Surgical Decision-Making in Pancreatic Ductal Adenocarcinoma

Abstract

Objective: To develop a predictive model of oncologic outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) undergoing resection after neoadjuvant or induction chemotherapy use. Background: Early recurrence following surgical resection for PDAC is common. The use of neoadjuvant chemotherapy prior to resection may increase the likelihood of long-term systemic disease control. Accurately characterizing an individual's likely oncologic outcome in the perioperative setting remains challenging. Methods: Data from patients with PDAC who received chemotherapy prior to pancreatectomy at a single high-volume institution between 2007 and 2018 were captured in a prospectively collected database. Core clinicopathologic data were reviewed for accuracy and survival data were abstracted from the electronic medical record and national databases. Cox-proportional regressions were used to model outcomes and develop an interactive prognostic tool for clinical decision-making. Results: A total of 581 patients were included with a median overall survival (OS) and recurrence-free survival (RFS) of 29.5 (26.5-32.5) and 16.6 (15.8-17.5) months, respectively. Multivariable analysis demonstrates OS and RFS were associated with type of chemotherapeutic used and the number of chemotherapy cycles received preoperatively. Additional factors contributing to survival models included: tumor grade, histopathologic response to therapy, nodal status, and administration of adjuvant chemotherapy. The models were validated using an iterative bootstrap method and with randomized cohort splitting. The models were well calibrated with concordance indices of 0.68 and 0.65 for the final OS and RFS models, respectively. Conclusion:We developed an intuitive and dynamic decision-making tool that can be useful in estimating OS, RFS, and location-specific disease recurrence rates. This prognostic tool may add value to patient care in discussing the benefits associated with surgical resection for PDAC.

Postoperative Chemotherapy is Associated with Improved Survival in Patients with Node‐Positive Pancreatic Ductal Adenocarcinoma After Neoadjuvant Therapy

“…Still, both the NCCN and ASCO clinical practice guidelines recommend clinicians consider administering postoperative chemotherapy after resection even if NAT was previously administered [24, 25]. In such circumstance, identifying patient populations likely to benefit from additional chemotherapy may prove helpful [32]. Like this study, van Roessel et al also noted a survival advantage associated with additional postoperative chemotherapy in patients with node‐positive disease [33].…”

Targeted therapy for pancreatic ductal adenocarcinoma: Mechanisms and clinical study

“…Furthermore, ESPAC‐5F trial demonstrated that neoadjuvant mFOLFIRINOX or gemcitabine plus capecitabine resulted in similar OS durations, and significantly better than neoadjuvant 50.4‐Gy capecitabine‐based chemoradiotherapy 256 . These clinical trials along with other studies question whether the addition of radiotherapy in NAT is beneficial or may actually be detrimental 4,177,257 . Consequently, given the lack of conclusive evidence on the effects of radiotherapy in NAT, we suggest that the use of radiotherapy in NAT should be limited to RCTs only.…”

“…Pancreatic ductal adenocarcinoma (PDAC) was the fourth leading cause of cancer‐related death in 2021 and is projected to be second by 2030 1,2 . It is associated with a poor 5‐year survival rate of 11%, most likely due to its tendency to disseminate early‐on, lack of effective systemic therapy, and delayed response 3–5 . Surgical resection is the only cure for PDAC currently, but patients often present with metastatic disease or unresectable primary tumors at diagnosis 6 .…”

Reshaping the Pancreatic Cancer Microenvironment at Different Stages with Chemotherapy

“…Overall survival (OS) and recurrence free survival (PFS) were associated with the number of chemotherapy cycles received preoperatively [54]. Patients with pancreatic cancer who received ≥67% of the recommended chemotherapy cycles or ≥56% cumulative relative dose intensity had improved OS [55].…”