Systematic Review Suggests Early [¹⁷⁷Lu]Lu-DOTATATE PRRT Improves GEP-NET Resectability and Survival
Background
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are often aggressive, with current guidelines approving peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin analogues like [¹⁷⁷Lu]Lu-DOTATATE as a second-line treatment for progressive disease. This approach targets somatostatin receptors (SSTRs), which are highly expressed on NET cells. However, the current second-line positioning means patients may experience significant disease progression before receiving PRRT, limiting its full therapeutic potential. There's a critical need to explore earlier interventions to improve patient outcomes, particularly in cases of unresectable or advanced disease.
Study Design
Researchers conducted a systematic review following PRISMA guidelines to evaluate the role of neoadjuvant, adjuvant, or first-line PRRT in GEP-NETs. The search spanned PubMed and clinicaltrials.gov up to May 31, 2025, identifying 25 eligible papers. These included case reports, original papers, and clinical trial protocols. Data extracted from each paper covered clinical setting, patient characteristics, treatment regimen (including [¹⁷⁷Lu]Lu-DOTATATE), and oncologic and surgical outcomes, focusing on tumor response, resectability, and survival benefits.
Results
Preliminary data from the reviewed studies, comprising case reports, retrospective, and prospective cohorts, strongly suggest a beneficial role for early PRRT. Neoadjuvant PRRT was shown to induce tumor shrinkage, regress vascular involvement, and convert unresectable disease to resectable in up to 45% of patients. Reported objective response rates reached as high as 70%, significantly improving surgical feasibility. A promising survival benefit was observed, particularly in patients who received PRRT before surgery.
Preliminary results from the
NETTER-2trial further support [¹⁷⁷Lu]Lu-DOTATATE as a first-line therapy forSSTR-positive G2-G3 GEP-NETs, demonstrating significant improvement in progression-free survival. Conversely, the review found a lack of evidence supporting the adjuvant use of PRRT in GEP-NETs.
Key Findings
- Neoadjuvant PRRT converted up to 45% of unresectable GEP-NETs to resectable disease.
- Objective response rates reached up to 70% with early PRRT in GEP-NET patients.
- The
NETTER-2trial supports first-line [¹⁷⁷Lu]Lu-DOTATATE for G2-G3 GEP-NETs, improving progression-free survival. - Early PRRT shows promising survival benefits, especially when administered pre-surgery.
- Evidence for adjuvant PRRT in GEP-NETs is currently lacking.
Why It Matters
This systematic review highlights a potential paradigm shift for GEP-NET management, moving [¹⁷⁷Lu]Lu-DOTATATE PRRT from a second-line option to earlier neoadjuvant or first-line settings. Implementing PRRT earlier could significantly improve resectability rates and overall survival for GEP-NET patients, especially those with initially unresectable tumors. This suggests that clinicians might consider PRRT as a primary or pre-surgical intervention, potentially allowing more patients to undergo curative surgery. While promising, specific patient selection criteria, optimal dosing, and timing protocols still require validation through further prospective, randomized studies before widespread clinical adoption.
prrt
dotatate
gep-net
neuroendocrine-tumors
somatostatin-analog
systematic-review