Computed tomography-guided percutaneous biopsy for assessing tumor heterogeneity in neuroendocrine tumor metastases to the liver.

Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) frequently metastasize to the liver, with heterogeneity in tumor grade impacting patient prognosis and treatment. The Ki-67 index, a key prognostic marker, often varies between primary and metastatic sites; however, routine liver biopsy remains controversial. Although percutaneous computed tomography-guided core needle biopsy (PCT-CNB) is safe and effective for focal lesions, its role in detecting intertumor grading discrepancies and survival implications in GEP-NETs is underexplored. Conflicting survival associations with grade shifts have been reported in previous studies. We hypothesized that PCT-CNB could identify clinically significant grading heterogeneity in liver metastases, correlating with survival outcomes, thereby refining risk stratification and therapeutic strategies.

Aim: To investigate intertumor grading heterogeneity in GEP-NET liver metastases via PCT-CNB.

Methods: We retrospectively investigated 92 patients with liver metastases from GEP-NETs via PCT-CNB, 76 patient samples from the liver and primary sites, and 16 from the liver and secondary liver sites. Ki-67 immunohistochemistry was performed for tissue sampling, and grading classifications were determined. Intertumor grading classification heterogeneity and associated changes in patient survival outcomes were also evaluated.

Results: No procedure-related mortality was recorded during or after biopsy. In 37/92 patients (40.2%), the grading classifications changed: The grading increased from G1 to G2 in 13 patients, from G1 to G3 in 2, and from G2 to G3 in 14; the grading decreased from G2 to G1 in 5 patients, from G3 to G1 in 1, and from G3 to G2 in 2. Patients with G1 or G2 disease had better progression-free survival and overall survival (OS) outcomes than those with G3 disease did (P = 0.001 and P < 0.001, respectively). The 5-year and 10-year OS rates for stable G2 patients were 67.5% and 26.0%, respectively, decreasing to 46.4% and 23.2%, respectively, among G2 patients whose grade increased (P = 0.016).

Conclusion: The PCT-CNB of liver metastases from GEP-NETs differed in grade between the liver tumor and primary site/secondary liver metastases. Additionally, when grading increased from G2, the OS rate significantly decreased.