A Novel Validated Recurrence Risk Score to Guide a Pragmatic Surveillance Strategy After Resection of Pancreatic Neuroendocrine Tumors

Abstract

Objective: Despite heterogeneous biology, similar surveillance schemas are utilized after resection of all pancreatic neuroendocrine tumors (PanNETs). Given concerns regarding excess radiation exposure and financial burden, our aim was to develop a prognostic score for disease recurrence to guide individually tailored surveillance strategies. Methods: All patients with primary nonfunctioning, nonmetastatic well/moderately differentiated PanNETs who underwent curative-intent resection at 9-institutions from 2000 to 2016 were included (n = 1006). A Recurrence Risk Score (RRS) was developed from a randomly selected derivation cohort comprised of 67% of patients and verified on the validation-cohort comprised of the remaining 33%. Results: On multivariable analysis, patients within the derivation cohort (n = 681) with symptomatic tumors (jaundice, pain, bleeding), tumors >2cm, Ki67 >3%, and lymph node (LN) (+) disease had increased recurrence. Each factor was assigned a score based on their weighted odds ratio that formed a RRS of 0 to 10: symptomatic = 1, tumor >2cm = 2, Ki67 3% to 20% = 1, Ki67 >20% = 6, LN (+) = 1. Patients were grouped into low- (RRS = 0–2; n = 247), intermediate-(RRS = 3–5; n = 204), or high (RRS = 6–10; n = 9)-risk groups. At 24 months, 33% of high RRS recurred, whereas only 2% of low and 14% of intermediate RRS recurred. This persisted in the validation cohort (n = 325). Conclusions: This international, novel, internally validated RRS accurately stratifies recurrence-free survival for patients with resected PanNETs. Given their unique recurrence patterns, surveillance intervals of 12, 6, and 3 months are proposed for low, intermediate, and high RRS patients, respectively, to minimize radiation exposure and optimize cost/resource utilization.

Incidence and impact of Textbook Outcome among patients undergoing resection of pancreatic neuroendocrine tumors: Results of the US Neuroendocrine Tumor Study Group

“…Depending on tumor location, size, and proximity to the pancreatic duct, resection may include pancreatoduodenectomy (PD), distal pancreatectomy (DP), or enucleation (EN). In the absence of recurrence, PNETs have a relatively good prognosis compared with other gastrointestinal tumors with a 5‐year survival up to 85% 2‐5 …”

Predicting survival in non‐functional pancreatic neuroendocrine tumours

“…Similarly, recent studies have reported poor prognosis in some of the well-differentiated NF-PNETs and factors including tumour grade G2, Ki67 index, lymph node metastasis, perineural invasion and tumour diameter were demonstrated to be associated with recurrence and death. 14,16 However, the European Neuroendocrine Tumor Society guidelines do not recommend adjuvant treatment after surgical resection for these patients 17 and no standard surveillance programmes have been constructed. The results from our data showed that patients with age >52 years and tumour grade G2 were more likely to die after surgical resection.…”

Clinical and Molecular Risk Factors for Recurrence Following Radical Surgery of Well-Differentiated Pancreatic Neuroendocrine Tumors

“…The presence of hormone clinical syndrome in F-PanNET favors early diagnosis and thus surgical resection at early stages. However, for patients with NF-PanNETs the presence of symptoms at diagnosis is usually related to tumor mass effect or tumoral infiltration on the surrounding structures and therefore is associated with worse prognosis (21,22). To date, because of the recent increased incidental diagnosis of small NF-PanNETs, fewer patients present with symptoms at diagnosis (23).…”

“…Conversely, PNI is a distinct pathologic entity observable in the absence of LVI. The rate of LVI and PNI in PanNETs rages from 22-36% to 17-39%, respectively (9,14,22,32). Vascular and lymphatic vessels and nerves can potentially be a route of metastatic spread to regional lymph nodes and distant organs and are therefore considered a histologic indicator of aggressive tumor behavior.…”

“…Vascular and lymphatic vessels and nerves can potentially be a route of metastatic spread to regional lymph nodes and distant organs and are therefore considered a histologic indicator of aggressive tumor behavior. Indeed, the presence of LVI is associated with an x4-8 and PNI x2-6 risk of recurrence (9,15,22). Because PanNET recurrence is rare, multivariable analysis of predictive factors is often challenging.…”