Individuals from rural populations make up approximately 15% of the US population and face distinct health care challenges in comparison with individuals who live in metropolitan regions.1 Previous studies have demonstrated that rural patients with cancer experience worse survival, with the largest disparities observed for lung, colorectal, prostate, and cervical cancers.2 It has been posited that adverse outcomes among rural cancer patients arise from complex interactions between disease biology, delayed diagnoses, stage, treatment, health literacy, socioeconomic status, and other factors involving access to care. Investigators have proposed using multilevel models to examine and explain these disparities.3 Despite numerous studies addressing these issues in large cohorts and institutional settings, limited information exists regarding outcomes among rural patients with thorough assessment of clinical, demographic, and survival data across cancer sites.
In their article “Geographic Distribution and Survival Outcomes for Rural Patients With Cancer Treated in Clinical Trials,” Unger and colleagues adeptly use a large clinical trial database of 36 995 patients enrolled in phase 2/3 or phase 3 SWOG treatment trials from 1986 to 2012 to better understand cancer disparities in the context of geography.4 The novel study design provides distinct advantages, including comprehensive coverage (all 50 states), diversity of cancer sites, and standardized treatment regimens—informing disparities between rural and urban patients with cancer across the continuum of care. Surprisingly, rural status was not a predictor of worse outcomes at nearly all cancer sites, and results were consistent regardless of how rural status was defined. The authors demonstrate that rural and urban patients with cancer experience similar outcomes when receiving treatment in the context of randomized clinical trials. These data suggest that receipt of guideline-driven cancer care, as provided in clinical trials, may be a feasible approach to eliminate the cancer survival disparities between rural and urban patients.
While the study findings show that patients from rural settings do not have worse disease survival than their urban counterparts, as has been previously postulated,5 there are concerns around selection bias (lack of external validity). The current study did not account for other important barriers that potentially contribute to disparities between rural and urban patients with cancer, including limited access to screening, higher prevalence of poor prognostic factors and comorbid conditions, limited access to specialized care, educational barriers, and transportation challenges.6,7 Additionally, patients from rural areas commonly have lower incomes and higher rates of poverty when compared with patients from metropolitan settings,8 exacerbating health disparities. Clinical trials are often conducted among a select group of eligible patients who must both be invited to participate and accept participation. The aforementioned factors could be associated with selection (ie, access to cancer centers engaged in clinical trials and comorbid conditions) and acceptance (ie, financial, educational, and transportation barriers), and these factors are known to differ geographically. The study design, while minimizing differences by treatment regimens, may mask the causal role of these other factors mediating disparities between rural and urban patients by creating comparison populations that are essentially homogeneous for these factors. Thus, the absence of survival differences by geography in the clinical trial setting should not be interpreted to indicate that differences do not exist in other contexts.
It remains unknown whether the study findings result from (1) all patients receiving the types of standard-of-care therapy involved in both groups of a randomized trial; (2) patients receiving highly specialized treatments that improve on the standard of care; or (3) features of the patient and caregiver population that permit travel from a rural environment to access cancer centers engaged in clinical trials. Additional analyses with individual patient-level data on income, socioeconomic status, detailed treatment regimen, treatment intensity, adherence, and outcomes in population-based cohorts with cancer are necessary to elucidate strategies for improving survival for rural patients more broadly. Stratification by (rather than adjustment for) race and gender may also be informative for the design of future interventions and planning care.
Finally, the current study was centered on the first 5 years after registration to focus on cancer-related and treatment-related survival. Although the study authors allowed for time variation between 1 and 10 years to account for differential prognostic patterns by cancer site, it remains unclear whether differences in survival between rural and urban patients are observed beyond these terms. Because of improvements in screening and treatment, many cancer survivors are expected to live well beyond 5 years following a cancer diagnosis. Thus, disparities in survival between rural and urban patients farther along in the postdiagnostic period also are of interest for future planning and resource allocation.
Despite these challenges, this research sheds light on an important clinical issue. Previous studies have shown that rural patients do not receive standard-of-care therapy at as high a rate as their metropolitan counterparts.9 Distal factors related to standard of care (ie, policies, shared social norms, socioeconomic disadvantage, and availability of health services) operate at the population level10 and may be difficult to address because of the scarcity of resources in areas with few people. This study suggests that congruent therapy in rural and urban settings may, in part, improve survival disparities in cancer. Clinicians and cancer health policy specialists may use these data to inform practice and develop comprehensive cancer care and cancer survivorship planning programs to address the need of rural patients with approaches that use standardized protocol-driven care. These interventions also must be evaluated within the context of randomized trials. Additional efforts should be undertaken to understand the institutional, social, and physical barriers to health equity for rural patients with cancer in population-based studies.
Published: August 17, 2018. doi:10.1001/jamanetworkopen.2018.1243
Correction: This article was corrected online September 14, 2018, for errors in the text.
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2018 McCullough LE et al. JAMA Network Open.
Corresponding Author: Christopher R. Flowers, MD, MS, Lymphoma Program, Emory University, 1365 Clifton Rd, NE Bldg B, Ste 4302, Atlanta, GA 30322 (email@example.com).
Conflict of Interest Disclosures: Dr Flowers has served as a consultant for Abbvie, AstraZeneca, Bayer, BeiGene, Celgene (unpaid), Denovo Biopharma, Genentech/Roche (unpaid), Gilead, OptumRx, Karyopharm, Pharmacyclics/ Janssen, and Spectrum and has received research funding from Abbvie, Acerta, BeiGene, Celgene, Gilead, Genentech/Roche, Janssen Pharmaceutical, Millennium/Takeda, Pharmacyclics, TG Therapeutics, Burroughs Wellcome Fund, Eastern Cooperative Oncology Group, National Cancer Institute, and the V Foundation. Dr McCullough has served as a consultant for Advanced Health Solutions, LLC and has received research funding from the AVON foundation and the V Foundation.
Funding/Support: Research reported in this publication was supported in part by National Cancer Institute award number K24CA208132 to Dr Flowers.
Role of the Funder/Sponsor: The National Cancer Institute had no role in the preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
McCullough LE, Flowers CR. Identifying and Addressing Disparities in Survival Outcomes for Rural Patients With Cancer. JAMA Netw Open. 2018;1(4):e181243. doi:10.1001/jamanetworkopen.2018.1243
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