Rural-Urban Disparities in Contemporary Systemic Therapy for Advanced Prostate Cancer

Abstract

This cross-sectional study examines the associations of rural-urban residence and race with receipt of systemic therapy for advanced prostate cancer.

Introduction

Contemporary systemic therapies added to androgen deprivation monotherapy improve survival in advanced prostate cancer (PC), but access may be constrained by geography and structural barriers.^1,2,3 Prior studies have documented racial disparities in PC treatment but have been limited by older therapeutic eras and regional datasets, and, to our knowledge, none has examined whether racial disparities in receipt of contemporary systemic therapy are modified by rural-urban residence.⁴ We hypothesized that rural residence and Black race would each be independently associated with lower receipt of contemporary systemic therapy and that these disparities would be amplified among Black men in rural areas.

Methods

This cross-sectional study was approved by the Brigham and Women’s Hospital institutional review board (No. 2019P000756) with a waiver of informed consent because we used deidentified Medicare data. This study is reported following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cross-sectional studies. Using complete traditional Medicare fee-for-service claims from January 1, 2018, through December 31, 2022, we identified male beneficiaries with advanced PC, including those with metastatic castration-sensitive, nonmetastatic castration-resistant, and metastatic castration-resistant PC, using a validated claims-based algorithm based on androgen deprivation therapy initiation or bilateral orchiectomy, excluding men receiving curative radiation therapy around cohort entry.⁵ The primary outcome was receipt of contemporary systemic therapy within 12 months of cohort entry, defined as taxane chemotherapy, second-generation androgen receptor pathway inhibitors, or poly–ADP-ribose polymerase inhibitors from Medicare Parts B and D claims, designed to capture guideline-concordant systemic therapy intensification beyond androgen deprivation monotherapy across the spectrum of advanced PC. Primary exposures were geographic residence, categorized as metropolitan, urban, or rural using 2023 Rural-Urban Continuum Codes, and race and ethnicity, derived from the Medicare Beneficiary Summary File. Details are provided in the eMethods in Supplement 1.

Descriptive statistics portrayed national utilization. Multivariable logistic regression model assessed associations of residence and race with treatment receipt, adjusting for sociodemographic factors. Association modification by residence was further assessed using race × residence interaction terms. SEs were clustered at the hospital referral region level to account for regional correlation in treatment patterns. Analyses were performed from September to December 2025 using SAS version 8.3 (SAS Institute), with 2-sided P < .05 indicating significance.

Results

We included 44 047 men (mean [SD] age, 78.27 [8.90] years) with advanced PC; 10 228 men (23.2%) received contemporary systemic therapy. Therapy receipt varied across hospital referral regions, ranging from 4.3% to 48.0% (Figure). In the multivariable model, men residing in rural areas had lower odds of therapy receipt (odds ratio [OR], 0.79; 95% CI, 0.72-0.88), as did men from urban areas (OR, 0.87; 95% CI, 0.79-0.95), compared with metropolitan areas. Black men had lower odds of receiving contemporary systemic therapy compared with White men (OR, 0.82; 95% CI, 0.75-0.89) (Table). In the model including race × residence interaction terms, racial differences were modified by geographic residence (Table). Among men from rural areas, Black men had lower odds of receiving contemporary systemic therapy compared with White men (OR, 0.64; 95% CI, 0.50-0.82). Similarly, in metropolitan areas, Black men had lower odds of treatment receipt than White men (OR, 0.83; 95% CI, 0.75-0.91). No statistically significant racial difference was observed among men living in urban areas.

Figure. Map of Utilization of Contemporary Systemic Therapy for Advanced Prostate Cancer by Hospital Referral Region (HRR).

Contemporary systemic therapy was defined as treatment with taxane chemotherapy, second-generation androgen receptor pathway inhibitors, or poly–ADP-ribose polymerase inhibitors, identified from Medicare Parts B and D claims. HRRs are geographic units defined by patterns of referral for tertiary care and represent regional health care markets.

Table. Adjusted Odds of Receipt of Contemporary Systemic Therapy Among Medicare Beneficiaries With Advanced Prostate Cancer.

Model	OR (95% CI)a	P value
Residence type
Metropolitan	1 [Reference]	NA
Rural	0.79 (0.72-0.88)	<.001
Urban	0.87 (0.79-0.95)	<.001
Race and ethnicity
Black	0.82 (0.75-0.89)	<.001
White	1 [Reference]	NA
Otherb	1.01 (0.92-1.24)	.82
Race × residence interaction (reference: White)c
Black, metropolitan	0.83 (0.75-0.91)	<.001
Black, urban	0.90 (0.73-1.11)	.32
Black, rural	0.64 (0.50-0.82)	<.001

Abbreviations: NA, not applicable; OR, odds ratio.

^a Odds ratios were estimated using multivariable logistic regression models evaluating receipt of contemporary systemic therapy within 12 months of cohort entry. All models adjusted for age at diagnosis, year of cohort entry, Charlson Comorbidity Index, dual Medicare-Medicaid eligibility, disability status, and US Census region.

^b Includes Asian, Hispanic, North American Native, and other races and ethnicities encoded by the Medicare Beneficiary Summary File.

^c Overall P for interaction < .001.

Discussion

In this cross-sectional study including a national cohort of Medicare beneficiaries with advanced PC, fewer than one-quarter received contemporary systemic therapy. Rural residence and Black race were each associated with lower odds of treatment receipt, with the largest disparities observed among Black men living in rural areas. These findings highlight compounded inequities at the intersection of race and geography in access to contemporary, life-prolonging systemic therapies for advanced PC.

The disparities we document reflect structural inadequacies in the US health care system. Nonmetropolitan areas are projected to reach only 29% of adequate oncology workforce capacity by 2037, a consequence of chronic underinvestment in rural health care infrastructure.⁶ Racial disparities reflect the enduring legacy of structural racism, including residential segregation that independently is associated with worse PC outcomes for Black men, and persistent barriers to specialty care access that remain even after accounting for insurance status.¹ Notably, studies in equal-access settings demonstrate equivalent outcomes between Black and White patients with PC, confirming that observed disparities are impacted by unequal access.³ Black men in rural areas face the compounding of both structural burdens, explaining the amplified disparities in our interaction analysis. Addressing these inequities will require targeted policy interventions in workforce distribution, rural health care infrastructure, and the structural determinants of racial inequity in cancer care.

This study has limitations. Medicare claims lack detailed information on disease burden and patient preferences. Findings may not generalize beyond Medicare beneficiaries and may contain unmeasured confounding, such as site of care. Small proportions of men receiving androgen deprivation therapy for biochemical recurrence may be captured within our cohort, and men receiving radiation for oligometastatic disease may have been excluded. However, neither is expected to differ systematically by race or rural-urban residence. Additionally, lutetium-177-PSMA-617 radioligand therapy was excluded because of recent approval.⁷ Radium-233 and sipuleucel-T were excluded because of low contemporary use to enhance the specificity of outcome definition.

Supplement 1.

eMethods.

Supplement 2.

Data Sharing Statement