply in these regions given the requirement for high‐quality oncology care even with lower patient volumes. The authors propose solutions to enhance access to clinical trials and improve the quality of oncologic care in rural areas, viewing these aims as ethical and moral imperatives.

INTRODUCTION

Equitable access to health care resources in the United States has received tremendous attention in the lay and scientific literature in the past decade. Research regarding cancer health care disparities has routinely focused on individual‐level social determinants defined by levels of race, ethnicity, sex, age, educational achievement, and socioeconomic status. However other determinants can define large groups of individuals with limited access to health care resources. The World Health Organization defines equity as the absence of avoidable, unfair, or remediable differences between groups defined either socially, economically, demographically, or geographically. ¹ The latter domain, geography, has particular relevance in the United States, with its long distances between urban areas, especially across the intermountain and Midwest regions. In the United States, rural versus urban populations are commonly characterized by measures of population density, urbanization, and daily commuting. ² A focus on the special needs of individuals living in rural areas was highlighted in the Cancer Moonshot Blue Ribbon report in 2016, which noted that some populations in the United States, such as racial/ethnic minorities, those from urban and rural areas, or poor and medically underserved individuals, continue to suffer disproportionately from some cancers and have higher rates of morbidity and mortality. ³ The notion that equity should underlie access to cancer care resources for all patients with cancer, including those from the vast rural areas of the United States, is the ethical predicate that motivates this review.

This review aims to highlight issues around access to both cancer clinical trials and quality oncologic care in rural areas. In this context, the study of access to clinical trials can serve as the canary in the coal mine, reflecting broader issues regarding access to quality oncologic care in rural communities. Our premise is that the best treatments are received in clinical trials, that clinical trials provide access to tomorrow's treatment today, and that the ability to participate in clinical trials also reflects the ability to adopt new clinical trial findings. ⁴ Furthermore, the increased demands required by the clinical trials infrastructure is a stress test that reflects the ability to provide high‐quality care in rural communities. Key themes throughout will pertain to the intersection of rurality and socioeconomic status; the interplay between culture and poverty; and, relatedly, limitations on the economic infrastructure available in rural areas to support both the conduct of trials and access to quality oncologic care. The review also implicitly acknowledges that economies of scale do not apply in rural areas, where the need for quality cancer care persists despite lower patient volumes. And yet, providing this care is an ethical, moral, economic, and sociopolitical imperative.

THE SCOPE OF RURAL CANCER DISPARITIES

Approximately 19% of the US population, which includes a similar percentage of individuals with cancer, resides in rural areas. ⁵ , ⁶ Individuals with cancer living in rural areas have poorer outcomes compared with their urban counterparts. From 2011 to 2015, the age‐adjusted rate of cancer deaths in rural areas was 180.4 per 100,000, whereas, in large metropolitan areas, it was 157.8 per 100,000. ⁵ These disparities are attributed in part to limited access to medical, technological, and financial resources, including lower rates of health insurance and cancer screenings and increased behavioral risk factors for poor cancer outcomes. ⁷ , ⁸ , ⁹ , ¹⁰ , ¹¹ Consequently, detection and treatment can be delayed, and patients with cancer from rural areas exhibit, on average, later stage of disease at diagnosis and receive treatment that begins later in the course of disease. ¹² , ¹³ , ¹⁴ In fact, differences in cancer outcomes for these patients in the United States are growing rather than shrinking. ⁵ , ¹⁵ , ¹⁶ , ¹⁷

In rural areas, observed disparities are exacerbated among those with higher levels of deprivation, from more remote (i.e., frontier) areas, in males, and in racial and ethnic minority populations. ¹⁸ , ¹⁹ Singh and colleagues used a deprivation index with 11 census‐based social indicators to demonstrate that, between 2003 and 2007, age‐adjusted cancer mortality consistently increased as the level of socioeconomic deprivation increased from 168.0 per 100,000 for those in the least deprived areas to 200.2 per 100,000 for those in the most deprived areas. ¹⁸ Much of the gradient in rural/urban disparities in mortality is attributable to excessive deaths among males from rural areas, with a cancer mortality rate of 240.3 per 100,000 for males in rural counties compared with 217.6 per 100,000 from large metropolitan areas; in contrast, among females, the difference is much smaller (157.6 vs. 154.4 per 100,000). ¹⁸ Probst and colleagues demonstrated that, between 2013 and 2017, the age‐adjusted cancer mortality rate per 100,000 residents was higher for individuals from rural versus urban areas for Asian/Pacific Islander (107.7 vs. 101.0), Black (203.1 vs. 188.3), and White (181.0 vs. 164.6) populations. ¹⁹ There was also strong evidence that these domains intersected. For instance, the all‐cancer mortality rate per 100,000 for Black males from the most deprived areas was 320.2 per 100,000. ¹⁸

The largest rural/urban mortality discrepancy was within the American Indian/Alaskan Native population, with an age‐adjusted cancer mortality rate per 100,000 residents of 164.7 for those from rural areas compared with 123.4 for those from urban areas. This dramatic difference suggests the potential challenges of providing cancer services for special populations in rural areas. For instance, the colorectal cancer rate among the Alaska Native population is approximately twice that of Whites in the United States. ²⁰ A randomized trial was conducted to assess whether a multitarget stool DNA test might improve screening rates. The trial faced practical difficulties, with a lack of laboratory space and mail service delays, which were exacerbated by the coronavirus disease 2019 (COVID‐19) pandemic and necessitated study adaptations. ²¹ However, the study ultimately reached its enrollment goal, indicating that cancer screening interventions may be successfully administered in this population. ²² The high cancer mortality rate in native US populations and the challenges of administering care motivated our inclusion of a case study highlighting challenges to providing cancer clinical trials and quality oncologic care in this population (see Table 1). ²³ , ²⁴ , ²⁵

TABLE 1.

Case study: Access to clinical trials in the Navajo Nation.

The Navajo Nation is an Indian reservation of Navajo people in the United States, occupying portions of northeastern Arizona, northwestern New Mexico, and southeastern Utah. 23 The reservation is populated by Native Americans. The median household income in 2023 was $33,592, and poverty levels are high (38.3%) 24 ; one third of the Navajo population does not have electricity and running water. Access to health care is provided through Indian Health Service facilities, Medicaid, Medicare, and some commercial insurance. New Mexico Oncology Hematology Consultants (NMOHC) provides a case study into the difficulties of providing clinical trials in a rural area. NMOHC is an independent, multidisciplinary, cancer‐focused practice with a cancer center in Albuquerque, New Mexico, and, since 2007, a cancer center in Gallup, New Mexico (the medical heart of the Navajo Nation) that provides both medical oncology and radiation oncology services. NMOHC enrolls approximately 20–30 patients per month into clinical trials in the Albuquerque office. No patients have been enrolled by the practice in the Gallup office, although the same physicians staff both clinics. In the Albuquerque clinic, NMOHC has well‐trained research staff. The Albuquerque clinic has adequate pharmacy support, infusion nurses, and support staff. In the Gallup clinic, the practice struggles to find, train, and retain support staff and the technical staff needed for cancer care. Gallup, which is 140 miles west of Albuquerque, lacks the highly‐trained research staff needed to run a clinical trial program. Without a sufficient number of patients to enroll into trials, the conduct of a clinical trial program would be a financial liability for the center. NMOHC has found that providing care in Gallup is far more resource‐intensive than providing care to patients in Albuquerque. In part, this is because patients often lack adequate personal and financial resources. In such cases, the practice provides for the needs of patients, including arranging transportation to the clinic, ensuring adequate food and shelter, and assisting patients with family responsibilities. These additional tasks take far more time for practice personnel to undertake than the same functions do in the more affluent urban area of Albuquerque. Traveling across the reservation to get to NMOHC's clinic in Gallup is a major financial burden for patients. Multigeneration families often live in compounds on their ranch; family ties are very strong and are an important part of the culture. Sometimes, only one vehicle is available for an entire family, which is used to get the children to school, to pick up supplies, and to transport those who work in town to their jobs. When a patient is diagnosed with cancer, the entire family often wishes to be involved. When this occurs, all of the adults miss work, and the children miss school. If the livestock are not properly cared for, ranchers may not have adequate food for the following winter. The loss of the family members' paychecks during times of acute illness can be financially devastating. Participation in a clinical trial requires a commitment from the patient that is far greater than that required to get standard cancer care. For families on a limited income, if they can save the cost of a tank of gas by getting a ride into the clinic, it makes economic sense to do so, even if it does not fit the clinic schedule. For a patient on a clinical trial, such a nonscheduled visit may represent a protocol violation. If the trial is not offered locally, the expense of travel, housing, and feeding the family to attend an academic medical center in an urban area is often beyond what is financially feasible. Patients who have spent their entire lives supporting their families will not choose to accept a trial that is financially prohibitive. Other expenses could include the need to arrange for childcare, meals out of town, and lost wages, including for family members accompanying patients. Farmers and ranchers may need to pay someone to feed their livestock. Distrust of clinical research is also high. The Indian Health Service is given by Congress, on average, $4078 per year for every patient they care for, compared with $8109 for those in Medicaid, $10,692 for those in the Veterans Health Administration, and $13,185 for those in Medicare. 25 Underfunding results in long delays in payments to external clinics and facilities. Although the Indian Health Service is required to pay for the nonexperimental expenses of clinical trials, in practice, trial participation is not prioritized given inadequate total reimbursement for trial participation compared with other clinic priorities. In summary, even if other barriers could be overcome, a community without adequate access to care that is affordable and comprehensive will never invest in clinical trials. The first task to expand clinical trials into underserved areas, therefore, must be to adequately fund the health care infrastructure.

CANCER CLINICAL TRIALS: A FRAMEWORK FOR UNDERSTANDING BARRIERS AND DISPARITIES IN PARTICIPATION

Patient participation in clinical trials is crucial for advancing cancer research and improving treatment outcomes. With increased participation, trials can be conducted more efficiently, and new treatments can be discovered (and ineffective treatments rejected) more rapidly, benefiting all patients. Furthermore, clinical trials offer patients the chance to access the latest available treatments, so access to trials should be fair and easily attainable for all patients.

Only 6%–8% of adults with cancer participate in clinical trials, although most Americans view clinical trial participation favorably. ²⁶ , ²⁷ , ²⁸ , ²⁹ Thus there is a large gap between the willingness of patients to participate in trials and actual trial participation rates. This difference highlights the numerous barriers to cancer trial participation that patients face.

A 2019 review provided a framework to characterize the dominant barriers to participating in treatment trials. ²⁷ When engaged in treatment decision making about trial participation, a determination must first be made about whether a trial is locally available (Figure 1). If a clinical trial is available, patients are evaluated to determine whether they meet the eligibility criteria. If a physician determines it is appropriate, they may offer the trial to the patient. At this point—only at the very end of the decision‐making process—the patient has the agency to decide whether to participate. ³⁰ Moreover, along this pathway, there may be differences according to demographic, socioeconomic, and geographic factors that characterize a patient's background and experience.

FIGURE 1.

Barriers and complications in receipt of cancer care in patients living in rural areas: a conceptual model.

An understanding of the dominant barriers to trial participation for patients with cancer from rural areas is important because participation in cancer clinical trials provides access to the newest available treatments. Just as today's standard treatment was yesterday's clinical trial, clinical trials offer patients potential access to tomorrow's treatment, today. Much of medical discovery historically occurred at the bedside in small institutions within local communities. ³¹ However, as urban and rural areas drifted apart, research increasingly shifted away from bedside observation and focused more on laboratory studies. ³² Although this shift was important for advancing our understanding of the molecular biology of disease, it is essential to broaden our focus to ensure that laboratory discoveries are quickly and effectively implemented in various settings. A significant challenge in this effort is addressing the needs of rural communities. Bridging this gap will maximize the benefits of medical discoveries for all populations.

There is universal agreement that enrollment in a clinical trial not only advances the science but provides patients with the opportunity for state‐of‐the‐art care; patients may even have the opportunity to avoid the cost of the drug if the trial sponsor provides it. ³³ Participation in cancer clinical trials has been shown to ameliorate cancer outcome disparities among patients from rural areas. In a 2018 study of 36,995 enrolled in clinical trials over 37 years, patients from rural areas with a wide variety of cancer types had similar outcomes compared with their urban counterparts. ³⁴ Equally important, an understanding of the barriers and hurdles that these patients face in accessing cancer clinical trials can also represent a biomarker for an adequately funded, affordable, comprehensive health care system trusted by the people it serves.

Structural factors

The large majority of patients with cancer receive their treatment in community practices, with estimates exceeding 80%. ³⁵ , ³⁶ , ³⁷ Nevertheless, trial participation in community practices is uncommon. In a study of 1200 accredited oncology care institutions nationwide, only 4% of patients treated in community cancer clinics participated in a clinical trial, compared with greater than 20% treated at large, generally urban academic research institutions. ²⁶

In geospatial studies, clinical trial sites tend to be highly clustered around urban areas. ³⁸ The scarcity of institutions that conduct trials outside major urban areas stems from the significant resources and institutional commitment needed to establish a cancer clinical trial program. ³⁹ In the United States, physicians working in independent clinical practices are paid under the Physician Fee Schedule for Medicare patients, which provides approximately one half of the payment for care given under the Hospital Outpatient Prospective Payment System to hospitals. It has been estimated that payment (in 2024 US dollars) to independent practices is 29% less than in 2001, whereas practice expenses have increased 46%. ⁴⁰ , ⁴¹ , ⁴² Therefore, rural practices often do not have the funds to pay clinical trial staff or to take the additional time and work to provide clinical trials to patients; and rural hospitals, already economically stressed in providing basic clinical services, are often unable to attain the infrastructure necessary for providing clinical trials. Nearly 90% of patients enrolled in cancer treatment trials in the United States participate in trials sponsored by pharmaceutical companies rather than in federally sponsored trials. ⁴³ Thus trials in large urban hospitals are predominantly sponsored by industry. Academic research hospitals are staffed by clinician‐scientists and researchers with the trial expertise that allows pharmaceutical companies to support (through capitation payments) the testing of new drugs in a setting with the scientific and logistical expertise necessary to meet the burdensome requirements for a new drug application to the US Food and Drug Administration (FDA). Community‐based cancer care centers generally do not have the resources to build such clinical trial infrastructure. Because cooperative group trials often have multiple arms, strict inclusion/exclusion criteria, prolonged data collection, and inadequate payment, they may be less attractive to community‐based practices or hospitals that do have research infrastructure.

The absence of a locally available trial represents a structural barrier to trial participation, with outsized implications for patients living in rural areas. One study indicated that 86% of nonmetropolitan counties had no trials available, compared with 44% of metropolitan counties. ⁴⁴ With few trial sites outside urban areas, patients from rural areas must travel farther to participate in a trial. This pattern is illustrated in Figure 2. By using data from 29,546 patients enrolled in cancer clinical treatment trials conducted by the SWOG Cancer Research Network over 30 years, the mean travel distance to the site of trial conduct was 2.5 times greater for patients from rural areas compared with patients from urban areas. Nearly three in four patients from rural areas (73.8%) traveled >50 miles to participate in a trial, compared with only one in six patients (16.2%) from urban areas. These statistics may actually understate the burden of travel for patients from rural areas because a proportion of patients from urban areas traveled long distances to participate in a trial, including 8.1% traveling >100 miles. This pattern, in which urban patients sometimes choose to travel a long distance to participate in a trial, generally at a large academic center such as National Cancer Institute (NCI)‐designated Cancer Centers, is probably much less likely for rural dwellers. ⁴⁵ Therefore, if we adjusted for the choice to travel far, the disparity in clinical trial access between urban and rural patients with cancer would likely be even greater. In general, it is difficult for patients to undertake the disruption of their family schedules and the depletion of family finances for a trial that requires them to be away from their support community.

FIGURE 2.

Rural versus urban differences in travel distance to participate in a clinical trial. Data were from N = 29,546 patients enrolled in cancer clinical treatment trials conducted by the SWOG Cancer Research Network over 30 years. (A) A map of the contiguous 48 states with straight‐line travel distances for patients living in urban areas. Dark blue lines indicate that the travel distance was >50 miles, and light blue lines indicate that the travel distance was <50 miles. (B) A histogram of travel distances for patients living in urban areas. (C) A map of the contiguous 48 states with straight‐line travel distances for patients living in rural areas. Dark red lines indicate that the travel distance was >50 miles, and light red lines indicate that the travel distance was <50 miles. (D) A histogram of travel distances for patients living in rural areas.

Compared with metropolitan systems, the rural health care system is more dispersed, with fewer clinicians, including generalists and specialists, such as oncologists, radiologists, pathologists, surgeons, and radiation oncologists. In addition, there are fewer hospitals and treatment facilities, very few dedicated rural cancer centers, and fewer resources, such as laboratories and radiation therapy services. The infrastructure in these areas is also less, with challenges like limited internet access and electronic health records. ⁴⁶ , ⁴⁷ , ⁴⁸ Consequently, for patients seeking standard oncology care outside of a trial, most must travel outside their county. Two thirds (67%) of all nonmetropolitan US counties had no hematologists or oncologists; in contrast, the proportion for metropolitan counties was one half that (34%). ⁴⁹ Data from the Pennsylvania Cancer Registry indicated that the average travel time for a clinic appointment was more than threefold greater for those living in the most rural areas than for urban residents. ⁵⁰ Another study demonstrated that the average travel distance to a radiation facility for patients with breast cancer was threefold greater for rural patients compared with urban patients. ⁵¹

The need to travel long distances to receive cancer treatment (on or off trial) has worsened since the financial crisis of 2009. Financial pressures have resulted in many centers closing, accentuating the crisis in accessibility of care. ⁵² According to tracking data from the University of North Carolina, there have been 193 rural hospital closures over the past 2 decades (Figure 3). ⁵³ More than three quarters of these represent complete closures; in the remaining instances, facilities were converted to provide more limited services, such as primary care.

FIGURE 3.

Rural hospital closures since 2005. According to tracking data from the University of North Carolina, there have been 193 rural hospital closures over the past 2 decades. More than three quarters of these represent complete closures; in the remaining instances, facilities were converted to provide more limited services, such as primary care. The bar graph shows number of closures and conversions in 2‐year periods by type of closure. The inset shows the cumulative number of complete and converted closures over time.

Clinical factors

Cancer clinical trials are designed to enroll individuals who are at lower risk for adverse consequences of experimental treatment. Thus patients with comorbid conditions that might threaten their ability to tolerate experimental therapy are routinely excluded. Restricting trials to patients with a consistent health profile also reduces trial heterogeneity and thus allows trials to better isolate the causal effect of a new treatment. ⁵⁴ However, eligibility criteria have increased over time, in part because of the lack of conscientious efforts to tailor trial eligibility criteria to each trial. ⁵⁵ , ⁵⁶ One study indicated that the average number of eligibility criteria per trial was 16, of which 60% were related to other disease conditions or the patient's overall health status. ⁵⁷ In part for this reason, even when a trial is available for a patient's cancer, one half of the patients are clinically ineligible to participate. ²⁷ Thus the strategy of reducing trial heterogeneity comes with costs. Narrow eligibility criteria limit access to the newest treatments available in clinical trials. Moreover, confidence about the external validity of trial results is weakened if the trial eligibility criteria define only a narrow, generally healthier population of individuals with cancer.

The restrictiveness of clinical trial eligibility criteria has outsized implications for patients from rural areas. It has been demonstrated that rural residents have greater disease burden than those living in urban areas. In a study of 214,000 individuals surveilled in the US Centers for Disease Control and Prevention's 2008 Behavioral Risk Factor Surveillance System, the prevalence of coronary heart disease was 5.5% in rural individuals and 4.0% in their urban counterparts: a 37.5% relative difference (Table 2). ⁵⁸ Data from the 2017 National Health Interview Survey indicated a relative 42.5% higher prevalence estimate of diabetes in rural versus urban populations (11.4% vs. 8.0%). ⁵⁹ Other estimates of differences in prevalence have been less stark. ⁵⁸ , ⁶⁰ Individuals from rural areas are also more likely be obese (34.2% vs. 28.7%), hypertensive (40.0% vs. 29.4%), and to have chronic obstructive pulmonary disease (8.2% vs. 4.7%) as well as several other common disease conditions. ⁵⁸ , ⁵⁹ , ⁶⁰ , ⁶¹ , ⁶² , ⁶³ , ⁶⁴ , ⁶⁵ , ⁶⁶ , ⁶⁷ , ⁶⁸

TABLE 2.

Prevalence of common disease conditions in rural versus urban areas.

	Rural	Urban	Relative Increase (%)	Notes	Source
Arthritis	31.8	20.5	55.1	Unadjusted	https://pubmed.ncbi.nlm.nih.gov/28542117/
	26.9	20.0	34.5	Age standardized	https://pubmed.ncbi.nlm.nih.gov/28542117/
Asthma	8.5	7.8	9.0	Large metropolitan vs. rural a	https://pubmed.ncbi.nlm.nih.gov/34529643/
COPD	8.2	4.7	74.5	Age adjusted	https://pubmed.ncbi.nlm.nih.gov/29470455/
Depression	6.1	5.2	17.3		https://pubmed.ncbi.nlm.nih.gov/17009190/
	7.8	7.1	9.9		https://uknowledge.uky.edu/ruhrc_reports/14
Diabetes	9.7	9.0	7.8	Unadjusted	https://pubmed.ncbi.nlm.nih.gov/22922043/
	9.9	9.0	10.0	Age adjusted	https://pubmed.ncbi.nlm.nih.gov/22922043/
	9.0	7.7	16.9		https://pubmed.ncbi.nlm.nih.gov/20386968/
	11.4	8.0	42.5		https://pubmed.ncbi.nlm.nih.gov/32078375/
CHD	5.5	4.0	37.5	Unadjusted	https://pubmed.ncbi.nlm.nih.gov/22922043/
	4.9	4.0	22.5	Age adjusted	https://pubmed.ncbi.nlm.nih.gov/22922043/
High cholesterol	42.4	38.8	9.3		https://pubmed.ncbi.nlm.nih.gov/27584875/
Hypertension	40.0	29.4	36.1		https://pubmed.ncbi.nlm.nih.gov/32379728/
Obesity	34.2	28.7	19.2		https://pubmed.ncbi.nlm.nih.gov/29902166/

Abbreviations: CHD, coronary heart disease; COPD, chronic obstructive pulmonary disease.

^a Derived as the mean of the region‐specific prevalence estimates comparing large metropolitan statistical areas versus nonmetropolitan statistical areas (i.e., rural).

A greater prevalence of comorbid conditions among rural patients with cancer makes them less likely to meet trial eligibility criteria, locking them out of the benefits of clinical trial participation, including receipt of the newest available treatments and the opportunity to receive protocol‐guided cancer treatment. Moreover, a greater disease burden increases the physical burden of travel, which can lead to reduced access to, and opportunity to participate in, a trial or even to receive standard care outside a trial. Rural patients with cancer are roughly one half as likely to receive breast‐conserving therapy for early stage breast cancer compared with the national average; these rates drop even further with increasing travel distance. ⁶⁹ A large study of nearly 35,000 patients indicated that those with stage III colon cancer who had to travel very long distances (>250 miles) to visit an oncologist were only one third as likely to receive adjuvant chemotherapy. ⁷⁰

Physician factors

Most physicians (>80%) agree that clinical trials provide high‐quality care and benefit patients. ⁷¹ Yet, among eligible patients at sites with available trials, physicians decide against enrollment more than one half the time, ⁷² , ⁷³ with studies suggesting that preferences for specific treatments are a predominant factor at play. ⁷⁴ , ⁷⁵ , ⁷⁶ A study that prospectively assessed both physicians' and patients' attitudes about trial decision making demonstrated that the desire to use a specific treatment was the reason for not discussing a trial with eligible patients more than one half the time. ⁷⁷ Physicians are also frequently concerned that clinical trial participation can interfere with the physician–patient relationship, especially given the experimental nature of trials and the use of randomization to determine treatment choice. ⁷⁴ , ⁷⁸ , ⁷⁹ This can generate uncertainty among patients when physicians are otherwise expected to provide affirmative guidance about treatment choices.

Some reasons that preclude physician interest in offering trials to their patients are likely to be especially acute in rural oncology care sites. Rural oncology resources are sparse. Although 20% of the population lives in rural areas, the proportion of oncologists working in rural areas is low, estimated between 3% and 7%. ⁴⁸ , ⁴⁹ In this underserved setting, oncology professionals are more likely to lack the support or incentives to participate in clinical research, including the uncompensated time spent explaining clinical trials to patients and attending to the details of clinical trial enrollment. ⁷¹ , ⁷⁴ , ⁷⁶ , ⁸⁰ , ⁸¹

Physicians in rural communities often have difficulty finding the range of services needed to provide care for their patients, such as rapid access to surgical care or to nearby radiation therapy services. Moreover, physicians and advanced practice providers are disproportionately located in areas where their spouses can find jobs and their children will have adequate school systems. Absent these resources, physicians may believe that choosing a rural area to work will mean they will not have adequate support to provide the high quality of care they were trained to provide or the quality of life they had anticipated for their family. The disincentives built into the lived experience of physicians in rural areas have resulted in an aging rural physician workforce short on early career providers. One study indicated that, in 2017, approximately 53% of rural physicians were aged 50 years or older, compared with only 39% in urban areas, representing a graying of the rural physician workforce that is expected to continue in the years ahead. ⁸² Moreover, insurance payments for provided care are often restrictive for rural beneficiaries. One recent study indicated that rural beneficiaries face disproportionately high restrictions in specialty provider networks in Medicare Advantage plans. ⁸³

Patient factors

The final decision about participating in a trial belongs to the patient and reflects their personal preferences, although it also may be influenced by family and friends. ⁸⁴ Although some patients are motivated by altruism, the majority prioritize finding the best treatment for their disease. ⁸⁵ , ⁸⁶ , ⁸⁷ In short, patients are more likely to participate in a trial if they believe it offers the best treatment option. ⁷⁶

Patients often decline to participate in clinical trials out of fear or unease about the process. ⁸⁸ A fear of experimentation can manifest as a dislike of randomization, which is the most frequently cited reason for declining participation in trials. ⁷³ , ⁸⁷ , ⁸⁹ , ⁹⁰ , ⁹¹ , ⁹² Fear of experimentation is likely rooted in a lingering mistrust of medical science because of past abuses, such as the infamous Tuskegee Syphilis Study and the history of human experimentation with radiation after World War II, abuses that have had a lasting legacy, especially among socioeconomically vulnerable patient populations. ⁹³ , ⁹⁴

Mistrust of medical science is a more prominent phenomenon among rural individuals that adversely affects participation in clinical trials or even acceptance of standard care. ⁹⁵ This distrust was widely evident during the COVID‐19 pandemic, when notably fewer individuals in rural communities received COVID‐19 vaccines. ⁹⁶ Even before the COVID‐19 experience, individuals from rural areas were more predisposed to distrust science and scientists. ⁹⁷ , ⁹⁸ Cultural distrust may arise from a perceived disconnect with government institutions, which may seem indifferent to the realities of rural life. ⁹⁹ It also may be accentuated among vulnerable populations within rural areas, such as racial and ethnic minorities. ¹⁰⁰

Cost concerns are a frequently indicated reason for nonparticipation in trials. ⁸⁷ , ⁸⁸ Trial participation is associated with both direct costs, such as copays and coinsurance costs, and indirect costs, including time off work, childcare, and travel/transportation. ¹⁰¹ The multidimensional nature of direct and indirect costs explains the persistent reluctance to participate in trials even though most states require both commercial and governmental insurers to cover the routine care costs associated with these trials. ⁸⁷ , ¹⁰² , ¹⁰³

The necessity to travel to receive trial or nontrial care can impose a significant financial burden on patients with cancer and their caregivers, in both travel and time off work. This situation is particularly challenging for rural dwellers, whose household incomes are consistently 25% lower than their urban counterparts. ¹⁰⁴ In 2021, US per capita income was $49,895 in rural areas compared with $66,440 in urban areas. ¹⁰⁵ Similarly, the poverty rate was 15.4% in rural areas compared with 12.3% in urban areas.

The higher prevalence of poverty among rural communities highlights the important role of social insurance programs in filling gaps in health care access. The Patient Protection and Affordable Care Act (ACA) changed how many patients acquire insurance, introduced new protections, and increased the number of individuals with insurance coverage. ¹⁰⁶ , ¹⁰⁷ , ¹⁰⁸ A key aspect of the ACA was expanding Medicaid eligibility to individuals with incomes up to 138% of the federal poverty level. ¹⁰⁹ Individual states have had the option to adopt the measure and, in return, receive increased federal support for Medicaid. Medicaid expansion led to increased utilization of Medicaid insurance across the country, particularly in states that implemented the Medicaid expansion program. ¹⁰⁸ This trend was also observed among patients with cancer. ¹¹⁰

As of 2024, 10 states had not adopted Medicaid expansion, and many that had often took several years to do so. This trend was especially evident among states with large rural populations. As illustrated in Figure 4, 25 states and the District of Columbia implemented the ACA Medicaid expansion when it first became available, on January 1, 2014. ¹¹¹ The rural proportion among these states was 14.3%, much less than the national average of 19.9%. ¹⁰⁵ , ¹¹¹ , ¹¹² As years progressed, additional states adopted the expansion; these states were increasingly rural in their makeup, such that the rurality level of ACA Medicaid expansion states has continued to increase over time. Among the remaining 10 states that have not yet adopted the Medicaid expansion, the rural proportion is 23.1%, demonstrating a consistent pattern whereby more rural states have been slower to adopt this expansion of the social safety net.

FIGURE 4.

Percentage rural among states that adopted the ACA Medicaid expansion over time. Based on data from the Kaiser Family Foundation, 25 states and the District of Columbia implemented the ACA Medicaid expansion when it first became available, on January 1, 2014. ¹¹¹ The rural proportion among these states was 14.3%, much less than the national average of 19.9%. ¹⁰⁵ , ¹¹¹ , ¹¹² As years progressed, additional states adopted the expansion; these states were increasingly rural in their makeup, such that the proportion of states having adopted the ACA Medicaid expansion has continued to increase over time. The individual states adopting the Medicaid expansion at each time period are shown according to their state acronym above each bar. Among the remaining 10 states that have not yet adopted the Medicaid expansion, the rural proportion is 23.1%, demonstrating a consistent pattern whereby more rural states have been slower to adopt this expansion of the social safety net. ACA indicates the Patient Protection and Affordable Care Act.

POTENTIAL SOLUTIONS

Taken together, issues of remote geography, limited availability of cancer care centers, the need to travel long distances, lower income, and greater poverty create special challenges for patients with cancer from rural areas as they pertain to both trial participation and receipt of quality, nontrial oncologic care. The intersection of these domains contributes to a systemic structural difference between rural and urban communities, which has been termed structural urbanism by Probst and colleagues. ¹¹³ These structural biases result from a market‐based approach to health care funding; a focus on optimizing population‐level health outcomes, with an accompanying emphasis on large population centers; and an inherent inefficiency of delivering health care services in remote, low‐population settings. ¹¹³

To improve cancer health care access and outcomes for patients with cancer from rural areas, the health care system must be oriented to find ways to bring care to the patients or, alternatively, to improve ways to bring the patients to care, while also providing patients the resources, including the physician resources, to access care. Moreover, despite the challenges, establishing a research culture within rural communities can have multiple benefits that extend to aspects of rural living beyond the treatment of a single disease, including increased economic activity, improved health behaviors, and improved overall health parameters. ¹¹⁴ , ¹¹⁵ , ¹¹⁶ This orientation serves as the framework for the recommendations to follow (see Table 3).

TABLE 3.

Potential solutions and associated policy frameworks to advance the receipt of quality oncologic care in rural populations.

Issue	Potential solutions/strategies	Federal/national policy frameworks, if available
Digital communications and telemedicine	Expand high‐speed internet access	Congressional legislation (such as the Broadband Equity, Access, and Deployment program)
	Telehealth	Medicare coverage of telehealth visits
Hospital access	Federal support for rural hospitals	Critical‐access (CA) hospitals
Regionalization of care	Facilitate relationships with large networks	Partnerships with the National Cancer Institute's (NCI's) Community Oncology Research Program
	Rural oncology home models
	Care coordination and hub‐and‐spoke models	Enhanced reimbursement through Medicare or other programs
Physician time and practice expenses	Improved reimbursement for time and practice expenses	Increase Medicare and Medicaid geographic practice cost indices for rural providers
Drug pricing	Subsidized drug pricing	Reform the 340B Drug Pricing Program
		Assign the 340B Drug Pricing Program to individual patients who meet indigency criteria, rather than to an institution
Specialty care	Traveler model
Physician compensation and reimbursement	Loan‐forgiveness programs	Expand the National Health Service Corps Rural Community Loan Repayment Program to also include oncology
	Provide facilities at subsidized rates
Emergency care	Ensure the availability of emergency care	CA hospitals; for non‐CA hospitals, identify a mechanism to facilitate the support of emergency care (i.e., oncology medical home model)
Biomarker testing and next‐generation sequencing	Enhanced use of digital communications to facilitate genomic tumor board interactions using a hub‐and‐spoke model to larger institutions
	Expanded data collection to enhance identification of treatment options	National Lung Cancer Roundtable model (expanded to include patient histories)
	Improved access to comprehensive tumor profiling	Create large‐scale network for comprehensive tumor profiling
Clinical trial participation	Promote the conduct of clinical trials in community, underserved, and rural sites	NCI's Community Oncology Research Program
	Application of decentralized clinical trial elements	US Food and Drug Administration Guidance (https://www.fda.gov/media/167696/download)
	Streamline trial eligibility	National working groups (American Society of Clinical Oncology/Friends of Cancer Research/US Food and Drug Administration joint task force)
	Patient education	National, advocacy, and institutional resources and programs
	Patient reimbursement to minimize or eliminate trial direct and indirect costs as a barrier to participation	US Food and Drug Administration guidance (https://www.fda.gov/regulatory‐information/search‐fda‐guidance‐documents/payment‐and‐reimbursement‐research‐subjects)

Digital communications and telemedicine

Modern digital and telecommunications tools could play a vital role in improving health care access for individuals from rural areas. Evidence from the conduct of clinical trials during the COVID‐19 pandemic provides a guide. Early in the pandemic, participation in cancer clinical trials dropped dramatically. ¹¹⁷ , ¹¹⁸ Patients with a cancer diagnosis reported being fearful of coming to clinics while the pandemic raged. ¹¹⁹ At the same time, staff at institutions were occupied with COVID‐19 cases, had themselves grown ill, or stayed home as a safety precaution. ¹²⁰ , ¹²¹ , ¹²² In response, major federal agencies provided guidance on how to mitigate trial procedures to better facilitate the conduct of trials during the pandemic. ¹²³ , ¹²⁴ These mitigation measures included the use of telemedicine for trial enrollment, remote monitoring of symptoms during treatment, and the local administration of protocol‐guided therapy. ¹²⁵ , ¹²⁶

The mitigation measures adopted during the pandemic align with the concept of decentralized clinical trials, a term intended to reflect the adoption of remote digital tools to ease the conduct of clinical trials for patients and providers who are not physically located at the center where the trial is being conducted. ¹²⁷ , ¹²⁸ , ¹²⁹ , ¹³⁰ Although many of these strategies have been considered for decades, the COVID‐19 pandemic forced their rapid adoption. Notably, their adoption early in the pandemic was associated with a rapid rebound in treatment trial enrollments, which returned to near pre‐COVID levels by the end of 2020 with little long‐term consequences for the integrity of trial conduct according to feedback from sponsors. ¹²⁵ , ¹³¹

The COVID‐19 experience provides broader lessons for how the quality of cancer care might be improved—and made more accessible—for individuals in rural areas. The potential promise of telemedicine was highlighted by the Institute of Medicine nearly 30 years ago. ¹³² The use of telemedicine has had substantial study in both national and international settings. ¹³³ , ¹³⁴ , ¹³⁵ , ¹³⁶ , ¹³⁷ , ¹³⁸ , ¹³⁹ , ¹⁴⁰ , ¹⁴¹ , ¹⁴² , ¹⁴³ , ¹⁴⁴ Models for telemedicine visits include direct patient contact with or without an accompanying interaction with a local clinician or, alternatively, through the use of nonreal‐time video communications or data transmissions. ¹³⁴ , ¹³⁹ Patients have commonly expressed satisfaction with telemedicine, including its convenience, efficiency, communication, privacy, and comfort. ¹³³ , ¹³⁵ , ¹³⁸ The effectiveness of telemedicine models in care delivery has been demonstrated for delivering psychiatric medications, emergency care, and trauma care. ¹³⁶ , ¹³⁷ , ¹⁴⁰

In cancer, tele‐oncology use was identified as superior to usual care for a range of patient quality‐of‐life outcomes, resulting in reduced depression and distress. ¹⁴⁵ It has been demonstrated that tele‐oncology models improve access to care and decrease health care costs. ¹³⁹ The routine use of telemedicine could help change the landscape of oncology care access for patients with cancer from rural areas. However, its use is constrained in two fundamental ways. First, digital medicine and tele‐oncology models are only as effective as the technology available at rural sites and in the homes of rural residents. Efforts to expand high‐speed internet access through Congressional legislation have been a necessary adjunct to building out capacity for telehealth models in rural areas. ¹⁴⁶ For instance, the 2021 Infrastructure Investment and Jobs Act included funding to create the BEAD (Broadband Equity, Access, and Deployment) program, which aims to provide funding to states to expand broadband access. ¹⁴⁷ , ¹⁴⁸ Such efforts will need to continue. Also, Medicare‐funded telehealth visits increased 63‐fold during the COVID‐19 pandemic, facilitated by Congressional approval of flexibilities around Medicare coverage of telehealth. ¹⁴⁹ These pandemic‐era flexibilities are at risk of being discontinued. ¹⁵⁰ Congress should aim to create consistent reimbursement models for telehealth consultations going forward.

Critical access hospitals

Critical access hospitals (CAHs) offer a valuable resource for addressing the needs of cancer patients living in rural areas. ¹⁵¹ The Centers for Medicare and Medicaid Services (CMS) designates CAHs as hospitals located in rural areas more than 35 miles from the nearest hospital or more than 15 miles in areas with mountainous terrain or only secondary roads. ¹⁵² They must maintain no more than 25 inpatient beds and an annual average length of stay of ≤96 hours per patient for acute inpatient care; furthermore, they must furnish 24‐hour emergency care services 7 days a week. The requirement for emergency care services is a key element for oncology care in rural areas because the cost of maintaining an emergency department and the difficulty of finding staff can otherwise be substantial.

CAHs represent over one half of all hospitals in rural communities. ¹⁵³ However, they are underused compared with CMS‐designated Prospective Payment System hospitals—which reimburse based on a predetermined, fixed amount—in both rural and urban areas. ¹⁵⁴ By using data from the American Hospital Association Annual Survey, Hung and colleagues demonstrated that, in 2017, the availability of chemotherapy services was notably lower among CAHs (27.5%) compared with rural (46.5%) or urban (64.5%) Prospective Payment System hospitals. ¹⁵³ Access to radiation services among CAHs was even lower (3.6% vs. 30.6% vs. 48.4%, respectively). Moreover, trends for both modalities were largely unchanged compared with the prior decade (2008). These findings highlight the limitations in specialized discipline and technical training required to provide oncology services in rural areas, a pattern that has persisted over time.

The regionalization of care

The ability of CAHs to provide oncology care services could be augmented by relationships with other provider institutions or by partnering with oncology practices to provide services, suggesting a role for improved regionalization of oncology care through shared care coordination. ¹⁵³ , ¹⁵⁵ One model could be partnerships with participating institutions in the NCI's Community Oncology Research Program (NCORP), which provides dedicated outreach to community institutions. ¹⁵⁶ This program also provides access to clinical trials for patients with cancer in rural areas. For instance, the University of Kansas Cancer Center has partnered with the Midwest Cancer Alliance to form a designated rural NCORP site, with the specific mission to increase participation in clinical trials for rural populations in Kansas. ¹⁵⁷ For one of the NCI's clinical trial networks, fully 19% of patients enrolled in clinical treatment trials over nearly 4 decades were from rural areas, demonstrating the reach of this trial program—as well as its predecessor program, the Community Clinical Oncology Program—outside urban centers. ³⁴ More generally, the increased application of digital telemedicine and communications strategies could allow interoperable relationships that would better facilitate combined services for rural patients with cancer. A recently proposed, community‐based rural oncology home model would aim to leverage advanced‐practice professionals, care coordination, and digital telehealth technologies to enhance the accessibility of specialized cancer care for rural patients. ¹⁵⁸

Another strategy is the hub‐and‐spoke model, which has particular application to rural areas. Under a hub‐and‐spoke model, a central hub facilitates the utilization of more complex care services not otherwise available at spoke sites, with patients at spoke sites receiving their basic care services locally and then directed to the central hub for fuller care. ¹⁵⁹ A hub‐and‐spoke model can also facilitate trial participation. An example is the New Mexico Cancer Care Alliance, which provides oncology care in underserved rural areas of New Mexico. The University of New Mexico Comprehensive Cancer Center, an NCORP member, serves as the central trial hub, and nine affiliate sites throughout the state are the spokes, with an emphasis on local customs and local needs, which are important in a state with a large minority population including approximately 40% Hispanic and 10% Native American. ⁴⁹ Similarly, a model that uses satellite clinics to main practices may be an effective way to extend trial participation to more rural areas. One example is the ONCare Alliance, a collaborative group of 33 independent, physician‐owned practices throughout the United States that serves local community patients. ¹⁶⁰ Because these models may only apply to sites within the same health care system or practices, adapting these models for cross‐system use could enhance their utility. ¹⁶¹

The hub‐and‐spoke model or other models for shared regionalization of care could be better supported through reimbursement for care coordination through future iterations of the CMS Oncology Care Model, such as its successor program, the Enhancing Oncology Model. ¹⁶² , ¹⁶³ These programs incentivize providers to improve cancer care coordination, ensure appropriate care, enhance the patient experience, and support decision making among providers and care settings. ¹⁶⁴ , ¹⁶⁵ These programs emphasize care coordination through physician–provider groups under the traditional Medicare fee‐for‐service provider model. Although some coordination services are reimbursable through Medicare billing claims, CAHs could not be reimbursed under the constraints of the Medicare payment system. ¹⁵³ , ¹⁶⁶ In the absence of this, payment mechanisms to encourage care coordination support for underserved rural hospitals and physician practice groups could serve to promulgate multiple avenues of shared care models across institutions and clinicians within regions.

Federal support for clinician time and practice expenses

Rural oncology practices with low patient volumes are barely able to maintain financial viability, with a median overall profit margin of 0.1% in 2017. ¹⁶⁷ Currently, Medicare and Medicaid geographic practice cost indices base medical reimbursement (for clinician time and effort and practice expenses) in part on cost‐of‐living factors, such as apartment rent in the area. ¹⁶⁸ , ¹⁶⁹ This has resulted in lower prices paid for medical services in underserved or rural communities. This pattern is further exacerbated by the higher prevalence of patients with Medicare and Medicaid in rural areas. Yet, even as reimbursement is often inadequate, the relative cost to clinical practices of providing comprehensive oncology care is routinely higher in rural communities, partly because there are no economies of scale. For instance, the capacity to provide and maintain the equipment required for radiation services depends on the number of patients served by a clinic and can be cost‐prohibitive if the volume is low.

The Medicare and Medicaid geographic practice cost indices are anticipated to be updated in 2026. ¹⁶⁸ We recommend recalibrating the indices to better reflect the financial challenges of providing oncologic care in rural areas.

Drug pricing

Drug pricing is a commonly cited burden for physicians who provide oncology services. ¹⁷⁰ The Public Health Service Act includes a provision in Section 340B mandating that drug manufacturers participating in Medicaid must sell outpatient drugs at discounted prices to specifically designated health care organizations that serve many uninsured and low‐income patients. ¹⁷¹ This provision is especially relevant to the needs of rural patients with cancer because it includes CAHs and rural referral centers. This program has been effective in promoting oncology programs in rural areas. One study indicated that rural hospitals newly enrolling in the 340B program were about twice as likely (17% vs. 9%, an absolute 8% increase) to add oncology services, although this effect predominantly occurred in states that adopted the ACA Medicaid expansion or had lower uninsurance rates. ¹⁷² As noted by Owsley and Bradley, the more limited increase in oncology services in socioeconomically vulnerable areas suggests that other programs could help support oncology service adoption. ¹⁷² Another possibility might be to assign 340B pricing to individual patients who meet indigency criteria rather than to an institution. This would allow any oncology practice, whether or not hospital‐based, to better serve indigent patients. Removing the ability of hospitals to use 340B drugs for fully insured patients would enhance the original intent of the law and curb the acquisition of oncology practices by hospitals.

Specialty care: The traveler model

For oncology clinicians, creating a sustainable practice in a rural setting can be both financially prohibitive and personally challenging. Medical professionals often emerge from school with large amounts of personal debt, which can exacerbate physician burnout. ¹⁷³ Physicians and advanced practice providers may be personally motivated to live in areas—especially urban areas—where raising a family is most convenient and can include opportunities for their spouses to find jobs and their children to attend adequately resourced school systems. Despite efforts to recruit physicians to rural areas with large sign‐on bonuses, medical school debt forgiveness, and other incentives, the resulting medical community is often unstable, lacking permanent oncology specialists. ⁴⁸ , ¹⁷⁰ , ¹⁷⁴

One approach to address this is a traveler model for oncology specialty care. Physicians working in underserved areas may be able to stay for a few days while other staff remain local. In a recent study examining the outreach of oncology professionals in rural areas, about one in four oncologists were characterized as having traveled to provide care, nearly one half of whom traveled with medium (from one to three outreach visits per month) or high (greater than three outreach visits per month) frequency. ¹⁷⁵ For patients, this resulted in an average reduction in travel time for chemotherapy and radiotherapy services of about 15 minutes per trip.

The traveler model can facilitate trial participation. The Missouri Baptist Medical Center facilitates improved rural participation in trials by sending medical oncologists to rural sites to support participation in trials. The oncologists provide training and support for local providers. In part because of these efforts, fully 36% of patients enrolled in their trials are from rural areas. ⁴⁹ , ¹⁷⁶ A visiting consulting clinics model in Iowa aims to staff local rural clinics with specialty oncology clinicians; under this model, local access to chemotherapy more than doubled. Internationally, as demonstrated in a systematic review, research into specialist outreach clinics in primary care and rural hospital settings in Australia indicated the potential to improve access and even outcomes. ¹⁷⁷ Mobile care services can enhance other elements of the cancer care continuum, such as cancer screening. The Ohio State University Comprehensive Cancer Center coordinates a mobile mammography program to bring mammography access to women living in rural areas of Appalachia. The program, which has screened thousands of women, includes screening and navigation services for women with abnormal findings on screening results. ⁴⁹

Physician compensation and reimbursement

Given the sparse and transitional nature of the rural oncology workforce, other approaches to compensation and reimbursement may be important to explore. Loan‐forgiveness programs, which are common for physicians locating to rural areas, could be both increased and indexed to time spent in the rural location. ¹⁷⁸ , ¹⁷⁹ , ¹⁸⁰ One possibility would be to expand disciplines eligible for the National Health Service Corps Rural Community Loan Repayment Program to also include oncology. Communities in need of physicians could provide the buildings and property for office space at subsidized rates or on lease‐to‐own terms if the physician stays for a minimum number of years. Removing the overhead cost of a practice facility could make it more attractive to live in a rural or underserved area. Owning property in an area could provide the economic incentive for a physician or group of physicians to commit to a durable stay. The establishment of a financially invested relationship with a community could foster a virtuous cycle of investment. With the advent of a stable medical community, demand for hospital services, such as laboratory or imaging services, will increase, further stabilizing hospital finances. Mechanisms to promote such measures are currently unknown and would depend on policymakers to explore. If any of these strategies are undertaken, in either small, pilot tests or larger scale efforts, mechanisms for program evaluation should be incorporated into their design to collect data and evaluate the performance of these models. Evaluations should aim to understand whether, and to what extent, outcomes are improved, including their potential for improving clinical trial enrollment.

Emergency care

CAHs are required to provide emergency services 24/7. This requirement is critical for providing oncology care in rural areas because the cost of maintaining an emergency department and the difficulty of finding staff can otherwise be substantial. For hospitals that are not designated as CAHs, however, a mechanism to support emergency care should be identified because emergency department services can reasonably be viewed as services contributing to the common good, such as fire or police departments, which are otherwise supported by local tax dollars. An oncology medical home model, in theory, may minimize the number of emergency department visits, hospital admissions, and readmissions. ¹⁸¹ , ¹⁸² , ¹⁸³ Providing the infrastructure and payments to a rural practice for these additional services may be a cost‐effective way to improve care without straining local resources.

Biomarker testing and next‐generation sequencing

Numerous studies have demonstrated that the use of biomarker testing and next‐generation sequencing to determine treatment for patients with cancer is less common in underserved areas. ¹⁸⁴ , ¹⁸⁵ , ¹⁸⁶ , ¹⁸⁷ , ¹⁸⁸ A systematic review and meta‐analysis indicated that patients with low socioeconomic status were 14% less likely to have predictive biomarker tests and 17% less likely to undergo biologic and precision therapy. ¹⁸⁸ These disparities are important because care determinations, in and outside of trials, are increasingly based on the genomics of the patient's cancer, including as they pertain to receiving immune‐targeted or molecular‐targeted therapies.

Physician factors could play an important role in reduced utilization among rural patients with cancer because oncologists are often challenged to maintain the day‐to‐day needs of the patients they serve, let alone keeping apprised of the rapidly evolving biomarker testing landscape that can point to a specific treatment for some cancers. Digital communications may offer one solution. A genomic tumor board consists of cancer genomic experts who assist oncologists in interpreting test results and identifying potential therapeutic strategies based on actionable targets. It is widely regarded as an effective educational and decision‐support tool and, with the aid of teleconferencing, could be of particular relevance to rural clinicians seeking treatment guidance. ¹⁸⁹ , ¹⁹⁰ , ¹⁹¹ Such a mechanism would be especially useful for sites already linked (say, thorough a hub‐and‐spoke model) to larger institutions. These interactive sessions with colleagues could support rural practices to choose appropriate treatments based on pertinent genomic data and the most up‐to‐date information in guidelines (such as the NCCN). Artificial intelligence software embedded in teleconferencing tools could be used to summarize discussions for documentation after review and confirmation by providers. The American Cancer Society, through the National Lung Cancer Roundtable, has conducted a series of state‐wide projects to expand clinicians' knowledge about biomarker testing for lung cancer using the American Cancer Society's Project ECHO model. ¹⁹² Such models could be extended to also include relevant data on patients' clinical histories to expand possible treatment options.

A key recommendation of the Cancer Moonshot Blue Ribbon Report was the idea of establishing a large‐scale network to offer patients comprehensive tumor profiling. ³ This proposed repository would enable patients to more readily participate in clinical trials to access the newest available treatments based on their genomic profile and immunotype. This idea was motivated, in part, by concerns about known disparities in access to comprehensive cancer testing and novel treatments, especially for those with limited socioeconomic means and rural populations. ¹⁸⁴ , ¹⁸⁵ , ¹⁸⁶ , ¹⁸⁷ , ¹⁸⁸ The emphasis of the Blue Ribbon Report was on participation in clinical trials because the penetration of genome‐driven oncology in practice at the time was limited. ¹⁹³ However, biomarker‐directed therapy has rapidly expanded in routine practice. Thus a registry of this kind could also be used to support cancer care options outside of trials and would have a particular benefit for underserved rural communities.

Trial participation: Access and eligibility

To help overcome the tyranny of travel distance for patients with cancer from rural areas and to find ways to better bring patients to trials, sponsors should more routinely provide the funds to travel to participate in a trial, including the costs related to housing, transportation, parking, and meals. ¹⁹⁴ , ¹⁹⁵ Pharmaceutical company‐sponsored trials, which represent a large majority of clinical treatment trials, provide travel support for patients in some instances. ³³ Offering financial assistance to patients who wish to participate in clinical trials is a crucial strategy for enhancing the geographic diversity of trial cohorts, one of the aims of the FDA's guidance to industry about improving diversity in clinical trials. ¹⁹⁶ One limitation is that specialized procedures, such as surgery, may need to be performed before participating in a study to meet eligibility criteria. Because these procedures are not included in the trial's specified therapies, any travel costs incurred for receiving pretrial procedures would not be covered by the trial sponsors.

Alternatively, the increased conduct of trials in community sites would satisfy the imperative to bring trials to the patients. Such efforts, as represented by the NCI's NCORP program (especially the minority‐underserved NCORPs), have been successful in generating representative enrollment of rural patients in federally sponsored trials. One study, representing over 40 years of enrollment to federally sponsored network group trials, demonstrated that the same proportion of individuals were from rural areas compared with the rural population in the United States. ³⁴

The application of decentralized clinical trial strategies will be vital for bringing trial participation opportunities to where patients live. Digital technology would bring the potential to improve access to trials for all patients and thereby to conduct trials more rapidly in more diverse sets of patients, including those from rural areas. Federal agencies and advocacy organizations have called for the increased use of decentralized clinical trial aspects to ease the participation of patients and providers. ¹⁹⁷ , ¹⁹⁸ , ¹⁹⁹ , ²⁰⁰ , ²⁰¹

Trial eligibility criteria often exclude patients with a higher burden of comorbid diseases. Therefore, improving access to clinical trials for individuals in rural areas, who tend to have a higher prevalence of non‐cancer health conditions, will partly depend on efforts to make these trials more inclusive and accommodating to patients with diverse health needs. A joint effort among the American Society for Clinical Oncology, the Friends of Cancer Research, and the FDA has resulted in recommendations to modernize eligibility criteria. ²⁰² The aim, in two cycles of effort, was to expand clinical trial access to individuals previously excluded from trials, including those with brain metastases, human immunodeficiency virus infection, organ dysfunction, prior malignancy, and poor performance status, among several other criteria. ²⁰² , ²⁰³ , ²⁰⁴ , ²⁰⁵ , ²⁰⁶ , ²⁰⁷ The recommendations have changed the way trial eligibility criteria are determined; one study indicated that trial eligibility criteria are now more inclusive of patients with brain metastases. ²⁰⁸ Ongoing efforts to design more inclusive clinical trials will enhance access for rural patients who have cancer. This improvement will also increase confidence that trial results are relevant to both rural and urban patients with cancer.

Clinical trial designs should prioritize patient convenience. This includes providing flexible follow‐up schedules to accommodate the demands of daily life and work in rural areas, where transportation options may be limited and taking time off work can be more difficult. Given a culture of mistrust of medical science, attempts to demystify participation in clinical trials are crucial. ²⁰⁹ This can be achieved through educational efforts aimed at informing health care providers and their patients as well as the families and friends of potential trial participants. ²¹⁰ Proactive educational efforts to help illuminate the nature of clinical trials could yield outsized benefits for patients who may consider trial participation a good option for their treatment and could help overcome mistrust, as well as lack of knowledge, about clinical trial participation. In part, this is relevant because many patients are simply not aware that a trial may be an option for their care, with one study indicating that 80% of patients were unaware that a clinical trial might be a possibility. ²⁹ , ²¹¹ Various organizations provide expertise and resources in this area, including governmental agencies like the NCI; advocacy organizations, including the American Cancer Society and the American Society of Clinical Oncology; large cancer centers; and nonprofit organizations (see Table S1). Beyond travel costs, both direct and indirect costs to patients of trial participation can be substantial. Patients facing socioeconomic challenges are less likely to participate in trials than those without such challenges, with multiple studies demonstrating that lower income patients were 30% less likely to participate in clinical trials than higher income patients. ⁸⁷ , ²¹² , ²¹³ , ²¹⁴ Thus clinical trial designers should minimize cost by adopting more pragmatic trial designs and procedures, and sponsors should help support the economic cost to the patient for trial participation. A common reason for not reimbursing patients in trials is to prevent undue influence on treatment decisions, as stated in the US Common Rule for the Protection of Human Subjects. Concerns exist that financial incentives could distort perceptions of risks and judgments. However, the FDA has articulated the position that paying research subjects to participate in studies is an acceptable practice in general. ²¹⁵ Several models about how to reimburse patients for trial participation that would alleviate concerns about undue influence have been proposed. These include a reimbursement model, wherein patients are reimbursed for their actual expenses; and a wage‐payment model, which aims to financially compensate patients for their time, effort, discomfort, and study contributions. ²¹⁶ Under any payment mechanism, the ultimate aim is to remove ancillary costs as a factor in patient decision making. ¹⁹⁴

Despite the challenges of conducting trials in rural areas, the establishment of a research culture within rural communities may have benefits that extend to aspects of rural living beyond the treatment of a single disease. These may include increased economic activity, improved health behaviors, and improved overall health parameters. ¹¹⁴ , ¹¹⁵ , ¹¹⁶ Viewed in this context, the improved conduct of clinical trials in rural areas brings full circle the predicate that the conduct of cancer clinical trials is an integral element of the delivery of quality oncologic care to rural communities.

CONCLUSION

This review highlights issues around access both to cancer clinical trials and to quality oncologic care in rural areas. Our premise was that the best treatment is received in a clinical trial, and the ability to participate in clinical trials also reflects the ability to adopt new clinical trial findings and to provide high‐quality care in rural communities. Ideally, clinical trials should be available where patients routinely receive their oncologic care. Providing access to clinical trials requires a strong medical ecosystem and the ability to provide oncologic care locally. Efforts to resolve these disparities must recognize that the application of efficiency and scale—a hallmark of market forces—will, on its own, be inadequate because the same level of oncology care services is required even when patient volume is lower. Nevertheless, the equitable distribution of health care between urban and rural areas may bring mutual benefits that market metrics cannot readily quantify. If rural patients with cancer can receive care close to home, they may experience less stress and greater trust. Cancer care information may be more efficiently distributed, improving community understanding of medical science. Health care dollars would be retained in rural communities rather than transferred to urban centers, improving economic and health resilience for communities. Participation in clinical trials close to home would spread the message that rural citizens have the opportunity to receive the same cutting‐edge treatments as their urban counterparts. Taken together, these factors could create a virtuous cycle of mutual benefit to help bridge rural and urban communities. Thus, providing quality oncology care to rural patients with cancer is not just an ethical and moral imperative but could also bring cultural and sociopolitical benefits and should be a priority for policymakers.

CONFLICT OF INTEREST STATEMENT

Joseph M. Unger reports personal/consulting fees from the American Cancer Society, the Laura and John Arnold Foundation, and Loxo Oncology outside the submitted work. Raymond U. Osarogiagbon reports personal/consulting fees from AstraZeneca; and stock ownership in Bridge BioPharma, Eli Lilly and Company, Gilead Sciences (aka Gilead Foundation), Immunocore, and PFIZER CANADA INC. outside the submitted work. Barbara L. McAneny disclosed no conflicts of interest.

Supporting information

Table S1

Unger JM, McAneny BL, Osarogiagbon RU. Cancer in rural America: improving access to clinical trials and quality of oncologic care. CA Cancer J Clin. 2025;75(4):341‐361. doi: 10.3322/caac.70006