18F-FDG PET is Superior to WHO Grading as a Prognostic Tool in Neuroendocrine Neoplasms and Useful in Guiding PRRT: A Prospective 10-Year Follow-up Study

Abstract

Accurate grading of patients with neuroendocrine neoplasms (NENs) is essential for risk stratification and optimal choice of therapy. Currently, grading is based on histologically assessed degree of tumor proliferation. The aim of the present study was to assess the long-term prognostic value of ¹⁸F-FDG PET imaging for risk stratification of NENs and compare it with tumor grading (World Health Organization 2010 classification). Methods: We conducted a prospective cohort study evaluating the prognostic value of ¹⁸F-FDG PET imaging and compared it with histologic grading. Enrolled were 166 patients of all grades and with histologically confirmed NENs of gastroenteropancreatic origin. The primary endpoint was overall survival (OS). Progression-free survival (PFS) was a secondary endpoint. In addition, OS in relation to peptide receptor radionuclide therapy (PRRT) was analyzed as an exploratory endpoint. The median follow-up time was 9.8 y. Results: Analysis of the whole cohort revealed that a positive ¹⁸F-FDG PET scan was associated with a shorter OS than a negative ¹⁸F-FDG PET scan (hazard ratio: 3.8; 95% CI: 2.4-5.9; P < 0.001). In G1 and G2 patients (n = 140), a positive ¹⁸F-FDG PET scan was the only identifier of high risk for death (hazard ratio: 3.6; 95% CI, 2.2-5.9; P < 0.001). In multivariate analysis, ¹⁸F-FDG PET, G3 tumor, ≥2 liver metastases, and ≥2 prior therapies were independent prognostic factors for OS, and ¹⁸F-FDG PET, G3 tumor, and ≥3 liver metastases were independent prognostic factors for PFS. For patients receiving PRRT, ¹⁸F-FDG-negative cases had a significantly longer survival than ¹⁸F-FDG-positive cases, whereas no difference was identified for tumor grading. ¹⁸F-FDG-positive patients receiving PRRT had a significantly longer median survival than patients not receiving PRRT (4.4 vs. 1.4 y, P = 0.001), whereas no difference was seen for ¹⁸F-FDG-negative patients. Conclusion:¹⁸F-FDG PET is useful for risk stratification of all NEN grades and is superior to histologic grading. ¹⁸F-FDG PET could differentiate G1 and G2 tumors into low- and high-risk groups. In the selection of therapy and for risk stratification of NEN patients, ¹⁸F-FDG PET status should be considered.

Keywords: 18F-FDG PET; Ki-67; neuroendocrine tumors; peptide receptor radionuclide therapy (PRRT); prognosis; prospective study.