Factors Driving Attrition from Neoadjuvant Therapy to Pancreatectomy in Localized Pancreatic Cancer

Neoadjuvant therapy (NAT) has become the cornerstone in the treatment of localized pancreatic cancer (LPC), with the goal of downstaging tumors, treating occult metastases, and selecting patients with favorable biology for surgery. Although the benefits of NAT have been well described, real-world data on attrition rates and barriers against proceeding to pancreatectomy are limited.

This study analyzed LPC patients treated with at least one cycle NAT at a high-volume center (2011-2022). The patients were stratified by radiographic stage (resectable [R], borderline resectable [BR], locally advanced [LA]), or pancreatectomy status. Reasons for attrition during NAT and survival outcomes were evaluated.

Among 427 LPC patients who received NAT (R, 57 [13%]; BR, 133 [31%]; and LA, 237 [56%]), 182 (43%) underwent pancreatectomy. The overall attrition rate of 57% during NAT was driven by disease progression (21%), persistent inoperability (22%), physiologic decline (11%), loss to follow-up evaluation (2%), and surgery refusal (1%). Attrition rates correlated with stage (R [23%], BR [44%], LA [73%]; p < 0.01). The median overall survival (OS) was significantly longer for the resected patients (30 vs 16 months; p < 0.01) and inversely correlated with stage (R [30 months], BR [21 months], and LA [18 months]; p < 0.01). Overall survival was similar across stages among the resected patients after NAT (R [31 months], BR [27 months], and LA [34 months]; p = 0.66).

Stage-stratified attrition during NAT remains a significant issue even for patients with R disease. The similar OS across stages for resected patients highlights NAT's role in selecting those most likely to benefit from surgery and underscores the need for strategies to reduce attrition.