Is there a role for early SSTR-targeting PRRT in GEP-NET?

Area of Science:

• Oncology
• Nuclear Medicine

Background:

• Peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin analogues like [¹⁷⁷Lu]Lu-DOTATATE is approved for progressive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) as second-line treatment.
• Emerging evidence suggests PRRT may have a role in earlier treatment settings for GEP-NETs.

Purpose of the Study:

• To systematically review the literature on neoadjuvant, adjuvant, or first-line PRRT in GEP-NETs.
• To evaluate the clinical utility and outcomes of PRRT in earlier treatment settings.

Main Methods:

• A systematic review adhering to PRISMA guidelines was performed.
• Searches of PubMed and clinicaltrials.gov identified 25 eligible studies (case reports, original papers, clinical trial protocols).
• Data extracted included clinical setting, patient characteristics, treatment, and oncologic/surgical outcomes.

Main Results:

• Neoadjuvant PRRT demonstrated tumor shrinkage and conversion to resectable disease in up to 45% of patients, with objective response rates up to 70%.
• PRRT before surgery showed improved feasibility, promising survival benefits, and high response rates.
• The NETTER-2 trial supports first-line [¹⁷⁷Lu]Lu-DOTATATE for SSTR-positive G2-G3 GEP-NETs, improving progression-free survival; evidence for adjuvant use is lacking.

Conclusions:

• PRRT may be a valuable option in neoadjuvant and first-line settings for selected GEP-NET patients, enhancing resectability and survival.
• Further prospective, randomized studies are essential to establish optimal selection criteria, timing, and long-term impact.