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

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.

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.

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).

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.