Management of Peptide Receptor Radionuclide Therapy Toxicities in Neuroendocrine Neoplasm Patients

Peptide receptor radionuclide therapy (PRRT) has become an established treatment for patients with well-differentiated gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) that express somatostatin receptors. Among the available agents, lutetium-177 DOTATATE is the most commonly used radiolabeled somatostatin analog and has demonstrated significant clinical benefits, including improved response rates and prolonged progression-free survival, as shown in landmark trials such as NETTER-1 and NETTER-2. As the incidence of GEP-NENs continues to rise, the use of PRRT in clinical practice has grown accordingly. However, this therapy is associated with a range of toxicities that can affect multiple organ systems over different timeframes, including acute, subacute, and long-term periods. This review provides a comprehensive overview of the adverse effects associated with PRRT and presents evidence-based strategies for their monitoring, prevention, and management. This review also discusses the evolving paradigm of screening for clonal hematopoiesis before PRRT treatment, as well as the use of steroids as prophylaxis to prevent carcinoid crisis and bowel obstruction. A multidisciplinary approach is essential to ensure the safe delivery of treatment, early detection of complications, and tailored patient care. As clinical experience with PRRT expands, continued refinement of supportive care strategies will be critical to optimizing outcomes and minimizing toxicity in this complex patient population.