PSMA-targeted radioligand therapy in prostate cancer: current status and future prospects

The prostate-specific membrane antigen (PSMA) targeted radioligand therapy (PRLT) for the treatment of metastatic castration-resistant prostate cancer (mCRPC) patients has generated significant interest among the oncologic community, with several publications documenting good response rates and survival benefits with low toxicity profiles.

Indications, patient preparation, dose administration, post-treatment imaging, dosimetry, and side effect profiles of ¹⁷⁷Lu-PSMA-617 are discussed in this article. We also discuss results from prospective studies, major retrospective studies, meta-analyses, clinical trials, and mentioned major ongoing clinical trials on PRLT. We have also portrayed our own experiences and future perspectives on PRLT.

For PRLT, PSMA-617 and PSMA-I&T molecules have revolutionized the theranostic approach in the management of advanced prostate cancer, with solid backing from several published articles showing favorable outcomes and an excellent safety profile of ¹⁷⁷Lu-PSMA-617. Improvement in quality of life and survival was seen in the majority of mCRPC patients after ¹⁷⁷Lu-PSMA-617 PRLT. Patients with good performance status, asymptomatic, only lymph node metastases, high PSMA expressing lesions, and no discordant FDG avid lesions have a longer survival after 177Lu-PSMA-617 PRLT than patients with poor performance status, symptomatic, hepatic, brain, and skeletal metastases, discordant PSMA, and FDG-avid lesions. Docetaxel and cabazitaxel are approved treatments for mCRPC patients. ¹⁷⁷Lu-PSMA-617 is approved as a third-line systemic treatment for mCRPC patients with failure to respond to androgen receptor pathway inhibitors and docetaxel therapy. PRLT is a safe and effective alternative to cabazitaxel (third-line systemic treatment), but it has a higher cost. ¹⁷⁷Lu-PSMA-617 could be a more efficient therapeutic option for mCRPC patients as first-line or combined therapy, and it may be a useful therapeutic option for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) patients. Several clinical studies and clinical trials on PRLT are currently underway. In the future, the results of these trials will be helpful in evolving treatment strategies for prostate cancer patients.