Somatostatin receptor PET tumor burden biomarkers in PRRT-treated neuroendocrine tumors: prognostic evidence, clinical implications, and methodological challenges

Peptide receptor radionuclide therapy (PRRT) is an established treatment for patients with advanced somatostatin receptor (SSTR)-positive neuroendocrine tumors (NETs), but treatment outcomes remain heterogeneous. Quantitative SSTR PET/CT biomarkers, including SSTR-expressing tumor volume (SSTR-TV) and total lesion SSTR expression (TL-SSTR), may improve prognostication by capturing whole-body receptor-positive tumor burden and global receptor expression. This narrative review summarizes the available clinical evidence on volumetric SSTR PET biomarkers in NET patients undergoing PRRT, with emphasis on baseline tumor burden, composite receptor-expression metrics, conventional uptake parameters, and serial PET changes during treatment. Across 13 clinical studies including approximately 633 patients, higher baseline SSTR-TV was frequently associated with shorter progression-free or overall survival, although findings were not uniform across cohorts. Evidence for TL-SSTR was more limited and less consistently reported. Several small, methodologically heterogeneous studies suggest that early reductions in SSTR-TV or TL-SSTR during PRRT may help identify patients with more favorable outcomes, but this evidence remains limited by small sample sizes, variable interim imaging schedules, non-standardized cut-offs, and selection bias.