A meta-analysis of 317 patients found that peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin analogs achieved a 64% disease control rate and nearly 30 months median survival in high-grade neuroendocrine cancers.
64%disease control rate achieved by PRRT in high-grade neuroendocrine cancers — tumors previously considered too aggressive for this therapy
What the researchers found
Across 7 studies totaling 317 patients with grade 3 (G3) gastro-entero-pancreatic neuroendocrine neoplasms:
- Objective response rate (ORR): 34% (95% CI: 22–46%) — meaning about one-third of patients had measurable tumor shrinkage
- Disease control rate (DCR): 64% (95% CI: 52–76%) — meaning nearly two-thirds had their disease stabilize or shrink
- Median progression-free survival: 13.88 months (95% CI: 10.33–18.64)
- Median overall survival: 29.95 months (95% CI: 19.80–45.30)
The treatments used were [¹⁷⁷Lu]Lu-DOTA-TATE and/or [⁹⁰Y]Y-SSA, which are radioactive versions of somatostatin analog peptides that target receptors on tumor cells.
Why it matters
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.
How the study worked
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.
What this study cannot tell us
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.
How to read the evidence
This is a systematic review and meta-analysis, which sits high in the evidence hierarchy. However, it is based on observational studies rather than randomized controlled trials, and the total patient count of 317 is modest. The evidence is strong for supporting PRRT's role but not definitive without RCT confirmation.
When this study was published
Published in 2026 with literature searches through March 2025, this is the most current meta-analysis available on PRRT for high-grade neuroendocrine tumors.
The bigger picture
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.
Questions still open
- Which specific subgroups of high-grade neuroendocrine tumor patients benefit most from PRRT — those with higher or lower Ki-67 values?
- How does PRRT compare to chemotherapy as first-line treatment for grade 3 neuroendocrine neoplasms?
- Would combining PRRT with other therapies like checkpoint inhibitors improve outcomes in high-grade tumors?
Common questions
What is PRRT and how does it work?
Why were high-grade tumors thought to be poor candidates for PRRT?
Read the original research
Peptide receptor radionuclide therapy (PRRT) in high grade neuroendocrine neoplasms: a systematic review and meta-analysis.
European journal of nuclear medicine and molecular imaging
Citation
Zampella, Emilia; Piscopo, Leandra; Green, Roberta; Cantoni, Valeria; Nappi, Carmela; Gaudieri, Valeria; Caiazzo, Elisa; Scaglione, Mariano; Cuocolo, Alberto; Klain, Michele. (2026). Peptide receptor radionuclide therapy (PRRT) in high grade neuroendocrine neoplasms: a systematic review and meta-analysis.. European journal of nuclear medicine and molecular imaging. https://doi.org/10.1007/s00259-025-07726-w