Total Neoadjuvant Therapy for Pancreatic Adenocarcinoma

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Patients with pancreatic adenocarcinoma who underwent total neoadjuvant therapy, consisting of chemotherapy followed by chemoradiation prior to surgery, had improved overall survival compared with those who had single-agent neoadjuvant therapy or surgery first, according to a large cohort study presented during the virtual edition of the 2020 Society of Surgical Oncology (SSO) International Conference on Surgical Cancer Care.1 Patients receiving total neoadjuvant therapy also had “more profound pathologic responses,” reported the study’s lead author, Eileen O’Halloran, MD, MS, of Fox Chase Cancer Center, Philadelphia.

“Consideration of neoadjuvant therapy has become the norm” for many patients with pancreatic adenocarcinoma, Dr. Halloran noted. “There is limited evidence recommending specific neoadjuvant therapy regimens off study, and practices vary with regard to the use of chemotherapy and chemoradiation. Many experts advocate for using both in a total neoadjuvant therapy approach.”

Retrospective Review

“We performed a retrospective review of all patients with pancreatic adenocarcinoma at our National Cancer Institute–designated cancer center over a 20-year period who underwent total pancreatoduodenectomy and had pre- and postoperative treatment data available,” Dr. Halloran explained. “We defined total neoadjuvant therapy as at least 6 weeks of neoadjuvant chemotherapy and either 5.5 weeks of intensity-modulated radiation therapy or stereotactic modulated radiation therapy in the preoperative setting.”

“Total neoadjuvant therapy may offer improved short- and long-term outcomes for patients with pancreatic adenocarcinoma….”
— Eileen O’Halloran, MD, MS

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Of the 358 patients meeting the criteria, 168 underwent the surgery-first approach, 111 received single-agent neoadjuvant therapy, and 79 received total neoadjuvant therapy. “As expected, the majority of the surgery-first and single-agent groups went on to receive additional adjuvant therapy, whereas the majority of those receiving total neoadjuvant therapy did not,” Dr. O’Halloran stated.

“The only demographic and clinical pathologic differences in the groups were that the patients who received total neoadjuvant therapy more frequently had coronary artery disease and hyperlipidemia. Unsurprisingly, this group had a higher proportion of borderline resectable and locally advanced disease than the other groups. They also had a more advanced clinical stage than the other groups.”

‘Lower Pathologic Stage’

Patients who received total neoadjuvant therapy “exhibited a lower pathologic stage on final pathology,” Dr. O’Halloran noted. In addition, 10% had a complete pathologic response. None of the patients in the other two groups achieved a pathologic complete response.

“Margins were negative more frequently in the total neoadjuvant therapy group,” Dr. O’Halloran noted, with 86.1% having negative margins, compared with 71% in the single-agent group and 72% in the surgery-first group. Patients who received total neoadjuvant therapy were, however, more likely to have vascular resection during surgery.

Significantly more patients were downstaged in the total neoadjuvant therapy group than in the single-agent group (75.6% vs 46.3%). Patients in the total neoadjuvant therapy group were less likely to have adjuvant therapy, 39.2% vs 55.9% in the single-agent group and 76.8% in the surgery-first group.

“On multivariable analysis controlling for stage, margin positivity, and receipt of adjuvant chemotherapy, patients who received total neoadjuvant therapy demonstrated improved overall survival” compared with the other two groups (hazard ratio = 0.67, = .028),” the investigators reported. Based on the findings of improved overall survival and more profound pathologic responses, they concluded: “Total neoadjuvant therapy may offer improved short- and long-term outcomes for patients with pancreatic adenocarcinoma while simultaneously offering the benefit of selecting patients for surgery based on fitness and tumor biology.” 

DISCLOSURE: Dr. O’Halloran reported no conflicts of interest.


1. O’Halloran EA, Lefton M, Rhodes L, et al: Total neoadjuvant therapy offers improved survival and pathologic response in pancreatic adenocarcinoma. 2020 SSO International Conference on Surgical Cancer Care. Abstract 55.