Total Neoadjuvant Therapy for Operable Pancreatic Cancer

Overall survival (OS) for operable pancreatic cancer (PC) is optimized when 4-6 months of nonsurgical therapy is combined with pancreatectomy. Because surgery renders the delivery of postoperative therapy uncertain, total neoadjuvant therapy (TNT) is gaining popularity.

We performed a retrospective cohort study of patients with operable PC and compared TNT with shorter course neoadjuvant therapy (SNT). Primary outcomes of interest included completion of neoadjuvant therapy (NT) and resection of the primary tumor, receipt of 5 months of nonsurgical therapy, and median OS.

We reviewed 541 consecutive patients from 2009 to 2019 including 226 (42%) with resectable PC and 315 (58%) with borderline resectable (BLR) PC. The median age was 66 years (IQR [59, 72]), and 260 (48%) patients were female. TNT was administered to 89 (16%) patients and SNT was administered to 452 (84%). Both groups were equally likely to complete intended NT and surgery (p = 0.90). Patients who received TNT and surgical resection were more likely to have a complete pathologic response (8% vs 4%, p < 0.01) and were more likely to receive at least 5 months of nonsurgical therapy (67% vs 45%, p < 0.01). The median OS was 26 months [IQR (15, 57)]; not reached among patients treated with TNT, and 25 months [IQR (15, 56)] among patients treated with SNT (p = 0.19).

TNT ensures the delivery of intended systemic therapy prior to a complicated operation without decreasing the chance of successful surgery; a window of operability was not lost. Patients who can tolerate SNT will likely benefit from TNT.