Objective: Unresectable pancreatic ductal adenocarcinoma carries a dismal prognosis, and conventional chemoradiotherapy offers limited survival benefits. This review aims to systematically evaluate the efficacy, safety, and synergistic potential of local ablation techniques and their combination with systemic therapies for unresectable pancreatic cancer, based on evidence published between 2020 and 2025.

Methods: A comprehensive literature search was conducted using PubMed, Web of Science, CNKI, and Wanfang databases for studies published from 2020 to 2025. Keywords included "unresectable pancreatic cancer," "ablation," "radiofrequency ablation (RFA)," "microwave ablation (MWA)," "cryoablation," "high-intensity focused ultrasound (HIFU)," "irreversible electroporation (IRE)," "iodine-125 seed implantation," and "combined therapy." The inclusion criteria encompassed clinical trials, retrospective studies, and meta-analyses. A total of 28 studies were selected for final analysis to summarize the application and outcomes of various local ablative modalities and their integrated strategies.

Results: Thermal ablation techniques, including RFA, MWA, HIFU, and cryoablation, demonstrated variable efficacy. RFA, the most common method, achieved a median overall survival (OS) of 5-25 months but with a complication rate of 4-22%. Cryoablation showed a favorable safety profile (e.g., 4% acute pancreatitis) with a median OS of 5-16.2 months. Among non-thermal techniques, IRE was particularly notable for treating tumors near vital vasculature, reporting a median OS of up to 24.9 months, which improved to a 53.5% 2-year OS when combined with chemotherapy. Iodine-125 seed implantation provided effective local control (88.46%) and a median OS of 15.3 months. Combination therapies revealed significant synergies. The integration of cryoablation with iodine-125 seeds significantly extended median OS to 16.2 months compared to cryoablation alone (8.4 months). Furthermore, combining ablation (cryoablation or IRE) with immunotherapy or chemotherapy (e.g., gemcitabine) enhanced clinical outcomes, yielding median OS of 13 months and 11.8-14.2 months, respectively, without a substantial increase in toxicity.

Conclusion: Local ablation modalities, especially IRE and cryoablation, alone or combined with iodine-125 seeds, chemotherapy, or immunotherapy, provide promising local tumor control, pain relief, and survival extension for patients with unresectable pancreatic cancer. The synergistic effects of combined regimens highlight a paradigm shift towards multimodal management. However, the current evidence is largely based on single-center, retrospective studies, underscoring the need for standardized protocols and future multicenter randomized controlled trials to validate these findings and optimize treatment strategies.