Lymph Node Metastases, Additional Organ Resection Associated With Increased Recurrence Risk for PNETs


A study found a number of factors associated with increased recurrence risk for patients with locally advanced pancreatic neuroendocrine tumors following surgical resection, including sex, lymph node metastases, and resection of other organs with tumor involvement.

Both positive lymph node involvement and resection of organs with tumor involvement were associated with increased risk of recurrence for patients who previously underwent surgery for locally advanced pancreatic neuroendocrine tumors (PNETs), according to data published in JAMA Network Open.

The data interpretation found that, in general, these patients undergoing surgical resection have both excellent disease-free survival (DFS) rates and overall survival (OS) rates.

“The current study demonstrated that male sex, lymph node metastases, and resection of additional organs (but not blood vessels) were associated with an increased probability of tumor recurrence,” wrote the study investigators who were led by Ashley L. Titan, MD, wrote in their article. “Interestingly, functional tumors had a lower incidence of recurrence. Our findings support prior studies that have found that men are at a greater risk of disease recurrence postoperatively.”

Five-year DFS, which was the study’s primary end point, was 61% with the secondary end point of 5-year OS observed at a rate of 91% of at 5 years. Examining the patients who survived to last follow-up, 75 out of 91 patients had an ECOG performance status of 0 or less than or equal to 1.

A number of things wereFactors significantly associated with an increased risk of recurrence included lymph node involvement (HR, 7.66; 95% CI, 2.78-21.12; P <.001), additional organ resection (HR, 6.15; 95% CI, 1.61-23.55; P = .008), and male sex (HR, 3.77; 95% CI, 1.68-8.97; P = .003).

Of the 99 patients with locally advanced nondistant metastatic PNET examined in this study, 4 patients underwent preoperative neoadjuvant therapy. Moreover, 18 patients underwent had pancreaticoduodenectomy, 68 patients underwent distal or subtotal pancreatic resection, 10 patients underwent a total resection, and 3 patients underwent other pancreatic procedures.

There were additional organ resections necessary for 86 patients. The organs included were the spleen in 71 patients, major blood vessel in 17 patients, bowel in 2 patients), stomach in 4 patients), and kidney in 2 patients).

“Factors associated with tumor recurrence as well as overall survival have not been previously established for locally advanced tumors without metastatic disease,” wrote the investigators. “Locally advanced tumors may invade venous structures like the superior mesenteric vein and portal vein, and in these instances, they require resection and reconstruction, but in many instances the tumor only abuts the vein without invasion and can be dissected off with blunt and sharp dissection.”

This cohort of 99 patients undergoing surgically aggressive resections included 56 men (57%) with a mean age of 57 years. The mean follow-up was 5.3 years.

The investigators recognize that the lack of a control group of similar patients who did not undergo some type of surgery is a limitation of the data. Moreover, the team admits to a selection bias toward operative treatment of patients who underwent surgery because a complete pathological analysis of tumor extent leads to more meaningful survival data.

“This study’s findings suggest that patients with locally advanced PNETs without liver or distant metastases can have the tumor excised with acceptable rates of disease-free progression and mortality,” wrote the investigators concluded researchers.


Titan AL, Norton JA, Fisher AT, et al. Evaluation of outcomes following surgery for locally advanced pancreatic neuroendocrine tumors. JAMA Network Open. 2020;3(11):e2024318. doi:10.1001/jamanetworkopen.2020.24318.

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