Established and Emerging Less Invasive Biomarkers and Technologies for Lung Cancer Screening: Puerto Rican Context.
Authors
Affiliations (4)
Affiliations (4)
- Pharmaceutical Sciences Department, School of Pharmacy, University of Puerto Rico, Medical Sciences Campus, San Juan, PR 00936, USA.
- School of Naturopathic Medicine, Universidad Ana G. Mendez Gurabo Campus, Gurabo, PR 00778, USA.
- Biology Department, University of Puerto Rico, Cayey Campus, Cayey, PR 00736, USA.
- Biochemistry & Pharmacology Department, San Juan Bautista School of Medicine, Caguas, PR 00726, USA.
Abstract
In Puerto Rico (PR), lung cancer mortality remains high because diagnoses frequently occur at advanced stages. Although low-dose computed tomography (LDCT) lowers lung cancer-specific mortality, this screening is difficult to operationalize locally due to high false-positive rates, radiology capacity constraints, payer limitations, and geographic barriers affecting rural populations. We performed a narrative review on the literature from 2001-2026 of established and emerging detection strategies-LDCT; serum biomarkers (CEA, CYFRA-21-1, NSE, ProGRP, SCC-Ag, HE4, Hp, TAAb); breath analysis (FeNO and VOCs); and liquid biopsy (ctDNAs/CTCs/miRNAs). We assessed technical performance, feasibility, and health-system fit in PR and then synthesized these findings into an implementable biomarker-first triage workflow for are. Multiplex serum panels analyzed with machine learning outperform single markers and TAAb provide high specificity with biological lead time, supporting their use as a triage gateway before LDCT. Breathomics is also feasible at the point of care. Liquid biopsy has modest sensitivity in very-early disease yet provides molecular adjudication for indeterminate nodules. A stepwise pathway-expanded risk assessment, integrated multi-panel testing in primary care, LDCT reserved for biomarker-positive individuals, and liquid biopsy when imaging is inconclusive-can enrich pre-test probability, reduce unnecessary scans, align with capitation, and protect limited radiology capacity. An integrated, non-invasive, biomarker-first triage model offers a pragmatic, equitable route to earlier lung cancer detection in PR and resource stewardship, while reducing disparities.