Association of Neoadjuvant Therapy on Pathologic and Clinical Outcomes for Pancreatic Adenocarcinoma.

[INTRODUCTION] The use of total neoadjuvant chemotherapy (TNC) for pancreatic adenocarcinoma (PDAC) is increasing. This study evaluated the association between chemotherapy timing [TNC, perioperative (PERIOP), adjuvant (ADJ)] and total duration of chemotherapy on survival in PDAC.

[METHODS] Single-institution, retrospective study (2020-2023) of PDAC patients that underwent surgical resection and chemotherapy with an intended 6-mo course. We compared overall survival and chemotherapy completion rates between TNC, PERIOP, and ADJ groups.

[RESULTS] Of 115 patients, 10 received TNC, 69 PERIOP, and 36 ADJ chemotherapy. Pancreaticoduodenectomy was performed in 64.4% of patients. Resectable disease was more common in the ADJ group (97.2%) compared to PERIOP (47.8%) or TNC (30.0%, P < 0.01) groups, with vascular resection more common in TNC compared to PERIOP or ADJ groups (40.0% versus 7.2% versus 8.3%, P = 0.02). The TNC group was more frequently node negative (70.0% versus 43.5% PERIOP versus 36.1% ADJ, P = 0.02). Median survival from first treatment was similar between the groups (TNC 43 versus PERIOP 40 versus ADJ 38 mo, P = 0.70). By definition, all TNC patients completed 6 mo of chemotherapy. Completion of chemotherapy was much less common in the in the PERIOP group (40.6%) and the ADJ group (36.1%, P < 0.01), as patients were unable to tolerate chemotherapy after surgery. Patients who completed 6 mo of chemotherapy, regardless of timing relative to surgery, had a median overall survival of 43 mo compared to 35 mo in those who did not (hazard ratio 0.37, 95% confidence interval: 0.19-0.73; P < 0.01).

[CONCLUSIONS] Completion of 6 mo of chemotherapy was associated with improved survival, regardless of timing. As postoperative completion rates remain low, TNC may facilitate higher chemotherapy completion rates.