Journal: Asian journal of andrology
This publication is a narrative review of lutetium-177–labeled PSMA radioligand therapy for prostate cancer, with a focus on metastatic castration-resistant disease.
Key points:
- Clinical context: Prostate cancer that progresses to castration-resistant disease has limited benefit from conventional systemic treatments and poor prognosis. This has driven interest in targeted radionuclide approaches.
- Therapeutic agent: The review centers on 177Lu-PSMA radioligands, especially 177Lu-PSMA-617, highlighted as the most advanced and promising PSMA-targeted radioligand therapy currently in clinical use and approved in 2022.
- Efficacy overview: The authors summarize recent clinical data showing that 177Lu-PSMA therapy can provide meaningful antitumor activity in metastatic castration-resistant prostate cancer (mCRPC), improving disease control in patients who have typically exhausted standard options.
- Safety profile: The review discusses safety evaluations indicating that 177Lu-PSMA is generally manageable from a toxicity standpoint, while still requiring careful monitoring and management of treatment-related adverse effects.
- Limitations and open questions:
- Extension of use: How and whether to extend use beyond mCRPC into earlier or non–castration-resistant settings.
- Treatment sequencing: Optimal sequencing with other systemic therapies (androgen receptor–targeted agents, chemotherapy, PARP inhibitors, etc.).
- Biomarkers and imaging: Need for standardized imaging and molecular biomarkers to select patients, monitor response, and harmonize practice.
- Toxicity management: Further refinement in toxicity prediction and management.
- Future directions: The authors call for prospective studies to define treatment algorithms, validate biomarkers, clarify long-term outcomes, and optimize integration of PSMA-targeted radioligand therapy into the broader therapeutic landscape.
Overall, the article positions 177Lu-PSMA-617 as a major advance for mCRPC while emphasizing that key aspects of patient selection, timing, and broader application remain to be established.