Safety and Efficacy of PSMA-RLT in Early-Stage and Hormone-Sensitive Prostate Cancer

Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) is a novel treatment for patients with castration-resistant prostate cancer (CRPC), as it has a low toxicity profile and yields high prostate-specific antigen (PSA) responses. While PSMA-RLT is typically used during later disease stages, patients in earlier disease stages are likely to benefit from [¹⁷⁷Lu]Lu-PSMA (¹⁷⁷Lu-PSMA)- or [²²⁵Ac]Ac-PSMA (²²⁵Ac-PSMA)-radioligand treatment. A new retrospective study analyzed the safety and efficacy or PSMA-RLT in patients with early-stage and hormone-sensitive metastatic prostate cancer.

The study comprised patients with early-stage metastatic prostate cancer who had been treated with ¹⁷⁷Lu-PSMA and/or ²²⁵Ac-PSMA previously. Of the 20 patients included in the study, 18 received ¹⁷⁷Lu-PSMA-radioligand treatment and 2 received tandem treatment with both ¹⁷⁷Lu-PSMA and ²²⁵Ac-PSMA radioligands.

The primary outcome of the study was progression-free survival (PFS) after PSMA-RLT and toxicity according to the Common Terminology Criteria for Adverse Events. Secondary outcomes were PSA response and date of onset of CRPC state. Patients received a median of 2 treatment cycles (range, 1-6 cycles) and a median activity of 6.2 GBq ¹⁷⁷Lu-PSMA per cycle (interquartile range, 5.2-7.4 GBq).

PSMA-RLT treatment was well-tolerated overall in the patient group. The most common grade 1-2 side effects were dry mouth (n=6) and fatigue (n=8), which were only temporarily reported. One patient who received ²²⁵Ac-PSMA developed grade 3-4 bone marrow toxicity, and 1 patient developed CRPC 9 months following PSMA-RLT. The median PFS was 12 months (95% CI, 4.09-19.90 months). A total of 17 (85%) patients had a ≥50% PSA response after PSMA-RLT treatment.

This small cohort study demonstrated the safety and efficacy of PSMA-RLT treatment for patients with metastasized early-stage and hormone-sensitive prostate cancer. Additional studies should be carried out using larger cohorts and long-term follow-up to further investigate these findings.