Neoadjuvant Therapy Improves Survival in Upfront Resectable PDAC Subtype

Neoadjuvant therapy improves survival outcomes for patients with upfront resectable pancreatic ductal adenocarcinoma and vein abutment, according to data from a Mayo Clinic multi-institutional study published in the Journal of the National Comprehensive Cancer Network (NCCN).¹ The research suggested that the current NCCN guidelines, which classify tumors with 180 degrees or less of portomesenteric vein (PMV) abutment as "upfront resectable," may lead to suboptimal treatment sequencing. By receiving chemotherapy prior to surgical intervention, patients with even minor vein involvement can achieve survival rates comparable with those who have no vein involvement at all.

Clinical Efficacy

The study analyzed 1446 patients who underwent pancreatoduodenectomy for upfront resectable pancreatic ductal adenocarcinoma between 2002 and 2023 across 3 Mayo Clinic sites. The median overall survival (OS) was 28.8 months in patients who underwent PMV abutment vs 31.2 months in those who did not (P = .17). Among those who underwent upfront surgery, PMV abutment was identified as a significantly poor prognostic factor. This cohort demonstrated a median OS of 19.2 months, a contrast to the 27.6 months observed in patients without any vein involvement (P <.05). Furthermore, the negative-margin (R0) resection rate for those with vein abutment following upfront surgery was significantly lower at 63.1%, compared with 87.2% for those without abutment (P < .05).

The administration of neoadjuvant therapy effectively mitigated these survival and surgical disparities. Patients with PMV abutment who received preoperative chemotherapy achieved a median OS of 42.5 months, while those without abutment reached 51.6 months (P = .48). In the modern chemotherapy era of patients treated since 2017, the survival benefit was even more pronounced; patients without PMV abutment saw a median OS of 45 months vs 20.4 months in patients with PMV abutment with upfront surgery (P <.05). Among patients who received neoadjuvant therapy, a significant difference was also not observed, with a median OS of 50.4 months vs 60.0 months (P = .72). The R0 resection rate for the neoadjuvant cohort remained high at 91.4% for those with abutment compared with 94.0% without abutment, demonstrating the regimen's ability to clear surgical margins effectively.

“Many patients with early-stage pancreatic cancer undergo surgery first because it is historically believed to be the best chance for cure,” stated Zhi Ven Fong, MD, MPH, DrPH, a surgical oncologist at Mayo Clinic in Arizona and co-senior author of the study, in a press release on the results.² “Our findings suggest that chemotherapy first, even in cases thought to be more straightforward, provides patients with the best opportunity for long-term survival.”

Study Design

The study utilized a retrospective, multi-institutional design involving all patients from 3 Mayo Clinic sites who underwent pancreatoduodenectomy for nonmetastatic, upfront resectable pancreatic ductal adenocarcinoma as defined by NCCN criteria—no more than 180° PMV abutment without contour irregularity. Patients with any arterial involvement were excluded. The cohort was stratified by the presence or absence of PMV abutment and further sorted by treatment sequence: upfront surgery vs neoadjuvant therapy. Neoadjuvant regimens primarily consisted of multi-agent chemotherapy, such as gemcitabine plus nab-paclitaxel. The primary end point was OS, with R0 resection rates and pathologic tumor characteristics as secondary end points.

Safety and Pathologic Outcomes

Safety and technical success were assessed through surgical and pathologic outcomes. Neoadjuvant therapy was associated with a reduction in pathologic tumor size in the no PMV abutment group, which was a median of 3.0 cm vs 3.5 cm in the PMV abutment group. Although 35.6% of the PMV abutment cohort required PMV resection, the study noted that this aggressive surgical approach did not independently confer a survival benefit; rather, the biological response to chemotherapy was the primary driver of improved outcomes.

Mark Truty, MD, a surgical oncologist at Mayo Clinic in Minnesota and co-senior author, emphasized the clinical implications of these findings for patient counseling. “Our hope is that this study empowers both patients and clinicians to think carefully about treatment sequencing. We want people to know they have options, and that starting with chemotherapy may be the best path forward,” he stated.²

References

1. Tan PH, Thiels CA, Poruk K, et al. Redefining upfront resectable pancreatic ductal adenocarcinoma: should vein abutment matter? J Natl Compr Canc Netw. 2026;24(2):27-33. doi:10.6004/jnccn.2025.7097
2. Corey C. Mayo Clinic study finds chemotherapy before surgery improves survival in early-stage pancreatic cancer. News release. Mayo Clinic News Network. February 9, 2026. Accessed February 16, 2026. https://tinyurl.com/ypkywf63