Defining the Optimal Duration of Neoadjuvant Therapy for Pancreatic Ductal Adenocarcinoma: Time for a Personalized Approach?

Despite recent advances, pancreatic ductal adenocarcinoma (PDAC) continues to be associated with dismal outcomes, with a cure evading most patients. While historic treatment for PDAC has been surgical resection followed by 6 months of adjuvant therapy, there has been a recent shift toward neoadjuvant treatment (NAT). Several considerations support this approach, including the characteristic early systemic spread of PDAC, and the morbidity often surrounding pancreatic resection, which can delay recovery and preclude patients from starting adjuvant treatment. The addition of NAT has been suggested to improve margin-negative resection rates, decrease lymph node positivity, and potentially translate to improved survival. Conversely, complications and disease progression can occur during preoperative treatment, potentially eliminating the chance of curative resection. As NAT utilization has increased, treatment durations have been found to vary widely between institutions with an optimal duration remaining undefined. In this review, we assess the existing literature on NAT for PDAC, reviewing treatment durations reported across retrospective case series and prospective clinical trials to establish currently used approaches and seek the optimal duration. We also analyze markers of treatment response and review the potential for personalized approaches that may help clarify this important treatment question and move NAT toward a more standardized approach.