Neutrophil-to-lymphocyte Ratio and CA 19.9 as Predictors of Perineural Invasion in Pancreatic Cancer

Pancreatic cancer has an incidence of 1,401,450 new cases diagnosed annually worldwide and is the third leading cause of cancer-related death in Spain. This disease is associated with a poor prognosis, reflected by a 5-year survival rate of less than 5% when all stages are grouped together.

Several prognostic factors for pancreatic cancer have been identified. The most relevant include preoperative levels of carbohydrate antigen 19-9 (CA 19.9), surgical margins after resection, venous and/or arterial vascular involvement, and histopathological features such as affected locoregional lymph nodes, or perineural and lymphovascular invasion. Among all these factors, perineural invasion may be the primary independent factor affecting prognosis, particularly in patients with relatively favorable pathological features.

The identification of perineural invasion before surgery could influence the clinical management of these patients. It may facilitate risk stratification, allowing the identification of patients who would benefit most from neoadjuvant treatments or more aggressive surgical procedures, such as vascular resections. However, perineural involvement is very difficult to detect preoperatively.

Only a few studies have analyzed the possible relationship between CA 19.9 and perineural invasion, and their results are inconsistent. Alternatively, some studies have demonstrated the utility of preoperative multidetector computed tomography in detecting extrapancreatic perineural invasion. However, these radiological tests are still not useful for directly detecting microscopic perineural invasion, especially in early stages.

On the other hand, in recent years, evidence has supported that the systemic inflammatory response may play an important role in the prognosis of different malignancies. Among these inflammatory markers, the neutrophil-to-lymphocyte ratio (NLR) has gained prominence. Regarding pancreatic cancer, many studies suggest that elevated preoperative NLR levels are associated with a worse prognosis. However, no studies have yet been published analyzing a possible relationship between this inflammatory marker and perineural invasion.

The main objective of this study is to correlate the neutrophil-to-lymphocyte ratio (NLR) and CA 19.9 with histopathologically confirmed perineural invasion and, in this way, investigate these data as potential preoperative markers of perineural invasion in pancreatic cancer. Our working hypothesis is that preoperative NLR and CA 19.9 are potential markers of perineural invasion.

As secondary objectives, we aim to study the effect of neoadjuvant therapy on inflammatory markers (NLR) and tumor markers (CEA and CA 19.9) in pancreatic cancer.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer, Adult; CA 19.9; Perineural Invasion; Neutrophil-to-Lymphocyte Ratio

• Study Type: Observational
• Enrollment (Estimated): 323

Contacts and Locations

• Study Contact: Name: Pau Plá Sánchez; Phone Number: 34 620541910; Email: paups88@gmail.com

Study Locations

• Spain
  • Las Palmas
    • Las Palmas de Gran Canaria, Las Palmas, Spain, 35010
      • Recruiting
      • University Hospital of Gran Canaria Doctor Negrín
      • Contact: Pau Plá Sánchez; Phone Number: 34 620541910; Email: paups88@gmail.com
      • Principal Investigator: Pau Plá Sánchez

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with pancreatic cancer and operated on between January 2020 and December 2024 from the participating centers who meet all the inclusion criteria and none of the exclusion criteria will be included.

Description

Inclusion Criteria:

• Patient with a histopathological diagnosis of adenocarcinoma.
• Surgical resection of the neoplasm.
• Preoperative blood count allowing calculation of the neutrophil-to-lymphocyte ratio and preoperative CA 19.9, both before and after neoadjuvant therapy.

Exclusion Criteria:

• Patients with a diagnosis of another histological type.
• Patients with incomplete data.
• Patients who were not operated on.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perineural invasion	The correlation between the preoperative neutrophil-to-lymphocyte ratio (NLR) and CA 19.9 with the presence of histopathologically confirmed perineural invasion in patients with pancreatic cancer	Within 30 days prior to surgery (for NLR and CA 19.9) and immediately following surgery for histopathological confirmation

Collaborators and Investigators

• Sponsor: University of Las Palmas de Gran Canaria

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): September 30, 2025

Study Registration Dates

• First Submitted: December 18, 2024
• First Submitted That Met QC Criteria: December 20, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 20, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: pancreatic cancer; Neutrophil-to-Lymphocyte Ratio; perineural invasion; CA 19.9
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: 2024-260-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No