[18F]FDG Metabolic Tumor Volume as a Prognostic Marker in Neuroendocrine Neoplasm: A Multicenter Study

[¹⁸F]FDG PET/CT avidity predicts higher-grade disease and worse prognosis in patients with metastatic neuroendocrine neoplasm. However, there is less evidence regarding the role of [¹⁸F]FDG-avid tumor volume in predicting prognosis. We planned to determine whether metabolic tumor volume (MTV) on [¹⁸F]FDG PET/CT predicts prognosis in patients with advanced gastroenteropancreatic neuroendocrine neoplasm (GEPNEN). Methods: A multicenter retrospective study was performed on patients with advanced GEPNEN who underwent [¹⁸F]FDG PET/CT in a previously established cohort. Images were acquired across 3 centers using harmonized protocols and were contoured and verified at a flat SUV threshold of 4 using a semiautomated software workflow. The primary endpoint was overall survival. Patients were dichotomized into high- and low-MTV groups by the median value, with the overall survival of the 2 resulting cohorts compared by log-rank tests and multivariate analyses. Results: In total, 231 patients were included (49% male; median age, 60 y). In 45% of cases the primary was the pancreas, in 42% the small bowel, and in 13% another location. Regarding World Health Organization 2019 grade, 23% were grade 1, 52% grade 2, 21% grade 3, and 4% an unknown grade. The median follow-up was 27 mo (interquartile range, 11-49 mo), and median overall survival was 38.6 mo. Median overall survival was shorter in the high-MTV cohort than in the low-MTV cohort (cut point, 16.5 cm³; 23.8 mo vs. not reached; hazard ratio, 2.49; 95% CI, 1.69-3.66; P < 0.0001). Median time to treatment failure was also shorter in the high-MTV cohort (11.7 mo vs. 16.9 mo; hazard ratio, 1.52; 95% CI, 1.13-2.06; P = 0.005). Increasing histologic grade was associated with higher MTV (P = 0.0006, 1-way ANOVA). Multivariate analysis incorporating age, grade, sex, SUV_max, and MTV showed that only grade (P = 0.001) and MTV (P < 0.001) were independently prognostic. Conclusion: MTV is a prognostic biomarker in advanced GEPNEN. Reports of [¹⁸F]FDG PET in GEPNEN may benefit from comments on MTV in addition to the degree of [¹⁸F]FDG avidity.