Multimodality therapy in metastatic pancreas cancer with a BRCAmutation and durable long-term outcome: biology, intervention, or both?

ABSTRACTMetastatic pancreatic adenocarcinoma (PDAC) is a rapidly lethal disease, with less than half of patients surviving 12 months, and 5-year survival approximately 3%. These outcomes are in large part due to a lack of effective medical and surgical therapies for metastatic PDAC. Herein, we present the case of a patient with oligometastatic liver recurrence of BRCA2-mutated PDAC following a curative-intent resection. Through a combination of systemic chemotherapy, metastasectomy, radiotherapy, and subsequent targeted therapy with olaparib, the patient is asymptomatic four years following metastatic diagnosis with stable low-volume disease. This patient’s excellent outcome is attributable to the multi-disciplinary care received, all aspects of which were informed by new evidence surrounding metastasectomy for metastatic PDAC, the unique biology and medical treatment of BRCA-mutated PDAC, and the role of radiotherapy in controlling locoregional recurrence. We provide a review of this evidence, while highlighting the importance of evaluating disease biology through somatic and germline genetic testing as well as monitoring response to systemic chemotherapy.