Exceptional Response to Multimodal Therapy in Stage IV Pancreatic Ductal Adenocarcinoma: A Case Report and Review

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a dismal prognosis, frequently presenting with metastatic disease that drives its lethality. Conventional chemotherapy offers limited survival benefits, prompting exploration of novel treatment strategies, including metastasis-directed therapies (MDT) for oligometastatic PDAC, characterized by a limited number of metastatic lesions. We describe a 74-year-old woman with KRAS G12D-mutated PDAC and 5 liver metastases, exceeding typical oligometastatic criteria (≤3 lesions). Systemic therapy with modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (modified FOLFIRINOX), followed by maintenance fluorouracil, leucovorin, and irinotecan (FOLFIRI), led to a partial response that induced an oligometastatic state. She subsequently underwent a multimodal non-surgical treatment sequence involving percutaneous microwave ablation (MWA) for hepatic metastases and stereotactic body radiotherapy (SBRT) to the primary pancreatic tumor, achieving complete radiologic resolution of all lesions. This yielded an exceptional ongoing 20-month progression-free survival, remarkable for a KRAS G12D-mutated PDAC, a subtype known for its challenging clinical course. Our literature review suggests that MDT, including percutaneous ablation techniques and SBRT, may improve outcomes in oligometastatic PDAC by enhancing local control and potentially by eliciting systemic immune-mediated effects. This case highlights the transformative potential of integrating tailored MDT with chemotherapy to deliver outstanding outcomes in select patients with advanced PDAC, though further research is needed to refine patient selection and optimize therapeutic approaches.