¹⁸F-FDG-PET is superior to WHO grading as prognostic tool in neuroendocrine neoplasms and useful in guiding peptide receptor radionuclide therapy: a prospective 10-year follow-up study of 166 patients

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 (WHO) 2010 classification). Methods: We conducted a prospective cohort study evaluating the prognostic value of ¹⁸F-FDG-PET imaging and compared it to histological grading. Enrolled were 166 patients of all grades and with histologically confirmed NENs of gastro-entero-pancreatic 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 years. Results: Analysis of the whole cohort revealed that a positive ¹⁸F-FDG-PET was associated with a shorter OS than a negative ¹⁸F-FDG-PET (Hazard Ratio (HR): 3.8; 95% Confidence interval (CI): 2.4 – 5.9; P < 0.001). In G1 and G2 patients (n = 140) a positive ¹⁸F-FDG-PET was the only identifier of high-risk for death (HR: 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 the ¹⁸F-FDG-positive, whereas no difference was identified for tumor grading. ¹⁸F-FDG-positive patients receiving PRRT had a significantly longer median survival compared to patients not receiving PRRT (4.4 vs 1.4 years, 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 histological 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.