Abstract
Neuroendocrine tumours (NETs) are rare, biologically diverse neoplasms with a rising incidence due to improved diagnostics. Their management remains challenging, with multiple therapeutic strategies under evaluation. The present systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Literature searches were conducted across PubMed, Cochrane Library and ScienceDirect between January 2018 and July 2025. Eligible studies included randomized controlled trials, cohort studies and observational analyses involving adult patients with NETs. The primary outcomes were progression-free survival (PFS) and overall survival (OS). A total of 271 studies were screened and 22 met the inclusion criteria. Median PFS across therapies ranged between 2 and 23 months, whereas OS ranged between 9.6 and 60 months, depending on treatment type. Dual checkpoint inhibitors (nivolumab plus ipilimumab) demonstrated durable benefits, with OS time exceeding 55 months in some cohorts, whereas peptide receptor radionuclide therapy (PRRT) achieved a median PFS time of 22.8 months compared with 8.5 months for high-dose octreotide. Furthermore, targeted agents, such as sunitinib and nintedanib, improved PFS to ~11 months, with OS time extending beyond 30 months. Chemotherapy regimens such as CAPTEM yielded a PFS of 7-11 months. In conclusion, the present study revealed that NET therapies show heterogeneous but clinically meaningful benefits. PRRT, targeted therapy and combination regimens were revealed to be associated with the most durable outcomes, whereas immunotherapy demonstrated promise in selected patients. Tailored approaches remain crucial to optimize survival and quality of life of patients.