Implications of Perineural Invasion on Disease Recurrence and Survival After Pancreatectomy for Pancreatic Head Ductal Adenocarcinoma

Abstract

Objective: To describe PNI and to evaluate its impact on disease-free (DFS) and overall survival (OS) in patients with resected pancreatic ductal adenocarcinoma (PDAC). Summary of Background Data: Although PNI is a prognostic factor for survival in many GI cancers, there is limited knowledge regarding its impact on tumor recurrence, especially in ''early stage disease'' (PDAC ≤20 mm, R0/ N0 PDAC). Methods: This multicenter retrospective study included patients undergoing PDAC resection between 2009 and 2014. The association of PNI with DFS and OS was analyzed using Cox proportional-hazards models. Results: PNI was found in 87% of 778 patients included in the study, with lower rates in PDAC ≤20 mm (78.7%) and in R0/N0 tumors (70.6%). PNI rate did not differ between patients who underwent neoadjuvant therapy and upfront surgery (88% vs 84%, P = 0.08). Although not significant at multivariate analysis (P = 0.07), patients with PNI had worse DFS at univariate analysis (median DFS: 20 vs 15 months, P < 0.01). PNI was the only independent predictor of DFS in R0/N0 tumors (hazard ratio [HR]: 2.2) and in PDAC ≤ 20 mm (HR: 1.8). PNI was an independent predictor of OS in the entire cohort (27 vs 50 months, P = 0.01), together with G3 tumors, pN1 status, carbohydrate antigen (CA) 19.9 > 37 and pain. Conclusions: PNI represents a major determinant of tumor recurrence and patients' survival in pancreatic cancer. The role of PNI is particularly relevant in early stages, supporting the hypothesis that invasion of nerves by cancer cells has a driving role in pancreatic cancer progression.

Cellular and molecular mechanisms of perineural invasion of pancreatic ductal adenocarcinoma

“…A number of retrospective studies have shown that the postoperative survival rate of PDAC patients was negatively correlated with nerve infiltration [ 10 , 98 ‐ 101 ] (Table 3 ). One recent multicenter retrospective study enrolling 778 PDAC patients who received surgical treatment between 2009 and 2014 showed that the rate of PNI was 87% among these patients (T0/1, 61.6%; T2, 86.7%; T3/4, 90.1%; N0, 72.5%; and N1, 93.0%) [ 102 ]. PNI was an independent risk factor for disease‐free survival (DFS) and/or OS ( P < 0.0001) [ 103 ], and could serve as a prognostic indicator [ 99 , 104 , 105 ].…”

Preoperative Prognostic Nutritional Index and Systemic Immune-Inflammation Index for Predicting the Long-Term Recurrence-Free Survival of Patients with High-Risk Non-Muscle-Invasive Bladder Cancer After Transurethral Resection of a Bladder Tumour: A Cohort Study

“…Albumin concentration and lymphocyte count, which are the common indicators of nutritional status, are important predictors of nutritional risk and postoperative complications. PNI, which is calculated using serum albumin concentration and absolute lymphocyte count, is considered an essential predictive indicator of different types of human cancers [24,25,26]. As a hallmark of cancer that fosters recurrence, progression and metastasis, tumour-associated systemic in ammation has been extensively reviewed in recent years [27].…”

Intraductal Papillary Mucinous Carcinoma Versus Conventional Pancreatic Ductal Adenocarcinoma: A Comprehensive Review of Clinical-Pathological Features, Outcomes, and Molecular Insights

“…Using a more accurate matching process, based on a previously described nomogram for resected pancreatic cancer [57], Yopp et al [42] found a significantly superior survival in IPMC (the 5-year OS of 68% versus 23% in cPDAC). However, this study did not include vascular invasion and perineural invasion, which are two main accepted prognostic factors for resected cPDAC [58,59], in matching parameters. Contrarily, in the study by Duconseil et al [60], patients were matched by perineural invasion, tumor stage, lymph node ratio, and margin status and no statistical differences in survival were observed.…”