Strategies to enhance drug retention after intratumoral and locoregional therapy: A scoping review

The effectiveness of intratumoral and locoregional therapies depends on achieving and maintaining therapeutic drug concentrations within tumors. Intratumoral therapy refers to direct injection into tumor tissue, locoregional therapy refers to delivery confined to a tumor-bearing region, and retention refers to persistence of the administered agent within the tumor over time. Retention is distinguished from initial delivery, accumulation, penetration, spatial distribution, and therapeutic efficacy. We conducted a PRISMA-ScR-guided scoping review to map strategies that enhance local retention or exposure after intratumoral or locoregional administration and classify them by principal mechanism. Two investigators independently screened records; 125 records were identified, 100 remained after duplicate removal, 84 full-text reports were assessed, and 73 studies were included. The finalized charting fields were citation, model/population, intervention strategy, principal evidence group, key retention/local-exposure finding, translational stage, and evidence classification. Studies were assigned to vascular modulation (n = 10), depot/formulation strategies (n = 23), ECM/stromal approaches (n = 17), ultrasound- or lymphatic-related approaches (n = 8), intratumoral immunotherapy (n = 11), or combination/multimodal strategies (n = 4). The evidence was predominantly preclinical (66/73; 90.4%) and used heterogeneous endpoints, precluding direct quantitative comparison. Current evidence supports several mechanistically distinct approaches to prolong local exposure, but comparative effectiveness and clinical translation remain uncertain. Future studies should standardize retention endpoints and integrate tumor persistence, systemic exposure, and safety.