March 06, 2026
A large, multi-institutional study led by Mayo Clinic Comprehensive Cancer Center investigators provides new insight on how treatment sequence can affect survival of patients in early-stage pancreatic ductal adenocarcinoma. Published in the Journal of the National Comprehensive Cancer Network, the research shows that patients whose tumors are considered up-front resectable may still benefit from chemotherapy before surgery. In particular, the study found that tumors in contact with a major vein near the pancreas were associated with worse outcomes when surgery was performed first. A difference that disappeared when chemotherapy was given before resection.
Rethinking traditional treatment pathways
Pancreatic cancer has long been approached through an anatomic lens, with treatment decisions guided by how closely a tumor involves nearby blood vessels. Under current National Comprehensive Cancer Network (NCCN) criteria, tumors with limited contact (≤ 180 degrees) with the portomesenteric vein are classified as up-front resectable, often leading clinicians to recommend immediate surgery followed by chemotherapy.
However, findings from this retrospective study challenge that long-standing approach. By analyzing outcomes from more than 1,400 patients treated across Mayo Clinic campuses in Minnesota, Arizona and Florida, investigators found that anatomy alone may not adequately capture risk, even in patients with early-stage disease.
"Many patients with early-stage pancreatic cancer undergo surgery first because it has historically been viewed as the best chance for cure," says Zhi Ven Fong, M.D., Dr.PH., a surgical oncologist at Mayo Clinic in Arizona and co–senior author of the study. "Our findings suggest that chemotherapy first, even in cases thought to be more straightforward, provides patients with the best opportunity for long-term survival."
Vein involvement highlights biologic risk
Approximately one-third of patients in the study had radiologic evidence of portomesenteric vein abutment at diagnosis. When all patients were analyzed together, overall survival appeared similar regardless of vein involvement. However, important differences emerged when treatment sequence was examined.
Among patients who underwent surgery first, those with vein abutment had significantly worse overall survival and lower rates of margin-negative (R0) resection compared with patients whose tumors did not contact the vein. In contrast, these differences were not observed in patients who received neoadjuvant chemotherapy before surgery, suggesting that chemotherapy mitigates the adverse impact of vein involvement.
These findings indicate that vein abutment may reflect more-aggressive tumor biology rather than simply a technical surgical challenge. Neoadjuvant chemotherapy likely improves outcomes by addressing micrometastatic disease early and increasing the likelihood of complete tumor removal.
"Our data confirm what we've seen in practice at Mayo Clinic for years," says Mark J. Truty, M.D., M.S., a surgical oncologist at Mayo Clinic in Minnesota and co-senior author. "The timing of surgery relative to chemotherapy is critically important for patient outcomes."
Implications for guidelines and clinical practice
Beyond individual patient outcomes, the study raises important questions about how pancreatic tumors are classified and managed. Current NCCN definitions group tumors with and without limited venous involvement into a single up-front resectable category, despite meaningful differences in prognosis and response to treatment.
"Our findings suggest that guidelines could be updated to reclassify tumors with any vein involvement as borderline resectable and to only include cancers with no vein involvement as up-front resectable," says Dr. Fong.
Notably, the study also found that more-aggressive surgical strategies, such as routine vein resection in patients treated with up-front surgery did not offset the negative impact of vein involvement on survival. This underscores the limitations of anatomy-based decision-making and reinforces the importance of systemic therapy early in the disease course.
Personalizing treatment decisions in pancreatic cancer care
Mayo Clinic has already adopted a chemotherapy-first approach for pancreatic cancer across stages, reflecting an emphasis on tumor biology, patient selection and multidisciplinary collaboration. The findings from this study provide enterprise-wide evidence supporting that strategy and offer a framework for refining national treatment standards.
"Our hope is that this study empowers both patients and clinicians to think carefully about treatment sequencing," says Dr. Truty. "We want people to know they have options and that starting with chemotherapy may be the best path forward."
For more information
Tan PH, et al. Redefining upfront resectable pancreatic ductal adenocarcinoma: Should vein abutment matter? Journal of the National Comprehensive Cancer Network. 2026;24:27.
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