Peptide Receptor Radionuclide Therapy (PRRT) combination strategies with diverse agents enhance neuroendocrine tumor management.

For patients with neuroendocrine tumors (NETs), systemic treatment is evolving, yet current Peptide Receptor Radionuclide Therapy (PRRT) with agents like 177Lu-DOTATATE, while a cornerstone for well-differentiated, somatostatin receptor-expressing (SSTR+) metastatic NETs, rarely achieves complete responses or sustained progression-free survival. This gap highlights the critical need for enhanced therapeutic approaches. Combining PRRT with other antitumor agents is crucial to augment its efficacy and overcome resistance mechanisms without significantly increasing toxicity, thereby improving long-term patient outcomes.

This comprehensive review systematically explored various combination strategies involving Peptide Receptor Radionuclide Therapy (PRRT) for neuroendocrine tumors (NETs). It analyzed existing literature and ongoing clinical trials, focusing on fundamental mechanisms driving synergistic effects. Protocols for combined PRRT approaches were discussed, including combinations with somatostatin analogs (SSAs), radiosensitizing/cytotoxic chemotherapy, different therapeutic isotopes, transarterial radioembolization (TARE), targeted molecular drugs, and immune-checkpoint inhibitors (ICIs). Neoadjuvant PRRT before surgery was also considered, aiming to provide practical insights for clinicians.