Radioactive Peptide Therapy Controls Disease in 64% of Patients with Aggressive Neuroendocrine Cancers

The researchers conducted a systematic review and meta-analysis searching PubMed and Embase for all clinical studies published through March 2025. They included studies of patients with grade 3 GEP-NEN treated with radiolabeled somatostatin analogs. Response was evaluated using RECIST 1.1 criteria (the standard method for measuring tumor response). Funnel plot analysis indicated no publication bias. Some studies also stratified patients by Ki-67 values, a marker of tumor aggressiveness.

High-grade (G3) neuroendocrine neoplasms have historically been considered too aggressive for PRRT, which was initially approved mainly for well-differentiated, lower-grade tumors. This meta-analysis provides the strongest pooled evidence to date that PRRT can still benefit these sicker patients — a 64% disease control rate and median survival of nearly 2.5 years are clinically meaningful results for a cancer with few effective options.

PRRT with Lutathera (¹⁷⁷Lu-DOTATATE) was a breakthrough for neuroendocrine tumors when it won FDA approval in 2018, but that approval was based largely on low-to-intermediate grade tumors. The field has been debating whether high-grade tumors — which are more aggressive and have variable somatostatin receptor expression — would also benefit. This meta-analysis strengthens the case for expanding PRRT use to these patients and may influence future treatment guidelines.

Only 7 studies met inclusion criteria, with a total of 317 patients — relatively small for a meta-analysis. All studies were retrospective or observational (no randomized controlled trials). There was variability in treatment protocols, patient selection, and how outcomes were measured. Only 3 studies fully reported overall survival data. The heterogeneity in Ki-67 cutoffs and tumor differentiation within the G3 category could mask important differences in response.