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Comparative Study
. 2018 Aug 3;1(4):e181235.
doi: 10.1001/jamanetworkopen.2018.1235.

Geographic Distribution and Survival Outcomes for Rural Patients With Cancer Treated in Clinical Trials

Affiliations
Comparative Study

Geographic Distribution and Survival Outcomes for Rural Patients With Cancer Treated in Clinical Trials

Joseph M Unger et al. JAMA Netw Open. .

Abstract

Importance: Studies showing that patients with cancer from rural areas have worse outcomes than their urban counterparts have relied on cancer population data and did not account for differences in access to care. Clinical trial patients receive protocol-directed care by design, so large clinical trial databases are ideal for examining the impact of rural vs urban residency on outcomes.

Objective: To compare the geographic distribution and survival outcomes for rural vs urban patients with cancer treated in clinical trials.

Design, setting, and participants: In this comparative effectiveness retrospective cohort analysis, 36 995 patients from all 50 states enrolled in 44 phase 3 and phase 2/3 SWOG (formerly the Southwest Oncology Group) treatment trials from January 1, 1986, to December 31, 2012, were examined. Seventeen different cancer-specific analysis cohorts were constructed. Data through January 30, 2018, were analyzed.

Main outcomes and measures: Rural vs urban residency was defined using the Rural-Urban Continuum Codes developed by the US Department of Agriculture. Multivariate Cox regression was used to estimate the association of residency with overall survival, progression-free survival, and cancer-specific survival, controlling for major disease-specific prognostic factors and demographic variables and stratifying by study. Different definitions of rurality were examined. The distribution of rural vs urban patients by geographic region was described.

Results: Overall, 27.7% of patients were 65 years or older (range across 17 cohort analyses, 7.8%-74.5%), 40.3% were female in the non-sex-specific analyses (range across 17 cohort analyses, 28.1%-45.9%), and 10.8% were black (range across 17 cohort analyses, 1.9%-22.4%). Overall, 19.4% of patients (7184 of 36 995) were from rural locations. Rural patients were more likely to be aged 65 years or older (rural, 30.7% aged ≥65 years vs urban, 27.0% aged ≥65 years; difference, 3.7%; 95% CI, 2.5%-4.9%; P < .001), were less likely to be black (rural, 5.4% vs urban, 12.1%; difference, 6.7%; 95% CI, 6.1%-7.3%; P < .001), were similar with respect to sex (rural, 40.4% female vs urban, 39.7% female; difference, 0.6%; 95% CI, -1.4% to 2.6%; P = .53), and were well represented within major US geographic regions (West, Midwest, South, and Northeast). Clinical prognostic factors were similar. In multivariable regression, rural patients with adjuvant-stage estrogen receptor-negative and progesterone receptor-negative breast cancer had worse overall survival (hazard ratio, 1.27; 95% CI, 1.06-1.51; P = .008) and cancer-specific survival (hazard ratio, 1.26; 95% CI, 1.04-1.52; P = .02). No other statistically significant differences for overall, progression-free, or cancer-specific survival were found. Results were consistent regardless of the definition of rurality.

Conclusions and relevance: Rural and urban patients with uniform access to cancer care through participation in a SWOG clinical trial had similar outcomes. This finding suggests that improving access to uniform treatment strategies for patients with cancer may help resolve the disparity in cancer outcomes between rural and urban patients.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Unger reported grants from the HOPE Foundation and the National Cancer Institute during the conduct of the study. Ms Moseley reported other support from the National Cancer Institute during the conduct of the study. Dr Chavez-MacGregor reported employment in MD Anderson Physician’s Network, consulting or advisory roles for Pfizer and Roche/Genentech, research funding from Novartis, and travel funding from Pfizer. Dr Ramsey reported consulting or advisory roles for Bayer, Bristol-Myers Squibb, Genentech, Kite Pharma, and Seattle Genetics; research funding from Bayer and Bristol-Myers Squibb; and travel funding from Bayer Schering Pharma, Bristol-Myers Squibb, and Flatiron Health. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Map Showing 36 995 SWOG Enrollments From 1986 to 2012 by Rural vs Urban County Origin
The percentage of total SWOG and US cancer population cases by region are shown in the table, along with the estimated proportion in rural areas for each region.
Figure 2.
Figure 2.. Forest Plot Showing the Association of Rural Residence and Survival Outcomes From Cox Regression Analyses
Results are grouped by adjuvant vs advanced disease and ordered in ascending order of the overall survival hazard ratio (HR). Each horizontal bar represents the 95% confidence interval for the associated HR (box). Hazard ratios to the left of the line of equal hazard indicate better survival for rural patients, and HRs to the right of line of equal hazard indicate worse survival for rural patients. ER indicates estrogen receptor; PR, progesterone receptor.
Figure 3.
Figure 3.. Association of Rural Residency and Overall Survival for Different Cut Points of Rural-Urban Continuum Codes
The z scores (each represented by a circle) reflect the strength and direction of the association of residence and overall survival for each combination of Rural-Urban Continuum Code cut point (8 different cut points) and follow-up time (1-10 years) across the panel of 17 cancer cohorts. Negative z scores reflect better outcomes for rural patients; positive z scores reflect worse outcomes for rural patients. The dark gray line connects the mean values for each cut point. The blue horizontal lines show 2-tailed critical α levels for P = .05 and P = .01 (representing an informal adjustment for multiple comparisons), and the orange horizontal lines show 2-tailed critical α levels for P = .006 (representing a Bonferroni adjustment for multiple [n = 8] comparisons).

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