PRRT for well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs)

Neuroendocrine tumors (NETs) are rare, heterogeneous neoplasms with varying prognoses and management approaches. Peptide receptor radionuclide therapy (PRRT), targeting tumors expressing somatostatin receptors, delivers cytotoxic radiation to tumor cells. While PRRT has demonstrated efficacy in advanced, well-differentiated NETs, the optimal sequencing with other therapies remains an area of active research. This review explores PRRT's role in NET management, focusing on its mechanisms, clinical efficacy, safety profile, and integration into a multi-modal treatment strategy. We also examine evidence on the sequencing of PRRT with surgery, liver-directed therapy, chemotherapy, and targeted therapies to optimize treatment outcomes. We conducted a comprehensive review of recent clinical trials, cohort studies, and expert consensus guidelines to assess PRRT's place in the treatment paradigm. Factors influencing treatment sequencing, such as tumor type, receptor expression, disease burden, and patient-specific characteristics, are also discussed. PRRT has proven effective for patients with advanced, somatostatin receptor-positive NETs, especially for inoperable tumors or those progressing after other therapies. While PRRT plays a vital role in management, its sequencing with other treatments remains complex, with evidence supporting its use both early and late in treatment based on individual patient factors. Optimizing its sequencing with other treatments requires further research but offers potential for improved outcomes. A personalized, multidisciplinary approach is essential for maximizing PRRT's benefits in NET management. This review article summarizes current evidence and describes patient-specific circumstances, enabling treatment provider to make informed PRRT sequencing decisions.