PAST
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths in the US.(1) For localized, resectable disease, the current standard of multimodal care comprising surgery and chemotherapy improves disease-free survival (DFS) and overall survival (OS) compared to surgery alone.(2) The outcomes are worse in patients with poorly differentiated PDAC, which is associated with earlier recurrence and worse OS compared to well-differentiated tumors.(3) Literature on the timing of return to intended oncologic therapy (RIOT) in poorly differentiated PDAC is limited. Our study evaluates the optimal timing of RIOT in patients with poorly differentiated PDAC.
PRESENT
National Comprehensive Cancer Network guidelines on PDAC recommend initiation of adjuvant therapy within 12 weeks of surgery. In recent PDAC studies, earlier RIOT has not been consistently associated with a difference in OS.(4) These studies pool all patients with varying degrees of differentiation that may mask histology-specific treatment outcomes. Poorly differentiated PDAC has a more aggressive biology and shorter DFS compared to well or moderately differentiated PDAC.(3) The optimal timing of RIOT in this subgroup remains uncertain. Our study is unique as it focuses only on poorly differentiated PDAC patients. Using the National Cancer Database, we evaluated patients with poorly differentiated non-metastatic PDAC (2007–2016), who received upfront surgery followed by chemotherapy (n=3050 patients). Return to intended oncologic therapy within 9 weeks of surgery was associated with improved OS compared with RIOT after 9 weeks (HR 0.90, p = 0.032).(5) Similarly, RIOT within 7 weeks compared with RIOT after 7 weeks (HR 0.90, p = 0.039) and RIOT within 8 weeks compared with RIOT after 8 weeks (HR 0.89, p = 0.032) was associated with improved OS. In contrast, RIOT within 6 weeks was not associated with improved OS when compared with RIOT after 6 weeks (HR 0.96, p = 0.45). These findings suggest an optimal therapeutic window of <=9 weeks for RIOT in poorly differentiated PDAC patients.
FUTURE
Our study highlights the importance of timing of systemic therapy in patients with poorly differentiated PDAC. Timing of systemic therapy based on histologic differentiation may impact survival. Institutional and multi-institutional studies may help validate our findings from the National Cancer Database. Future studies focusing on poorly differentiated histology in PDAC patients may inform treatment decisions and impact survival. This subgroup deserves special attention due to its association with poor survival outcomes.
REFERENCES
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