Can Peptide-Targeted Radiation Therapy Still Help Patients with Rare Thyroid Cancer in the Era of New Targeted Drugs? | Research

The takeaway

Peptide receptor radionuclide therapy may still have a role for medullary thyroid carcinoma patients who lack RET mutations and have limited treatment options, but its clinical value remains unproven.

Limited options for RET-negative MTC
While RET inhibitors have transformed treatment for RET-mutated medullary thyroid carcinoma, patients without RET mutations face few effective systemic therapies — positioning PRRT as a potential but unproven option for this underserved group.

What the researchers found

Peptide receptor radionuclide therapy (PRRT) remains a potential treatment option for medullary thyroid carcinoma, particularly for patients with RET-negative recurrent or metastatic disease who have limited systemic therapy options. However, its clinical utility in the RET inhibitor era is uncertain. Highly selective RET inhibitors have proven efficacy with low toxicity for RET-mutated MTC, and multikinase inhibitors are available but limited by resistance and side effects. PRRT's role is now most relevant for the subset of patients who cannot benefit from RET-targeted therapy.

Why it matters

Medullary thyroid carcinoma patients without RET mutations face a difficult treatment landscape — multikinase inhibitors often cause significant side effects or stop working due to resistance. PRRT, which uses radiolabeled peptides to deliver targeted radiation directly to tumor cells via peptide receptors, could fill an important niche for these underserved patients if its efficacy can be better established.

How the study worked

Narrative review evaluating the published evidence on peptide receptor radionuclide therapy in medullary thyroid carcinoma, including discussion of its limitations in the context of newly approved RET inhibitors and existing multikinase inhibitor therapies.

Who was studied

Patients with persistent, recurrent, or metastatic medullary thyroid carcinoma, with particular focus on RET-negative disease

What this study cannot tell us

As a narrative review, the article does not apply systematic search methodology or meta-analysis. The evidence base for PRRT in MTC specifically is limited, with small case series rather than large randomized trials. The abstract does not report specific response rates or survival data for PRRT in MTC. The review acknowledges that PRRT's clinical utility 'remains under investigation.'

How to read the evidence

This is a narrative review article that discusses the current evidence for PRRT in MTC. The underlying evidence base for PRRT in this specific cancer is limited to small case series, not large clinical trials. The review provides expert opinion and contextual analysis rather than new data.

When this study was published

Published in 2025, this is a timely review that places PRRT in the context of recently approved RET inhibitors, making it highly relevant to current clinical decision-making in medullary thyroid carcinoma.

The bigger picture

The treatment landscape for medullary thyroid carcinoma has been transformed by selective RET inhibitors like selpercatinib and pralsetinib. This shift narrows PRRT's potential patient population to those with RET-negative disease — a smaller but still underserved group. The review reflects a broader trend in oncology where new targeted therapies continually reshape the role of older treatment modalities, requiring periodic reassessment of their clinical value.

Questions still open

What proportion of medullary thyroid carcinoma patients are RET-negative and thus potential candidates for PRRT?
Could PRRT be combined with RET inhibitors or other systemic therapies for enhanced efficacy in resistant or advanced MTC?
What somatostatin receptor subtypes are expressed on MTC cells, and does receptor expression predict PRRT response?

Common questions

What is peptide receptor radionuclide therapy (PRRT) and how does it work?

PRRT is a targeted radiation treatment that uses small peptides labeled with radioactive atoms. These peptides are designed to bind to specific receptors on tumor cells. Once attached, the radioactive label delivers radiation directly to the cancer cells while largely sparing surrounding healthy tissue. It's like a guided missile for tumors that express the right receptors.

Why has PRRT's role changed for this type of thyroid cancer?

New drugs called RET inhibitors have proven highly effective for the majority of medullary thyroid carcinoma patients who have RET mutations. Before these drugs existed, PRRT was one of few options for advanced disease. Now, PRRT's potential role is mainly limited to the subset of patients whose tumors lack RET mutations and who don't respond well to other available treatments.

Read the original research

Is peptide receptor radionuclide therapy still a promising option for medullary thyroid carcinoma?

Endocrine, 87(3), 943-950

View on PubMed ↗Publisher’s paper ↗

Citation

de Andrade, Fernanda Accioly; Bulzico, Daniel; Corbo, Rossana; Vaisman, Fernanda. (2025). Is peptide receptor radionuclide therapy still a promising option for medullary thyroid carcinoma?. Endocrine, 87(3), 943-950. https://doi.org/10.1007/s12020-024-04114-6