¹⁷⁷Lu-PSMA therapy in patients with prostate cancer. “Holiday” strategy. Pilot study

Aim. To evaluate the strategy of temporary interruption of prostate-specific membrane antigen (PSMA)-targeted therapy ¹⁷⁷Lu-PSMA.

Materials and methods. A retrospective observational study was conducted which included 30 patients divided into two groups: treatment group (n = 16) received 2 to 4 fractions of ¹⁷⁷Lu-PSMA and switched to observation (“holiday”), and control group (n = 14) completed the standard 6 fractions. Prostate-specific antigen (PSA) reduction rates, progression-free survival (PFS), adverse event rate, and effect of combination therapy (¹⁷⁷Lu-PSMA + enzalutamide) were evaluated.

Results. In the first group, a decrease in PSA by more than 50 % was observed in 100 % of patients, in the second group in 92.3 %. The median PFS was 8 months in the first group and 6 months in the second. No serious adverse events (> grade II) were observed. Combination with enzalutamide was associated with improved PFS (median 12 months vs 6 months). Patients with poorly differentiated tumors (Gleason ≥9) and previous ²²³Ra therapy had worse prognosis (median PFS 5 months).

Conclusion. Interruption of ¹⁷⁷Lu-PSMA therapy after 2–4 fractions with subsequent continuation in case of progression is a promising strategy that allows balancing between efficacy and safety. This approach is especially relevant for patients with limited metastatic burden and high risk of hematological toxicity. However, given the limited and heterogeneous patient sample, a detailed study in a larger patient cohort is necessary.