Medication Burden Linked With Acute Care Use in ARSI-Treated Prostate Cancer

Medication burden, characterized by polypharmacy and suboptimal treatment adherence, is a predictor for acute care use among older patients with metastatic prostate cancer being treated with androgen receptor signaling inhibitors (ARSIs), according to a new observational study in Cancer.¹

In patients prescribed oral ARSIs abiraterone (Zytiga; Yonsa), enzalutamide (Xtandi), or apalutamide (Erleada), both polypharmacy and ARSI nonadherence were independently associated with acute care use, defined as any inpatient hospitalization or emergency visit within 6 months of ARSI initiation. These associations are described by respective incidence rate ratios of 1.59 (95% CI, 1.28–1.98) with polypharmacy and 2.50 (95% CI, 2.00–3.03) with treatment nonadherence, suggesting that these factors are predictors of increased risk of acute care use in this population.

Notably, polypharmacy, defined as having 8 or more medications, was present in about half (50.6%) of patients prior to ARSI initiation, and the ARSI nonadherence rate after 6 months of initiation was 34.0%. A difference in nonadherence rate was observed between those with polypharmacy and those without polypharmacy (34.9% vs 33.1%), but this difference was not significant (P =.34).

“Ultimately, this study highlights a need and opportunity for more individualized and interdisciplinary care in managing medication burden in older patients with metastatic prostate cancer,” the authors, Liu et al, concluded.¹

Study Design and Patient Characteristics

The study employed a retrospective design, drawing from the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database containing claims and prescription data of patients.

The analysis included a total of 2697 patients with metastatic prostate cancer aged 66 years and older who had at least 1 prescription of an oral ARSI (abiraterone, enzalutamide, or apalutamide) between 2010 and 2017. In the total patient population, 76.2% (n = 2056) were prescribed abiraterone, and 71.8% (n = 1938) were prescribed enzalutamide or apalutamide. The median age of the population was 75 years, and the majority of patients were White (80.3%).

Other than the inherent limitations of a retrospective study in establishing causation, the authors also cited database limitations which restricted their capacity to conduct certain analyses. For instance, the SEER-Medicare database does not have sufficient information capturing “upstream” factors such as social determinants of health, health literacy, and structural inequalities, limiting the ability to examine and adjust for these factors in the analysis. Further, the authors noted they were unable to stratify by therapeutic class to account for known interactions between ARSIs and other drug classes, which could also potentially influence the results.

Finally, the overrepresentation of White patients in this study limited statistical power to detect racial differences; as such, the results may not be as generalizable to the experiences of patients with other races.

Reducing Acute Care Use: Intervention Strategies

Androgen deprivation therapy combined with ARSIs is an emerging management practice for patients with metastatic prostate cancer. However, the complexity of treatment may prove challenging for older patients who increasingly face more comorbidities as they age and require concurrent medications.² This polypharmacy burden may ultimately heighten their risk for adverse events, which in turn may prompt greater acute care utilization.

Given the associations observed, the authors outlined potential intervention strategies to reduce acute care use through addressing both polypharmacy and medication adherence. Specifically, they placed an emphasis on early preventative approaches, addressing polypharmacy early on in ARSI treatment as well as addressing barriers to ARSI adherence through treatment plan consolidation and improved patient-provider communication.

“Addressing polypharmacy alongside the initiation of prostate cancer directed therapy might prevent downstream acute care use,” explained the authors.¹ “Improving medication adherence through [patient] education, access, and care coordination can enhance outcomes in the older adult population.”

REFERENCES

1. Liu MA, Raghunathan R, Runcie K, et al. Association between medication burden and acute care use in older metastatic prostate cancer patients on androgen receptor signaling inhibitors. Cancer. 2025;131(21):e70163-e70163. doi:10.1002/cncr.70163

2. Doumat G, Daher D, Itani M, et al. The effect of polypharmacy on healthcare services utilization in older adults with comorbidities: a retrospective cohort study. BMC Prim Care. 2023;24(1). doi:10.1186/s12875-023-02070-0