Economic Burden NSCLC: A Systematic Review of Healthcare Costs and Resource Utilization

A recently published systematic literature review synthesizes evidence from 50 publications across 43 studies on the economic burden NSCLC in locally advanced (stage IIIB/C) and metastatic (stage IV) non-small cell lung cancer, highlighting high healthcare resource utilization (HCRU) rates including hospitalizations (13.0%–98.2% of patients), emergency department (ED) visits (2.5%–83.1%), outpatient visits (74.6%–100.0%), and diagnostic tests (45.9%–92.0%). Mean direct costs varied widely from US$5,647 in Brazil to US$158,908 in the US over 12–24 months, driven primarily by drug costs (9.5%–76.0%), outpatient services (39%–70.6%), and inpatient care (5.0%–58.1%), with immunotherapy linked to lower HCRU and costs compared to chemotherapy. Brain/central nervous system (CNS) metastases emerged as the predominant clinical driver of elevated HCRU and costs, alongside disease severity, targeted therapies, chemotherapy, and comorbidities.

Metastases Fuel Skyrocketing HCRU

Patients with advanced NSCLC exhibited consistently high HCRU, with hospitalization rates peaking at 98.2% over 11–24 months, particularly in the US, Japan, and South Korea, where mean lengths of stay reached 16.4 days and admissions hit 2.8 per patient annually; these were notably lower with immunotherapy (e.g., 43.8% vs. 58.2% for chemotherapy in first-line therapy) due to reduced adverse events and treatment administration needs. ED visits affected up to 83.1% of patients over 8–12 months, highest in Brazil, the US, and Taiwan, while outpatient visits neared universality (up to 100% in France, Spain, Taiwan, and Japan), with means of 34.4–48.0 in the US over 2–12 months; diagnostic tests like imaging were used by 83.6%–92.0%, with intensive care unit admissions low except in Brazil (8.6%). Brain/CNS metastases significantly amplified utilization—e.g., 67.1% vs. 57.1% hospitalization rates (p<0.05)—and immunotherapy consistently reduced these metrics relative to chemotherapy across lines of therapy, underscoring a shift toward less resource-intensive care pathways. These patterns affirm brain/CNS metastases as the primary clinical escalator of HCRU.

PRISMA-Guided Synthesis of Global Evidence

The review adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, screening Embase and MEDLINE from 2011 onward via a predefined protocol targeting HCRU (hospitalizations, ED/outpatient visits, intensive care unit admissions, tests) and costs (direct medical/non-medical, indirect, out-of-pocket), supplemented by oncology conference proceedings and gray literature; a single reviewer extracted data from prioritized moderate-to-good quality studies (Newcastle-Ottawa Scale ≥5/9), with qualitative synthesis due to heterogeneity in currencies, follow-up (8–24 months), and reporting. Studies (n=43 unique) spanned the US, Europe (e.g., Germany, UK, Italy), Asia (Japan, Korea, China, Taiwan), and others, focusing on subgroups like treatment line, metastases, and mutations (e.g., epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK]); limitations included no meta-analysis, single-reviewer extraction (quality-checked), and incomparability from diverse healthcare systems. This rigorous, descriptive approach provides a credible foundation for interpreting cost disparities.

HEOR Strategies to Offset NSCLC Costs

The findings underscore advanced NSCLC’s profound economic burden—up to 0.133% of gross domestic product in some nations—with US costs 28-fold higher than Brazil’s, driven by inpatient/outpatient dominance and immunotherapy’s cost offsets (e.g., €19,663.9 vs. €127,134.2 for second-line chemotherapy in Spain), positioning immune checkpoint inhibitors as reimbursement-favorable for reducing HCRU in market access dossiers. Brain/CNS metastases inflate costs 1.77-fold (e.g., US$44,692 vs. US$32,230 in Korea; p<0.0001), necessitating targeted pricing models that prioritize biomarker-driven therapies (e.g., EGFR/ALK testing to curb hospitalization durations of 9 vs. 4 days in first-line). Indirect costs (US$1,413 in China) and out-of-pocket burdens (€5,691 patient/€4,125 caregiver in Europe) highlight equity gaps, urging reimbursement policies incorporating productivity losses for low/middle-income contexts. Broader trends toward next-generation sequencing and low-dose computed tomography screening could avert progression-related escalation, enhancing cost-effectiveness in outcomes research and supporting premium pricing for therapies mitigating metastases-driven burden, ultimately optimizing resource allocation across global systems.