Repeat peptide receptor radionuclide therapy (PRRT) in 11 neuroendocrine tumor patients showed disease control in 54.5% at first restaging, with an acceptable safety profile but significantly shorter progression-free survival than initial PRRT (13.1 vs 25.4 months).
54.5% disease control rate after repeat PRRTRepeat peptide receptor radionuclide therapy still provided meaningful benefit, though PFS was significantly shorter (13.1 vs 25.4 months) than initial treatment
What the researchers found
Among 11 neuroendocrine tumor patients who received repeat PRRT after disease progression:
Efficacy after PRRT2 (at first restaging, 3-6 months):
- Partial response: 18.2% (2/11)
- Stable disease: 36.4% (4/11)
- Progressive disease: 27.3% (3/11)
- Died before restaging: 18.2% (2/11)
- Overall disease control rate: 54.5% (6/11)
Progression-free survival:
- PRRT1: 25.4 months median PFS
- PRRT2: 13.1 months median PFS
- Difference statistically significant (P = 0.0001)
Safety: No significant difference in hematological or renal toxicity rates between PRRT1 and PRRT2.
Why it matters
Neuroendocrine tumors are rare cancers with limited treatment options. PRRT is one of the most effective therapies, using peptides to deliver radiation precisely to tumor cells. When patients progress after initial PRRT, clinicians face a difficult decision: is it safe and worthwhile to repeat? Most data comes from European centers, so this US experience fills an important evidence gap. The finding that repeat PRRT is safe and provides disease control in over half of patients gives clinicians a treatment option for this otherwise limited situation.
How the study worked
Retrospective single-center study using a longitudinal NET registry at a US NET center of excellence. 11 patients who received initial PRRT (either 177Lu-DOTATATE or 90Y-DOTATOC) followed by repeat PRRT after radiographic progression were identified. Patient, tumor, and treatment characteristics were reviewed. Objective response rates were assessed at first restaging (3-6 months). Short and long-term hematological and renal toxicities were compared between PRRT1 and PRRT2.
What this study cannot tell us
Very small sample size (n=11) severely limits the reliability of response rates and toxicity comparisons. Retrospective single-center design introduces selection bias. Different PRRT agents (177Lu-DOTATATE vs 90Y-DOTATOC) were used across patients, complicating comparisons. Two patients died before first restaging, which significantly affects the small-sample response calculations. The study cannot determine whether repeat PRRT extends overall survival compared to alternative treatments.
How to read the evidence
This is a small (n=11) retrospective single-center case series — among the lowest levels of clinical evidence. While it provides valuable real-world data from a US NET center of excellence, the findings should be considered hypothesis-generating rather than definitive. Larger prospective studies are needed.
When this study was published
Published in 2024, this is a recent contribution to the growing evidence on repeat PRRT, reflecting current clinical practice with both 177Lu-DOTATATE and 90Y-DOTATOC.
The bigger picture
PRRT represents one of the most successful applications of peptide-based targeted therapy in oncology. The radiolabeled somatostatin analog (a peptide) acts as a guided missile — binding to somatostatin receptors on tumor cells and delivering lethal radiation specifically to the cancer. As PRRT becomes more widely used globally, understanding when and how to repeat treatment is crucial. This study suggests repeat PRRT still provides benefit, though with diminishing returns, potentially due to changes in receptor expression or tumor biology.
Questions still open
- Can pre-treatment biomarkers or imaging predict which patients will benefit most from repeat PRRT?
- Would combining repeat PRRT with newer immunotherapy or targeted therapy improve outcomes?
- Is there a minimum interval between PRRT courses that optimizes efficacy of repeat treatment?
Common questions
What is peptide receptor radionuclide therapy (PRRT) and how does it work?
Why does the second round of PRRT work for a shorter time?
Read the original research
Repeat Peptide Receptor Radionuclide Therapy in Neuroendocrine Tumors: A NET Center of Excellence Experience.
Journal of gastrointestinal cancer, 55(3), 1165-1170
Citation
Grewal, Udhayvir S; Loeffler, Bradley T; Paschke, Alexander; Dillon, Joseph S; Chandrasekharan, Chandrikha. (2024). Repeat Peptide Receptor Radionuclide Therapy in Neuroendocrine Tumors: A NET Center of Excellence Experience.. Journal of gastrointestinal cancer, 55(3), 1165-1170. https://doi.org/10.1007/s12029-024-01065-z