# Serum β-hCG as a Biomarker in Pancreatic Neuroendocrine Tumors: Rethinking Single-Analyte Approach

## TL;DR

Serum β-hCG is a promising and affordable biomarker for monitoring aggressive pancreatic neuroendocrine tumors.

## Contribution

Identifies serum β-hCG as a novel, cost-effective biomarker for pancreatic neuroendocrine tumors.

## Key findings

- β-hCG levels correlate with aggressive tumor behavior, including progressive disease and higher tumor grade.
- β-hCG concentrations increased consistently over time, especially in more aggressive tumors.
- β-hCG shows potential as a monitoring tool until more advanced assays become widely available.

## Abstract

The lack of biomarkers in neuroendocrine tumors (NETs) represents a critical unmet need. Conventional single analytes lack the required diagnostic accuracy. Multianalyte assays (e.g., NETest) offer improved performance but remain costly and largely unavailable. In our study, serum beta-human chorionic gonadotropin (β-hCG) shows promise as a biomarker in metastatic pancreatic NETs. β-hCG concentrations strongly correlate with established indicators of aggressive tumor behavior, including progressive disease, per RECIST; greater liver tumor burden; and higher WHO tumor grade. Throughout the study period, β-hCG levels increased consistently, with sharper rises noted in more aggressive tumors. As a widely available and inexpensive assay, serum β-hCG emerges as a useful tool for the evaluation of treatment response and disease monitoring in pancreatic NETs, especially in the transitional period until multianalyte assays become a mainstay in scientific guidelines.

Despite recent advances, neuroendocrine tumors (NETs) remain a challenging topic, due to their diversity and the lack of suitable biomarkers. Multianalyte assays and the shift to an omics-based approach improve on the conventional single-analyte strategy, albeit with their own drawbacks. We explored the potential of serum β-hCG as a biomarker for NETs and discussed its role in disease monitoring. We recruited 40 patients with non-functioning pancreatic NETs, all with liver metastases. Serum β-hCG concentrations were measured at 3-month intervals over 48 months. We performed a comparative and a repeated measures analysis of β-hCG depending on WHO grade (G1, G2), liver tumor burden (LTB; below 10%, 10–25%), and RECIST 1.1. (stable disease, progressive disease). Patients with progressive disease (p < 0.001), 10–25% LTB (p < 0.001) and WHO Grade 2 (p < 0.001) displayed higher β-hCG concentrations. Throughout the study, β-hCG concentrations consistently increased across the entire cohort. Delta β-hCG during the study period was greater in patients with 10–25% LTB (p < 0.001), progressive disease (p < 0.001), and G2 (p = 0.003). Serum β-hCG correlates with established indicators of malignancy and disease progression in metastatic NETs, supporting further studies as a monitoring and prognostic biomarker. Despite promising results from novel biomarkers, there is still a place for single-analyte assays in NETs.